Bladder Cancer

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A Phase II/III Trial of MEDI4736 (Durvalumab) and Chemotherapy for Patients With High Grade Upper Tract Urothelial Cancer Prior to Nephroureterectomy


Condition: Renal Pelvis and Ureter Urothelial Carcinoma

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT04628767

Sponsor: National Cancer Institute (NCI)

Phase: Phase 3

Eligibility:

  • Age: minimum 18 Years maximum N/A
  • Gender: All

Inclusion Criteria:

  • STEP 1 REGISTRATION AND RANDOMIZATION
  • Patient must have the ability to understand and the willingness to sign a written informed consent document. Patients with impaired decision-making capacity (IDMC) who have a legally authorized representative (LAR) or caregiver and/or family member available will also be considered eligible
  • Patient must have a diagnosis of high grade upper tract urothelial carcinoma proven by biopsy within 60 days prior to registration with one of the following:
  • Upper urinary tract mass on cross-sectional imaging or
  • Tumor directly visualized during upper urinary tract endoscopy before referral to medical oncology
  • NOTE: Biopsy is standard of care (SOC) and required for enrollment to study. This is vital for best practice
  • Leukocytes >= 3,000/mcL (obtained =< 14 days prior to registration)
  • Platelets >= 100,000/mcL (obtained =< 14 days prior to registration)
  • Total bilirubin =< 1.5 x institutional upper limit of normal (ULN) (or =< 2.5 x ULN for patients with Gilbert's disease) (obtained =< 14 days prior to registration)
  • Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional ULN (obtained =< 14 days prior to registration)
  • Hemoglobin (Hgb) >= 9 g/dL (obtained =< 14 days prior to registration)
  • NOTE: Packed red blood transfusion is allowed to achieve this parameter as per treating investigator
  • Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
  • NOTE: These patients must be stable on their anti-retroviral regimen with evidence of at least two undetectable viral loads within the past 6 months on the same regimen; the most recent undetectable viral load must be within the past 12 weeks. They must have a CD4 count of greater than 250 cells/mcL over the past 6 months on this same anti-retroviral regimen and must not have had a CD4 count < 200 cells/mcL over the past 2 years, unless it was deemed related to the cancer and/or chemotherapy induced bone marrow suppression. They must not be currently receiving prophylactic therapy for an opportunistic infection and must not have had an opportunistic infection within the past 6 months
  • NOTE: For patients who have received chemotherapy in the past 6 months, a CD4 count < 250 cells/mcL during chemotherapy is permitted as long as viral loads were undetectable during this same chemotherapy. They must have an undetectable viral load and a CD4 count >= 250 cells/mcL within 7 days of registration
  • For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
  • NOTE: Testing for HIV, hepatitis B or hepatitis C is not required unless clinically indicated
  • Patients with a history of hepatitis C virus (HCV) infection must have been treated and have undetectable viral load. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
  • Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better
  • Patient must have a body weight of > 30 kg
  • Patient must have a life expectancy of >= 12 weeks
  • Patient must have a creatinine clearance > 15 ml/min as by Crockroft-Gault or 24-hour creatinine clearance within 28 days prior to registration
  • NOTE: Patients will be assigned to cisplatin-ineligible and cisplatin-eligible cohorts based on their creatinine clearance, Eastern Cooperative Oncology Group (ECOG) performance status, and grade (if any) of peripheral neuropathy and hearing loss in keeping with SOC cisplatin contraindications. Patients that are cisplatin-eligible will be randomized to either Arm A or Arm B
  • Patients that meet the following criteria will be assigned to the cisplatin-ineligible Arm C:
  • Creatinine clearance of > 15 ml/min and =< 50 ml/min
  • Patient must have an absolute neutrophil count (ANC) >= 1,000/mcL obtained =< 14 days prior to registration
  • Patient must have ECOG performance status 0-2
  • Patients that meet the following criteria will be randomized to cisplatin-eligible Arm A or Arm B:
  • Patient must have an absolute neutrophil count (ANC) >= 1,500/mcL obtained =< 14 days prior to randomization
  • Patient must have ECOG performance status 0-1
  • Patient must have left ventricular ejection fraction (LVEF) >= 50% by (either multigated acquisition scan [MUGA] or 2-D echocardiogram) obtained within 28 days prior to randomization
  • Patient must not have peripheral neuropathy >= grade 2 or hearing loss >= grade 3

Exclusion Criteria:

  • Patients must not have any component of small cell carcinoma. Other variant histologic types are permitted provided the predominant (>= 50%) subtype is urothelial carcinoma
  • Patients must not be pregnant or breast-feeding due to the potential harm to an unborn fetus and possible risk for adverse events in nursing infants with the treatment regimens being used. All patients of childbearing potential must have a blood test or urine study within 14 days prior to registration to rule out pregnancy. A patient of childbearing potential is defined as any patient, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: 1) has achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy; or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)
  • Patients of childbearing potential and sexually active patients must not expect to conceive or father children by using accepted and effective method(s) of contraception or by abstaining from sexual intercourse from the time of registration, while on study treatment and for at least 6 months after the last dose of protocol treatment
  • Patient must have no evidence of metastatic disease or clinically enlarged lymph nodes (>= 1.0 cm short axis) on imaging required within 28 days prior to registration (solitary slightly enlarged lymph node with negative biopsy is allowed)
  • NOTE: Patients with elevated alkaline phosphatase, calcium or suspicious bone pain/tenderness should also undergo baseline bone scans to evaluate for bone metastasis
  • Patient must not have another active (or within 2 years) second malignancy other than resected non-melanoma skin cancers, resected in situ breast, cervical or other in situ carcinoma, and either clinically insignificant per the investigator (e.g. =< Gleason 3+4) on surveillance or previously treated prostate cancer with no rising prostate specific antigen (PSA) and no plan to treat
  • NOTE: Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial. Patients in whom concomitant or prior bladder/urethra predominant (>= 50%) urothelial carcinoma have been surgically resected and demonstrated to be only non-invasive cancer (< cT1N0) are eligible regardless of time elapsed
  • Patient must not have any uncontrolled illness including, but not limited to, ongoing or active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and tuberculosis [TB] testing in line with local practice), symptomatic congestive heart failure (CHF), myocardial infarction (MI) in last 3 months, or unstable angina pectoris, significant uncontrolled cardiac arrhythmia, liver cirrhosis, interstitial lung disease, or psychiatric illness/social situations that would limit compliance with study requirements
  • Patient must not have received prior radiation therapy to >= 25% of the bone marrow for other diseases
  • Patient must not have received prior systemic anthracycline therapy
  • NOTE: Patients who have received prior intravesical chemotherapy at any time for non-muscle invasive urothelial carcinoma of the bladder are eligible
  • Patient must not have an active autoimmune disease requiring immunosuppressive therapy within 2 years prior to registration or a history of inflammatory bowel disease (inflammatory bowel disease [IBD], colitis, or Crohn's disease), systemic lupus erythematosus, Sarcoidosis syndrome, Wegener syndrome or immune-related pneumonitis or interstitial lung disease. Patients with well-controlled hyper/hypothyroidism, celiac controlled by diet alone, diverticulosis, diabetes mellitus type I, vitiligo, alopecia, psoriasis, eczema, lichen planus, or similar skin/mucosa condition are eligible
  • Patient must not be on or have used immunosuppressive medication within 14 days prior to the first dose of MEDI4736 (MEDI4736 (durvalumab). The following are exceptions to this criterion:
  • Intranasal, inhaled, intra-auricular, topical steroids, or local steroid injections (e.g. intra-articular injection
  • Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent at the time of enrollment
  • Steroids as premedications for hypersensitivity reactions (e.g. computed tomography [CT] scan premedication)
  • Patient must not have a concomitant primary urothelial carcinoma of the bladder and/or urethra
  • NOTE: Patients in whom concomitant or prior bladder/urethra predominant (>= 50%) urothelial carcinoma have been surgically resected and demonstrated to be only non-invasive cancer (< cT1N0) are eligible regardless of time elapsed
  • Patient must not have prior history of muscle-invasive urothelial carcinoma with or without systemic chemotherapy (T2-4a and/or N1) within 2 years prior to registration
  • NOTE: Patients who have no evidence of disease (NED) for more than 2 years from the latest therapy (surgery, radiation, chemotherapy, or clinical trial) are eligible
  • Patient must not have received live attenuated vaccine within 30 days prior to the first dose of MEDI4736 (durvalumab), while on protocol treatment and within 30 days after the last dose of MEDI4736 (durvalumab)
  • Patient must not have had a major surgical procedure (as defined by the Investigator) within 28 days prior to registration
  • Patient must not have a history of allogenic organ transplantation

View trial on ClinicalTrials.gov


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A Phase 3b, Open-Label, Single-Arm, Multicenter Study to Assess the Feasibility of Home Instillation of UGN-102 for Treatment of Patients With Low-Grade (LG) Non-Muscle-Invasive Bladder Cancer (NMIBC) at Intermediate Risk (IR) of Recurrence


Condition: Bladder Cancer, Urothelial Carcinoma, Urothelial Carcinoma Bladder

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT05136898

Sponsor: UroGen Pharma Ltd.

Phase: Phase 3

Eligibility:

  • Age: minimum 18 Years maximum N/A
  • Gender: All

Inclusion Criteria:

  • 1. Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and the protocol. 2. Patient who has newly diagnosed or historic LG NMIBC (Ta) histologically confirmed by cold cup biopsy at Screening or within 8 weeks before Screening. 3. Has IR disease, defined as having 1 or 2 of the following:
  • presence of multiple tumors.
  • solitary tumor > 3 cm.
  • recurrence (≥ 1 occurrence of LG NMIBC within 1 year of the current diagnosis at the initial Screening Visit). 4. Negative voiding cytology for high-grade (HG) disease within 6 weeks before Screening. 5. Has adequate organ and bone marrow function as determined by routine laboratory tests as below:
  • Leukocytes ≥ 3,000/μL (≥ 3×10^9/L).
  • Absolute neutrophil count ≥ 1,500/μL (≥ 1.5×10^9/L).
  • Platelets ≥ 100,000/μL (≥ 100×10^9/L).
  • Hemoglobin ≥ 9.0 g/dL.
  • Total bilirubin ≤ 1.5 × upper limit of normal (ULN).
  • Aspartate aminotransferase (AST)/Alanine aminotransferase (ALT) ≤ 2.5 × ULN.
  • Alkaline phosphatase (ALP) ≤ 2.5 × ULN.
  • Estimated glomerular filtration rate (eGFR) ≥ 30 mL/min. 6. Has no evidence of active urinary tract infection (UTI) at the Screening and baseline visits. 7. Patient is willing to receive instillations of UGN-102 at home (ie, Treatment Visits 2 to 6) by an appropriately trained home health professional. 8. Contraceptive use by men and women should be consistent with local regulations regarding the methods of contraception for clinical study participants. Women of childbearing potential (defined as premenopausal women who have not been sterilized), including female patients and female partners of male patients, must be willing to use 2 acceptable forms of effective contraception from first instillation through 6 months post treatment. Acceptable methods of birth control that are considered to have a low failure rate (ie, less than 1% per year) when used consistently and correctly include implants, injections, combined (estrogen/progesterone) oral contraceptives, intrauterine devices (only hormonal), condoms with spermicide, sexual abstinence, or vasectomized partner. 9. Has an anticipated life expectancy of at least the duration of the trial.

Exclusion Criteria:

  • 1. Received Bacillus Calmette-Guérin (BCG) treatment for urothelial carcinoma (UC) within previous 1 year. 2. History of HG bladder cancer (papillary or carcinoma in situ) in the past 2 years. 3. Known allergy or sensitivity to mitomycin that in the Investigator's opinion cannot be readily managed. 4. Clinically significant urethral stricture that would preclude passage of a urethral catheter. 5. History of:
  • neurogenic bladder.
  • active urinary retention.
  • any other condition that would prohibit normal voiding. 6. Past or current T1 UC, muscle invasive UC (ie, T2, T3, T4), metastatic UC, or concurrent upper tract urothelial carcinoma (UTUC). 7. Has an underlying substance abuse or psychiatric disorder such that, in the opinion of the Investigator, the patient would be unable to comply with the protocol. 8. History of prior treatment with an intravesical chemotherapeutic agent in the past 2 years except for a single dose of chemotherapy immediately after any previous transurethral resection of bladder tumors (TURBT). 9. Has participated in a study with an investigational agent or device within 30 days of enrollment.

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Sacituzumab Govitecan Plus Enfortumab Vedotin for Metastatic Urothelial Carcinoma Progressing on Platinum-based Chemotherapy and PD1/L1 Inhibitors: the Double Antibody Drug Conjugate (DAD) Phase I Trial


Condition: Urothelial Cancer, Metastatic Urothelial Carcinoma, Metastatic Urothelial Carcinoma of the Renal Pelvis and Ureter, Bladder Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT04724018

Sponsor: Dana-Farber Cancer Institute

Phase: Phase 1

Eligibility:

  • Age: minimum 18 Years maximum N/A
  • Gender: All

Inclusion Criteria:

  • Participants must have histologically documented confirmed predominant urothelial carcinoma (i.e. of the bladder, renal pelvis, ureter or urethra). Patients with squamous differentiation or mixed cell types are eligible; small-cell carcinoma is not allowed. Patients with locally advanced unresectable disease are eligible.
  • Patient must have received prior treatment with a checkpoint inhibitor (CPI) in locally advanced or metastatic urothelial cancer setting. Patients who received CPI therapy in the neoadjuvant/adjuvant setting and had recurrent or progressive disease either during or within 3 months of therapy completion are eligible. A CPI is defined as a PD-1 or PD-L1 inhibitor.
  • Patients must have received prior treatment with platinum containing therapy defined as within the adjuvant/neoadjuvant setting with recurrent or progressive disease within 12 months or receiving treatment with platinum in locally advanced or metastatic setting.
  • Age ≥18 years. Because no dosing or adverse event data are currently available on the use of EV in combination with SG in participants <18 years of age, children are excluded from this study, but will be eligible for future pediatric trials.
  • ECOG performance status 0-1.
  • Participants must have adequate organ and marrow function as defined below:
  • Leukocytes ≥3,000/mcL
  • Absolute neutrophil count ≥1,500/mcL
  • Platelets ≥100,000/mcL
  • Total bilirubin ≤ institutional upper limit of normal (ULN)
  • AST(SGOT)/ALT(SGPT) ≤2.5x institutional ULN OR ≤5x ULN with liver metastases and serum albumin > 3 g/dL
  • Glomerular filtration rate (GFR) ≥30 mL/min/1.73 m2 (by Cockcroft Gault formula)
  • Human immunodeficiency virus (HIV)-infected participants on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial.
  • For participants with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.
  • Participants with a history of hepatitis C virus (HCV) infection must have been treated and cured. For participants with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load.
  • Participants with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, participants should be class 2B or better.
  • Have measurable disease by computed tomography (CT) or magnetic resonance imaging (MRI) as per response evaluation criteria in solid tumors version 1.1 (RECIST 1.1 criteria). Tumor lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions
  • Female subjects of childbearing potential must have a negative urine or serum pregnancy test within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
  • Female subjects of childbearing potential must be willing to use 2 methods of birth control or be surgically sterile or abstain from heterosexual activity for the course of the study through 6 months after the last dose of study medication. Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for >2 years
  • The effects of SG and EV on the developing human fetus are unknown. Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of SG administration.
  • Ability to understand and the willingness to sign a written informed consent document. Exclusion Criteria: Subjects meeting any of the following

Exclusion Criteria:

  • Subjects meeting any of the following exclusion criteria at Screening/Day 1 of treatment will not be enrolled in the study.
  • Women who are pregnant or lactating. Pregnant women are excluded from this study because SG and EV have potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with EV or SG, breastfeeding should be discontinued if the mother is treated on protocol.
  • Have had a prior anti-cancer biologic agent within 4 weeks prior to Cycle 1 Day 1 (C1D1) or have had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to C1D1. Subjects participating in observational studies are eligible.
  • Presence of any toxicities attributed to prior anti-cancer therapy that are not resolved to Grade 1 or baseline that could impose serious risk for complications before administration of study drug agent
  • Note: If subjects received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
  • Have previously received topoisomerase 1 inhibitors, SG or EV
  • Have an active second malignancy. Subjects with a history of malignancy that have been completely treated, with no evidence of active cancer for 3 years prior to start of therapy on trial (Cycle 1 Day 1 [C1D1]), or subjects with surgically-cured tumors with low risk of recurrence are allowed to enroll.
  • Have known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they have stable CNS disease for at least 4 weeks prior to the first dose of study drug and all neurologic symptoms have returned to baseline, have no evidence of new or enlarging brain metastases, and are taking ≤20 mg/day of prednisone or its equivalent. All subjects with carcinomatous meningitis are excluded regardless of clinical stability.
  • Have active cardiac disease, defined as:
  • Myocardial infarction or unstable angina pectoris within 6 months prior to C1D1
  • History of serious ventricular arrhythmia (i.e., ventricular tachycardia or ventricular fibrillation), high-grade atrioventricular block, or other cardiac arrhythmias requiring anti-arrhythmic medications (except for atrial fibrillation that is well controlled with antiarrhythmic medication); history of QT interval prolongation
  • New York Heart Association (NYHA) Class III or greater congestive heart failure or left ventricular ejection fraction of < 40%
  • Have active chronic inflammatory bowel disease (ulcerative colitis, Crohn's disease) or gastrointestinal (GI) perforation within 6 months of C1D1
  • Have active serious infection requiring antibiotics (Contact medical monitor for clarification)
  • Have other concurrent medical or psychiatric conditions that, in the Investigator's opinion, may be likely to confound study interpretation or prevent completion of study procedures and follow-up examinations.
  • High dose systemic corticosteroids (≥20 mg of prednisone or its equivalent) are not allowed within 2 weeks prior to C1D1.
  • Participants who are receiving any other investigational agents.
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to EV or SG or any excipient contained in the drug formulations (including 2-(N-morpholino) ethane sulfonic acid (MES), histidine, treahalose dihydrate polysorbate 80 and polysorbate 20).
  • Participants with uncontrolled intercurrent illness.
  • Participants with psychiatric illness/social situations that would limit compliance with study requirements.
  • Patients with uncontrolled diabetes. Uncontrolled diabetes is defined as hemoglobin A1C >8% or 7-8% with associated diabetes symptoms that are otherwise not explained
  • Uncontrolled tumor related bone pain or impending spinal cord compression.

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A Phase 3, Randomized, Open-label Study to Evaluate Perioperative Enfortumab Vedotin Plus Pembrolizumab (MK-3475) Versus Neoadjuvant Gemcitabine and Cisplatin in Cisplatin-eligible Participants With Muscle-invasive Bladder Cancer (KEYNOTE-B15 / EV-304)


Condition: Muscle Invasive Bladder Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT04700124

Sponsor: Merck Sharp & Dohme LLC

Phase: Phase 3

Eligibility:

  • Age: minimum 18 Years maximum N/A
  • Gender: All

Inclusion Criteria:

  • Have a histologically confirmed diagnosis of urothelial carcinoma (UC) / muscle invasive bladder cancer (MIBC) (T2-T4aN0M0 or T1-T4aN1M0) with predominant (≥50%) urothelial histology
  • Have clinically non-metastatic bladder cancer (N≤1 M0) determined by imaging (computed tomography (CT) or magnetic resonance imaging (MRI) of the chest/abdomen/pelvis
  • Be deemed eligible for Radical Cystectomy (RC) + Pelvic Lymph Node Dissection (PLND)
  • Have Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  • Have adequate organ function

Exclusion Criteria:

  • Has a known additional malignancy that is progressing or has required active anti-cancer treatment ≤3 years of study randomization with certain exceptions
  • Has received any prior systemic treatment for MIBC or non-invasive muscle bladder cancer (NMIBC
  • prior treatment for NMIBC with intravesical BCG/chemotherapy is permitted) or prior therapy with an anti- programmed cell death 1 (PD-1), anti-programmed cell death ligand 1/ ligand 2 (PD-L1/L2), or anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4)
  • Has ≥N2 disease or metastatic disease (M1) as identified by imaging
  • Is cisplatin-ineligible, as defined by meeting any one of the cisplatin ineligibility criteria as per protocol
  • Has received prior systemic anticancer therapy including investigational agents within 3 years of randomization or any radiotherapy to the bladder
  • Has undergone partial cystectomy of the bladder to remove any NMIBC or MIBC
  • Has received a live or live attenuated vaccine within 30 days before the first dose of study intervention
  • Has a diagnosis of immunodeficiency or has a known history of human immunodeficiency virus (HIV) infection. Hepatitis B infection or known active Hepatitis C infection
  • Has a known psychiatric or substance abuse disorder
  • Has had an allogenic tissue/solid organ transplant
  • Has ongoing sensory or motor neuropathy Grade 2 or higher
  • Has active keratitis (superficial punctate keratitis) or corneal ulcerations
  • Has a history of uncontrolled diabetes defined as hemoglobin A1c (HbA1c) ≥8% or HbA1c 7% to <8% with associated diabetes symptoms

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Phase II Trial of Intravesical Gemcitabine and MK-3475 (Pembrolizumab) in the Treatment of Patients With BCG-Unresponsive Non-Muscle Invasive Bladder Cancer


Condition: Bladder Urothelial Carcinoma In Situ, Infiltrating Bladder Mixed Carcinoma, Stage 0a Bladder Cancer AJCC v8, Stage 0is Bladder Cancer AJCC v8, Stage I Bladder Cancer AJCC v8

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT04164082

Sponsor: National Cancer Institute (NCI)

Phase: Phase 2

Eligibility:

  • Age: minimum 18 Years maximum N/A
  • Gender: All

Inclusion Criteria:

  • High grade Ta, T1 or CIS urothelial carcinoma. Accrual of patients with Ta or T1 disease may be closed to ensure adequate patients enrollment to meet the primary endpoint
  • Persistent disease (defined as not achieving disease free status) after completing therapy with at least induction BCG (>= 5 doses) and the first round of maintenance or second induction course (>= 2 doses). The subsequent round of BCG, either maintenance or repeat induction, must be given within 6 months of initial induction BCG.
  • Persistent high risk NMIBC (T1, high grade Ta and/or CIS) must be within 9 months of the last BCG instillation despite having received adequate BCG as defined above.
  • Registration must be within 12 months of last BCG instillation
  • High grade T1 after completing therapy with at least induction BCG (>= 5 doses) or after completing therapy with at least induction BCG (>= 5 doses) and first round of maintenance or second induction course (>= 2 doses). The subsequent round of BCG, either maintenance or repeat induction, must be given within 6 months of initial induction BCG
  • Persistent high risk NMIBC (T1, high grade Ta and/or CIS) must be within 9 months of the last BCG instillation despite having received adequate BCG as defined above.
  • Registration must be within 12 months of last BCG instillation
  • Patients who are disease free at 6 months after starting BCG but have high grade recurrence (T1, Ta, CIS) while on maintenance therapy would be eligible
  • The recurrence must be within 6 months of the last BCG dose.
  • Registration must be within 12 months of last maintenance BCG instillation
  • Patients must be deemed unfit for radical cystectomy by the treating physician or refuse radical cystectomy
  • All patients must have histologically confirmed urothelial cancer of the bladder within 60 days prior to registration
  • All visible tumor must be completely resected 60 days prior to registration (residual pure CIS is permitted)
  • All patients must have had a cystoscopy (or transurethral resection of bladder tumor [TURBT] with complete resection) without papillary tumor and negative urinary cytology within 28 days of registration. (positive cytology is allowed in patients with CIS)
  • All patients with T1 tumors must undergo a re-staging TURBT within 60 days of registration. There must be uninvolved muscularis propria present in the re-staging TURBT. The initial TURBT prior to re-staging TURBT may be greater than 60 days prior to registration
  • Patients must have had imaging with computed tomography (CT) or magnetic resonance imaging (MRI) abdomen/pelvis within 90 days of registration demonstrating no evidence of metastasis.
  • Not pregnant and not nursing, because this study involves an agent that has known genotoxic, mutagenic and teratogenic effects
  • Women and men of reproductive potential should agree to use an appropriate method of birth control throughout their participation in this study due to the teratogenic potential of the therapy utilized in this trial. Include as applicable: Appropriate methods of birth control include abstinence, oral contraceptives, implantable hormonal contraceptives or double barrier method (diaphragm plus condom)
  • A woman of childbearing potential (WOCBP) must not have a positive urine pregnancy test within 7 days prior to registration. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
  • Patients must not be pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with registration through the last dose of treatment
  • Age >= 18 years
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-2
  • Absolute neutrophil count (ANC) >= 1,500/mm^3
  • Platelet count >= 100,000/mm^3
  • Hemoglobin >= 9.0 g/dL
  • Creatinine =< 1.5 x upper limit of normal (ULN)
  • In patients with creatinine > 1.5 x ULN, if measured or calculated creatinine clearance > 30 mL/min, then patient is eligible
  • Total bilirubin =< 1.5 x ULN
  • In patients with a total bilirubin > 1.5 x ULN, if direct bilirubin < 1.0 X ULN, then patient is eligible
  • Aspartate aminotransferase (AST)/ alanine aminotransferase (ALT) =< 2.5 x ULN
  • Patients with human immunodeficiency virus (HIV) are eligible with the following:
  • On effective anti-retroviral therapy with undetectable viral load within 6 months of registration

Exclusion Criteria:

  • Mixed variant histology (adenocarcinoma, squamous cell carcinoma) is eligible, but pure variant histology is ineligible.
  • Patients cannot have had a history of urothelial carcinoma in the ureters or prostatic urethra 24 months prior to registration
  • Patients must not be currently participating in or have participated in a study of an investigational agent or have used an investigational device within 4 weeks prior to study registration
  • Note: Participants who have entered the follow-up phase of an investigational study may participate as long as it has been more than 4 weeks after the last dose of the previous investigational agent at time of registration
  • Patients must not have prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g., CTLA-4, OX 40, CD137)
  • Patients must not have undergone prior allogeneic hematopoietic stem cell transplantation within the last 5 years prior to registration. (Participants who have had a transplant greater than 5 years ago are eligible as long as there are no symptoms of graft versus host disease [GVHD])
  • Patients must not have received prior systemic anti-cancer therapy including investigational agents within 4 weeks prior to treatment
  • Note: Participants must have recovered from all adverse events (AEs) due to previous therapies to =< grade 1 or baseline. Participants with =< grade 2 neuropathy may be eligible
  • Note: If participant received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting study treatment
  • Patients must not have received prior radiotherapy within 2 weeks of study registration. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis
  • Patients must not have received radiation therapy to the lung that is > 30 Gy within 6 months prior to trial registration
  • Patients must not have had an active autoimmune disease requiring systemic treatment within 7 days prior to registration. Autoimmune diseases include, but not limited to, lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid syndrome, Wegener's granulomatosis, Sjogren's syndrome, Bell's palsy, Guillain-Barre syndrome, multiple sclerosis, autoimmune thyroid disease, vasculitis, or glomerulonephritis
  • Patients must not have a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to registration
  • Note: Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed
  • Patients must not have a known psychiatric or substance abuse disorder that would interfere with the participant's ability to cooperate with the requirements of the study
  • Patients must not have active tuberculosis
  • Patients must not have been treated with antibiotics for an active infection within 14 days prior to registration. Prophylactic antibiotics are permitted. Treatment for a urinary tract infection (UTI) is allowed but must be deemed adequately treated by the treating physician prior the start of cycle 1 (C1) day 1 (D1)
  • Patients must not have a history of idiopathic pulmonary fibrosis or organizing pneumonia
  • Patients must not have a history of (non-infectious) pneumonitis that required steroids or have current pneumonitis
  • HIV-infected participants must not have a history of Kaposi sarcoma and/or multicentric Castleman disease
  • Patients must not have a known additional malignancy that has had progression or has required active treatment in the last three years. Exceptions include basal or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer. A history of prostate cancer that was treated with definitive intent is allowed, provided that the prostate-specific antigen (PSA) is undetectable for at least 1 year while off androgen deprivation therapy
  • Patients must not have known active CNS metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, i.e., without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study treatment
  • Patients must not have severe hypersensitivity (>= grade 3) to pembrolizumab and/or any of its excipients
  • Patients must not have an active infection requiring systemic therapy
  • Patients must not have a known history of hepatitis B (defined as hepatitis B surface antigen [HBsAg] reactive) or known active hepatitis C virus (defined as hepatitis C virus [HCV] ribonucleic acid [RNA] [qualitative] is detected) infection
  • Note: No testing for hepatitis B and hepatitis C is required unless mandated by a local health authority
  • Patients must not have received live vaccines within 30 days of study drug administration. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guerin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g., FluMist) are live attenuated vaccines and are not allowed. COVID-19 vaccinations are permitted.
  • Physicians should consider whether any of the following may render the patient inappropriate for this protocol:
  • Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not in the best interest of the participant to participate, in the opinion of the treating investigator

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Multicenter Phase 3 Pivotal Study to Evaluate the Safety and Efficacy of TOOKAD (Padeliporfin) Vascular Targeted Photodynamic Therapy in the Treatment of Low Grade Upper Tract Urothelial Cancer


Condition: Transitional Cell Cancer of Renal Pelvis and Ureter

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT04620239

Sponsor: Steba Biotech S.A.

Phase: Phase 3

Eligibility:

  • Age: minimum 18 Years maximum N/A
  • Gender: All

Inclusion Criteria:

  • Male and female patients 18 years or older
  • Able to understand and provide written informed consent and willing to comply with all tests and procedures associated with the study
  • New or recurrent low-grade, non-invasive UTUC disease
  • Biopsy-proven disease . A concurrence of the central pathology reader will be required for eligibility.
  • Up to 2 biopsy-proven sites of low-grade involvement with the largest tumor (index tumor) between 5 mm and 15 mm in diameter (as measured by endoscopy), both located in the calyces,renal pelvis or in the ureter of the ipsilateral kidney, with an absence of high-grade cells on cytology. (Ureter involvement should be in one anatomical location with no more than 20 mm of contiguous ureteral length)
  • Karnofsky Performance Status ≥ 50%
  • Adequate organ function defined at baseline as:
  • ANC ≥1,000/ μl,
  • Platelets ≥75,000/ μl, Hb ≥9 g/dl,
  • INR ≤ 2
  • Estimated glomerular giltration rate (eGFR) ≥30 ml/min (using CKD-EPI Method)
  • Total serum bilirubin <3 mg/dL, AST/ALT ≤5× upper limit of normal

Exclusion Criteria:

  • Current high-grade or muscle invasive (>pT1) urothelial carcinoma of the bladder
  • Carcinoma in situ (CIS) current or previous in the upper urinary tract
  • History of invasive T2 or higher urothelial cancer in past 2 years
  • Participation in another clinical study involving an investigational product within 1 month before study entry
  • BCG or local chemotherapy treatment (including VEGF-targeted therapy) in the upper urinary tract within 2 months prior to inclusion
  • Systemic chemotherapy treatment (including VEGF-targeted therapy) within 2 months prior to enrollment
  • Prohibited medication that could not be adjusted or discontinued prior to study treatment • Patients with photosensitive skin diseases or porphyria
  • Any other medical or psychiatric co-morbidities, including decompensated heart failure, unstable angina or coronary artery disease or severe pulmonary or liver disease or current heavy smoker that, in the opinion of the study investigator, would make the patient a poor candidate for the study
  • Pregnant or breast-feeding women.Women of childbearing potential (WOCBP) must undergo a negative serum pregnancy test prior to study entry.
  • Men and women of reproductive potential not willing to observe conventional and effective birth control for the duration of treatment and for 90 days following the last padeliporfin VTP treatment.

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A Phase 2 Basket Study of Tucatinib in Combination With Trastuzumab in Subjects With Previously Treated, Locally Advanced Unresectable or Metastatic Solid Tumors Driven by HER2 Alterations


Condition: Uterine Neoplasms, Uterine Cervical Neoplasms, Biliary Tract Neoplasms, Urologic Neoplasms, Carcinoma, Non-Small-Cell Lung, HER2 Mutations Breast Neoplasms

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT04579380

Sponsor: Seagen Inc.

Phase: Phase 2

Eligibility:

  • Age: minimum 18 Years maximum N/A
  • Gender: All

Inclusion Criteria:

  • Histologically or cytologically confirmed diagnosis of locally-advanced unresectable or metastatic solid tumor, including primary brain tumors
  • Participants with non-squamous NSCLC must have progressed during or after standard treatment or for which no standard treatment is available
  • Participants with other disease types must have progressed during or after ≥1 prior line of systemic therapy for locally-advanced unresectable or metastatic disease
  • Disease progression during or after, or intolerance of, the most recent line of systemic therapy
  • Disease demonstrating HER2 alterations (overexpression/amplification or HER2 activating mutations), as determined by local or central testing processed in a Clinical Laboratory Improvement Amendments (CLIA)- or International Organization for Standardization (ISO) accredited laboratory, according to one of the following:
  • HER2 overexpression/amplification from fresh or archival tumor tissue or blood
  • Known activating HER2 mutations detected in fresh or archival tumor tissue or blood
  • Have measurable disease per RECIST v1.1 criteria according to investigator assessment
  • Have Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 Exclusion Criteria
  • Participants with breast cancer, gastric or gastroesophageal junction adenocarcinoma, or CRC whose disease shows HER2 amplification/overexpression.
  • Previous treatment with HER2-directed therapy; participants with uterine serous carcinoma or HER2-mutated gastric or gastroesophageal junction adenocarcinoma without HER2-overexpression/amplification may have received prior trastuzumab
  • Known hypersensitivity to any component of the drug formulation of tucatinib or trastuzumab (drug substance, excipients, murine proteins), or any component of the drug formulation of fulvestrant in participants with HR+ HER2-mutated breast cancer
  • History of exposure to a 360 mg/m² doxorubicin-equivalent or >720 mg/m^2 epirubicin-equivalent cumulative dose of anthracyclines
  • Treatment with any systemic anti-cancer therapy, radiation therapy, major surgery, or experimental agent within ≤3 weeks of first dose of study treatment or are currently participating in another interventional clinical trial. There are additional inclusion and

Exclusion Criteria:

  • Participants with breast cancer, gastric or gastroesophageal junction adenocarcinoma, or CRC whose disease shows HER2 amplification/overexpression.
  • Previous treatment with HER2-directed therapy; participants with uterine serous carcinoma or HER2-mutated gastric or gastroesophageal junction adenocarcinoma without HER2-overexpression/amplification may have received prior trastuzumab
  • Known hypersensitivity to any component of the drug formulation of tucatinib or trastuzumab (drug substance, excipients, murine proteins), or any component of the drug formulation of fulvestrant in participants with HR+ HER2-mutated breast cancer
  • History of exposure to a 360 mg/m² doxorubicin-equivalent or >720 mg/m^2 epirubicin-equivalent cumulative dose of anthracyclines
  • Treatment with any systemic anti-cancer therapy, radiation therapy, major surgery, or experimental agent within ≤3 weeks of first dose of study treatment or are currently participating in another interventional clinical trial. There are additional inclusion and exclusion criteria. The study center will determine if criteria for participation are met.

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Treatment Of Metastatic Bladder Cancer at the Time Of Biochemical reLApse Following Radical Cystectomy


Condition: Bladder Cancer, Bladder Cancer, Metastatic

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT04138628

Sponsor: Jørgen Bjerggaard Jensen

Phase: Phase 2

Eligibility:

  • Age: minimum 18 Years maximum N/A
  • Gender: All

Inclusion Criteria:

  • ≥18 years of age at the time of signing the Informed Consent Form
  • For male study subjects: agreement to remain abstinent (refrain from heterosexual intercourse) or use a condom, and agreement to refrain from donating sperm.
  • Signed Informed Consent Form
  • ECOG PS 0, 1 or 2
  • Is, according to the Investigator's judgement, able to comply with the trial protocol
  • Ability to understand the Participant Information Sheet orally and in writing
  • Preoperative PET/CT of thorax, abdomen, and pelvis with no suspicion of organ metastases or lymph node metastasis* above the aortic bifuraction
  • Study Subjects undergoing radical cystectomy due to histologically documented muscle invasive urothelial carcinoma (including subtypes) stage cT2-4a in the urinary bladder following NAC** in cisplatin-fit Study Subjects.
  • Study Subjects who have undergone down-staging chemotherapy because of lymph node metastasis with no organ metastases can be included if complete response regarding lymph nodes are identified on preoperative imaging.
  • NAC includes Study Subjects who have stopped after one course of chemotherapy because of side effects or local non-metastatic progression

Exclusion Criteria:

  • Subjects undergoing non-radical cystectomy for palliative reasons
  • Non-radical surgery estimated intraoperative
  • Other histology of BC than urothelial carcinoma
  • mixed tumours with urothelial features are allowed
  • Concomitant invasive cancer within 5 years other than non-melanoma skin cancer and prostate cancer without metastasis
  • Known contraindication to immunotherapy
  • A history of autoimmune disease. Study Subjects with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll. Subjects with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
  • Study Subjects who meet any of the following criteria will be excluded from study entry:
  • History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan
  • Treatment with systemic immunostimulatory agents (including, but not limited to, interferon and interleukin 2 [IL-2]) within 4 weeks or 5 drug elimination half-lives (whichever is longer) prior to initiation of study treatment
  • HIV positive
  • History of pneumonitis (History of radiation pneumonitis in the radiation field (fibrosis) is permitted.
  • Hepatitis B or hepatitis C infection
  • Subjects who have received a live, attenuated vaccine within 28 days prior to enrolment

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An Open-label, Randomized, Controlled Phase 3 Study of Enfortumab Vedotin in Combination With Pembrolizumab Versus Chemotherapy Alone in Previously Untreated Locally Advanced or Metastatic Urothelial Cancer


Condition: Urothelial Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT04223856

Sponsor: Astellas Pharma Global Development, Inc.

Phase: Phase 3

Eligibility:

  • Age: minimum 18 Years maximum N/A
  • Gender: All

Inclusion Criteria:

  • Histologically documented, unresectable locally advanced or metastatic urothelial carcinoma
  • Measurable disease by investigator assessment according to RECIST v1.1
  • Participants with prior definitive radiation therapy must have measurable disease per RECIST v1.1 that is outside the radiation field or has demonstrated unequivocal progression since completion of radiation therapy
  • Participants must not have received prior systemic therapy for locally advanced or metastatic urothelial carcinoma with the following exceptions:
  • Participants that received neoadjuvant chemotherapy with recurrence >12 months from completion of therapy are permitted
  • Participants that received adjuvant chemotherapy following cystectomy with recurrence >12 months from completion of therapy are permitted
  • Must be considered eligible to receive cisplatin- or carboplatin-containing chemotherapy, in the investigator's judgment
  • Archival tumor tissue comprising muscle-invasive urothelial carcinoma or a biopsy of metastatic urothelial carcinoma must be provided for PD-L1 testing prior to randomization
  • Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0, 1, or 2
  • Adequate hematologic and organ function

Exclusion Criteria:

  • Previously received enfortumab vedotin or other monomethyl auristatin E (MMAE)-based antibody-drug conjugate (ADCs)
  • Received prior treatment with a programmed cell death ligand-1 (PD-(L)-1) inhibitor for any malignancy, including earlier stage urothelial cancer (UC), defined as a PD-1 inhibitor or PD-L1 inhibitor
  • Received prior treatment with an agent directed to another stimulatory or co inhibitory T-cell receptor
  • Received anti-cancer treatment with chemotherapy, biologics, or investigational agents not otherwise prohibited by exclusion criterion 1-3 that is not completed 4 weeks prior to first dose of study treatment
  • Uncontrolled diabetes
  • Estimated life expectancy of less than 12 weeks
  • Active central nervous system (CNS) metastases
  • Ongoing clinically significant toxicity associated with prior treatment that has not resolved to ≤ Grade 1 or returned to baseline
  • Currently receiving systemic antimicrobial treatment for active infection (viral, bacterial, or fungal) at the time of randomization. Routine antimicrobial prophylaxis is permitted.
  • Known active hepatitis B, active hepatitis C, or human immunodeficiency virus (HIV) infection.
  • History of another invasive malignancy within 3 years before the first dose of study drug, or any evidence of residual disease from a previously diagnosed malignancy
  • Documented history of a cerebral vascular event (stroke or transient ischemic attack), unstable angina, myocardial infarction, or cardiac symptoms consistent with New York Heart Association (NYHA) Class IV within 6 months prior to randomization
  • Receipt of radiotherapy within 2 weeks prior to randomization
  • Received major surgery (defined as requiring general anesthesia and >24 hour inpatient hospitalization) within 4 weeks prior to randomization
  • Known severe (≥ Grade 3) hypersensitivity to any enfortumab vedotin excipient contained in the drug formulation of enfortumab vedotin
  • Active keratitis or corneal ulcerations
  • History of autoimmune disease that has required systemic treatment in the past 2 years
  • History of idiopathic pulmonary fibrosis, organizing pneumonia, drug induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan
  • Prior allogeneic stem cell or solid organ transplant
  • Received a live attenuated vaccine within 30 days prior to randomization

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A Randomized Open-Label Phase III Study of Sacituzumab Govitecan Versus Treatment of Physician's Choice in Subjects With Metastatic or Locally Advanced Unresectable Urothelial Cancer


Condition: Locally Advanced or Metastatic Unresectable Urothelial Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT04527991

Sponsor: Gilead Sciences

Phase: Phase 3

Eligibility:

  • Age: minimum 18 Years maximum N/A
  • Gender: All

Key Inclusion Criteria:

  • 1. Individuals with histologically documented metastatic or locally advanced unresectable UC defined as
  • Tumor (T) 4b, any node (N) or
  • Any T, N 2-3 Tumors of upper and lower urinary tract are permitted. Mixed histologic types are allowed if urothelial is the predominant histology. 2. Eastern Cooperative Oncology Group (ECOG) performance status (PS) score of 0 or 1. 3. Individuals with progression or recurrence following receipt of platinum-containing regimen and anti programmed cell death protein 1/programmed death-ligand 1 (PD-1/PD-L1) therapy for metastatic or locally advanced unresectable disease will be enrolled.
  • a. Individuals with recurrence or progression ≤12 months following completion of cisplatin-containing chemotherapy given in the neo-adjuvant/adjuvant setting may utilize that line of therapy to be eligible for the study. The 12-month period is counted from completion of surgical intervention or platinum therapy, respectively. These individuals must receive anti PD-1/PD-L1 therapy in the metastatic or locally advanced unresectable setting to be eligible.
  • b. Individuals who received either carboplatin or anti PD-1/PD-L1 therapy in the neo- adjuvant/adjuvant setting will not be able to count that line of therapy towards eligibility for the study.
  • c. Cisplatin ineligible individuals who meet one of the below criteria and who were treated with carboplatin in the metastatic or locally advanced unresectable settings may count that line of therapy towards eligibility. They must then have received anti PD-1/PD-L1 therapy in metastatic or locally advanced unresectable setting to be eligible for the study.
  • Cisplatin ineligibility is defined as meeting one of the following criteria:
  • 1. Creatinine Clearance < 60 mL/min
  • 2. Grade ≥ 2 Audiometric Hearing Loss
  • 3. Grade ≥ 2 Peripheral Neuropathy
  • 4. New York Heart Association (NYHA) Class III heart failure
  • 5. ECOG PS ≥ 2
  • d. Anti PD-1/PD-L1 therapy administered as part of maintenance therapy may be counted towards eligibility for the study
  • e. Individuals who have progressed after receiving enfortumab vedotin in prior lines of therapy, and individuals who are either ineligible or unable to tolerate enfortumab vedotin therapy, are eligible to enroll in the study
  • f. Individuals who received only concurrent chemoradiation for bladder preservation without further systemic therapy are not eligible to enroll in the study. The substitution of carboplatin for cisplatin does not constitute a new regimen provided no new chemotherapeutic agents were added to the regimen and no progression was noted prior to the change in platinum. 4. Individuals with previously treated brain metastases may participate in the study provided they have stable CNS disease for at least 4 weeks prior to the first dose of study drug and stabilization of all neurologic symptoms, have no evidence of new or enlarging brain metastases, and are not using steroids >20 mg of prednisone (or equivalent) daily for brain metastases for at least 7 days prior to first dose of the study drug. 5. Adequate hematologic counts without transfusion or growth factor support within 2 weeks of study drug initiation (hemoglobin ≥ 9 g/dL, absolute neutrophil count (ANC) ≥1,500/mm^3, and platelets ≥100,000/µL). 6. Adequate hepatic function (bilirubin ≤1.5x institutional upper limit of normal (IULN), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x IULN or ≤ 5 x IULN if known liver metastases and serum albumin >3 g/dL). Docetaxel will only be option in TPC arm for Individuals with a total bilirubin ≤1 x IULN, and an AST and/or ALT ≤1.5x IULN if alkaline phosphatase is also >2.5 x IULN. 7. Creatinine clearance ≥30 mL/min as assessed by the Cockcroft-Gault equation or other validated instruments (e.g. Modification of Diet in Renal Disease (MDRD) equation). 8. Females of childbearing potential must have a negative urine or serum pregnancy test within 72 hours prior to receiving the first dose of study drug. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. 9. Females of childbearing potential must be willing to use 2 methods of birth control or be surgically sterile or abstain from heterosexual activity for the course of the study through 6 months after the last dose of study drug. Individuals of childbearing potential are those who have not been surgically sterilized or have not been free from menses for >2 years. 10. Males must agree to use an adequate method of contraception starting with the first dose of study therapy through 6 months after the last dose of study therapy.

Key Exclusion Criteria:

  • 1. Females who are pregnant or lactating. 2. Have had a prior anti-cancer monoclonal antibody (mAb)/ antibody-drug conjugate (ADC) within 4 weeks prior to Cycle 1 Day 1 (C1D1) or have had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to C1D1. Individuals participating in observational studies are eligible. 3. Have received prior chemotherapy for UC with any available SOC therapies in the control arm (i.e., both prior paclitaxel and docetaxel in regions where vinflunine is not an approved therapy, or prior paclitaxel, docetaxel and vinflunine in regions where vinflunine is approved and is commercially available). 4. Have not recovered (i.e., ≤ Grade 1) from AEs due to previously administered chemotherapeutic agent.
  • Note: Individuals with ≤ Grade 2 neuropathy or any grade of alopecia are an exception to this criterion and will qualify for the study.
  • Note: If Individuals received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting study therapy. 5. Have previously received topoisomerase 1 inhibitors. 6. Have an active second malignancy. • Note: Individuals with a history of malignancy that have been completely treated and with no evidence of active cancer for 3 years prior to enrollment, or individuals with surgically cured tumors with low risk of recurrence are allowed to enroll in the study after discussion with the medical monitor. 7. Have active cardiac disease, defined as:
  • Myocardial infarction or unstable angina pectoris within 6 months of C1D1.
  • History of serious ventricular arrhythmia (i.e., ventricular tachycardia or ventricular fibrillation), high-grade atrioventricular block, or other cardiac arrhythmias requiring anti-arrhythmic medications (except for atrial fibrillation that is well controlled with antiarrhythmic medication); history of QT interval prolongation.
  • NYHA Class III or greater congestive heart failure or left ventricular ejection fraction of <40%. 8. Have active chronic inflammatory bowel disease (ulcerative colitis, Crohn's disease) or gastrointestinal (GI) perforation within 6 months of enrollment. 9. Have an active serious infection requiring anti-infective therapy (Contact medical monitor for clarification). 10. Have known history of Human Immunodeficiency Virus (HIV)-1/2 with undetectable viral load and on medications that may interfere with SN-38 metabolism. 11. Have active Hepatitis B Virus (HBV) or Hepatitis C Virus (HCV). In individuals with a history of HBV or HCV, individuals with a detectable viral load will be excluded. 12. Have other concurrent medical or psychiatric conditions that, in the investigator's opinion, may be likely to confound study interpretation or prevent completion of study procedures and follow-up examinations. 13. Have inability to tolerate or are allergic to any potential TPC agent or sacituzumab govitecan-hziy or unable or unwilling to receive the doses specified in the protocol. 14. Have inability to complete all specified study procedures for any reason. Note: Other protocol defined Inclusion/

Exclusion Criteria:

  1. may apply.

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A Phase 3, Randomized, Double-blind, Placebo-controlled Clinical Trial to Study the Efficacy and Safety of Pembrolizumab (MK-3475) in Combination With Chemoradiotherapy (CRT) Versus CRT Alone in Participants With Muscle-invasive Bladder Cancer (MIBC) (KEYNOTE-992)


Condition: Urinary Bladder Neoplasms

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT04241185

Sponsor: Merck Sharp & Dohme LLC

Phase: Phase 3

Eligibility:

  • Age: minimum 18 Years maximum N/A
  • Gender: All

Inclusion Criteria:

  • Has a histologically confirmed initial diagnosis of muscle-invasive bladder cancer (MIBC) with predominant urothelial histology
  • Has clinically non-metastatic bladder cancer (N0M0)
  • Has planned and is eligible to receive chemoradiotherapy (CRT) and one of the protocol-specified radiosensitizing chemotherapy regimens
  • Has Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
  • Demonstrates adequate organ function
  • Male participants are eligible to participate if they agree to the following during the intervention period and for at least 90 days after the last dose of CRT treatment:
  • Refrain from donating sperm
  • Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent; or must agree to use contraception unless confirmed to be azoospermic
  • A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies:
  • Is not a woman of childbearing potential (WOCBP)
  • Is a WOCBP and using a contraceptive method that is highly effective (with a failure rate of <1% per year), with low user dependency or be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis), during the intervention period and for at least 180 days the time needed to eliminate each study intervention after the last dose of study intervention; and agrees not to donate eggs (ova, oocytes) to others or freeze/store for her own use for the purpose of reproduction during this period. The length of time required to continue contraception for each study intervention is as follows: MK-3475
  • 120 days and CRT
  • 180 days

Exclusion Criteria:

  • Has the presence of diffuse carcinoma in situ (CIS) (multiple foci of CIS) throughout the bladder
  • Has the presence of urothelial carcinoma (UC) at any site outside of the urinary bladder in the previous 2 years except for Ta stage/T1 stage/CIS of the upper tract if the participant has undergone a complete nephroureterectomy
  • Has a known additional malignancy that is progressing or has required active therapy within the past 3 years, except basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial bladder cancer or other carcinoma in situ that has undergone potentially curative therapy
  • Has the presence of bilateral hydronephrosis
  • Has limited bladder function with frequency of small amounts of urine (< 30 mL), urinary incontinence, or requires self-catheterization or a permanent indwelling catheter
  • Has received prior pelvic/local radiation therapy or any antineoplastic treatment for muscle-invasive bladder cancer (MIBC). Treatment for non-muscle invasive bladder cancer (NMIBC) with intravesical instillation therapy that was completed ≥28 days prior to randomization is allowed. Prior systemic treatment of NMIBC is not permitted.
  • Received prior therapy with an anti-PD-1 (programmed cell death protein 1), anti-PD-L1 (programmed death-ligand 1), or anti-PD-L2 (programmed cell death 1 ligand 2), or with an agent directed to another stimulatory or coinhibitory T-cell receptor (e.g., CTLA-4 [cytotoxic T-lymphocyte-associated protein 4], OX 40, or CD137 [cluster of differentiation 137])
  • Has received a live vaccine within 30 days before the first dose of study medication
  • Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks before the first dose of study medication
  • Has known severe hypersensitivity (≥Grade 3) to the selected chemotherapy regimen, and/or any of their excipients and excipients of pembrolizumab
  • Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days before the first dose of study medication
  • Has an active autoimmune disease that has required systemic treatment in the past 2 years (ie, with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed
  • Has a history of non-infectious pneumonitis that required steroids or has current pneumonitis
  • Has an active infection requiring systemic therapy
  • Has a known history of human immunodeficiency virus (HIV) infection
  • Has a known history of Hepatitis B or known active Hepatitis C virus infection
  • Has a known history of active tuberculosis (TB; Bacillus tuberculosis)
  • Has a known psychiatric or substance abuse disorder that would interfere with the participant's ability to cooperate with the requirements of the study
  • Has had an allogenic tissue/solid organ transplant

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Phase 3, Multicenter, Double-Blind, Randomized, Placebo-Controlled Trial of Infigratinib for the Adjuvant Treatment of Subjects With Invasive Urothelial Carcinoma With Susceptible FGFR3 Genetic Alterations (PROOF 302)


Condition: Upper Tract Urothelial Carcinomas, Urothelial Bladder Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT04197986

Sponsor: QED Therapeutics, Inc.

Phase: Phase 3

Eligibility:

  • Age: minimum 18 Years maximum N/A
  • Gender: All

Key Inclusion Criteria:

  • 1. Are randomized within 120 days following nephroureterectomy, distal ureterectomy or cystectomy. 2. Have histologically or cytologically confirmed, invasive urothelial carcinoma with susceptible FGFR3 alterations. Variant histology is allowed provided urothelial carcinoma is predominant (>50%). Neuroendocrine (including small and large cell), sarcomatoid, and plasmacytoid variants are excluded (any component). 1. Regarding samples and documentation of FGFR3
  • i. FGFR3 mutation is confirmed if: FGFR3 gene is mutated in Exon 7 (R248C, S249C), Exon 10 (G370C, A391E, Y373C), or Exon 15 (K650M/T, K650E/Q) OR
  • ii. FGFR3 gene fusion or FGFR3 rearrangement is confirmed based on the following genomic criteria if:
  • Any fusion/rearrangement with a literature-derived known partner gene regardless of strand or frame.
  • Fusion/rearrangements in the same strand that are in frame with a novel partner gene.
  • Fusion/rearrangements with one breakpoint in the intron 17
  • exon 18 hotspot region and the other breakpoint in an intergenic region or another gene. This rule excludes 3' duplications comprising only exon 18.
  • iii. The amino acid numbers for the FGFR3 mutations refer to the functional FGFR3 isoform 1 (NP_000133.1) that is the NCBI Refseq ID used to report genetic alterations in FGFR3 by the FoundationOne® CDx test (F1CDx, Foundation Medicine, USA).
  • iv. FGFR3 alteration must be confirmed by Foundation Medicine for F1CDx testing:
  • The tumor sample to be used should be from the definitive surgical resection (cystectomy, nephroureterectomy, or distal ureterectomy), or from an archival biopsy of confirmed invasive urothelial carcinoma (≥pT2). 2. If status post neoadjuvant chemotherapy, pathologic stage at surgical resection must be Stage ≥ ypT2 and/or yN+. Prior neoadjuvant therapy is defined as at least 3 cycles of neoadjuvant cisplatin-based chemotherapy with a planned cisplatin dose of 70 mg/m2/cycle. Subjects who received less than this or non-cisplatin-based neoadjuvant treatment are not excluded. 3. If not status post neoadjuvant chemotherapy, is ineligible to receive cisplatin-based adjuvant chemotherapy based on Galsky criteria: 4. Subjects who refuse cisplatin-based chemotherapy or who are ineligible to receive cisplatin-based chemotherapy based on Galsky criteria must also meet the following criteria: 5. Must have a centrally reviewed negative postoperative computed tomography (CT) (defined as lymph nodes with short axis <1.0 cm and without growth and no distant metastases according to [RECIST v1.1 criteria or negative biopsy within 28 days before randomization to confirm absence of disease at baseline. 3. Have Eastern Cooperative Oncology Group (ECOG) performance status of ≤2. 4. If a woman of childbearing potential, must have a negative pregnancy test within 7 days of the first dose of study drug. Sexually active males must use a condom during intercourse while taking study drug and for 1 month after the last dose of study drug and should not father a child during this period

Key Exclusion Criteria:

  1. Presence of positive invasive surgical margins following nephroureterectomy, distal ureterectomy, or cystectomy. In subjects not eligible for further surgery, radiotherapy, or other efficacious treatment, microscopic positive noninvasive margins (eg, carcinoma in situ) without gross residual disease are allowed.
  2. Have received Bacillus Calmette-Guerin (BCG) or other intravesical therapy for Non-Muscle Invasive Bladder Cancer (NMIBC) within the previous 30 days.
  3. Are currently receiving or are planning to receive during participation in this study, treatment with agents that are known moderate or strong inducers or inhibitors of CYP3A4 and medications which increase serum phosphorus and/or calcium concentration. Prior anticancer or other therapies are restricted as follows:
  4. Prior adjuvant treatment for urothelial cancer is not allowed.
  5. Prior neoadjuvant therapy (eg, chemotherapy, immunotherapy, or investigational) is allowed if inclusion criterion #4 is met. Prior neoadjuvant chemotherapy must have been completed within a period of time that is greater than the cycle length used for that treatment before first dose of study drug.
  6. Prior biologic, immunotherapy, or investigational therapy should have been completed within a period that is ≥5 half-lives or 30 days, whichever is shorter, before the first dose of study drug.
  7. Have previously or currently is receiving treatment with a mitogen-activated protein kinase (MEK) or selective FGFR inhibitor.
  8. Have a history of primary malignancy within the past 3 years other than (1) invasive UBC or UTUC (ie, disease under study), (2) noninvasive urothelial carcinoma, (3) any adequately treated in situ carcinoma or non-melanoma carcinoma of the skin, (4) any other curatively treated malignancy that is not expected to require treatment for recurrence during participation in the study, or (5) an untreated cancer on active surveillance that may not affect the subject's survival status for ≥3 years based on clinician assessment/statement and with medical monitor approval.
  9. Have current evidence of corneal keratopathy or retinal disorder confirmed by ophthalmic examination. Subjects with asymptomatic ophthalmic conditions assessed by the investigator to pose minimal risk for study participation may be enrolled in the study.
  10. Have a history and/or current evidence of extensive tissue calcification
  11. Have impaired gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral infigratinib
  12. Have current evidence of endocrine alterations of calcium/phosphate homeostasis (eg, parathyroid disorders, history of parathyroidectomy, tumor lysis, tumoral calcinosis), unless well controlled.
  13. Have consumed grapefruit, grapefruit juice, grapefruit hybrids, pomegranates, star fruits, pomelos, or Seville oranges or products containing juice of these fruits within 7 days before the first dose of study drug; have taken any Chinese herbal medicine or Chinese patent medicine treatments with anticancer activity within 14 days of the first dose of study drug.
  14. Have insufficient bone marrow function:
  15. Absolute neutrophil count (ANC) <1,000/mm3 (1.0 × 109/L).
  16. Platelets <75,000/mm3 (<75 × 109/L).
  17. Hemoglobin <8.5 g/dL; transfusion support is allowed if >1 week before randomization and hemoglobin remains stable.
  18. Have insufficient hepatic and renal function:
  19. Total bilirubin >1.5 × upper limit of normal (ULN) of the testing laboratory (for subjects with documented Gilbert syndrome, direct bilirubin must be ≤1.5 × ULN and enrollment requires approval by the medical monitor).
  20. AST/SGOT and ALT/SGPT >2.5 × ULN of the testing laboratory.
  21. Serum creatinine >1.5 × ULN or a calculated or measured creatinine clearance of <30 mL/min.
  22. Have amylase or lipase >2.0 × ULN.
  23. Have abnormal calcium or phosphorus:
  24. Inorganic phosphorus higher than 1.02 × ULN of the testing laboratory.
  25. Total serum calcium (can be corrected) higher than 1.02 × ULN of the testing laboratory.
  26. Have clinically significant cardiac disease including any of the following:
  27. New York Heart Association (NYHA) Class ≥2B; subjects with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the NYHA classification.
  28. Uncontrolled hypertension
  29. Presence of CTCAE v5.0 Grade ≥2 ventricular arrhythmias, atrial fibrillation, bradycardia, or conduction abnormality.
  30. Unstable angina pectoris or acute myocardial infarction ≤3 months before the first dose of study drug.
  31. Average QTcF >470 msec (males and females). Note: If the QTcF is >470 msec in the first ECG, a total of 3 ECGs separated by ≥5 minutes should be performed. If the average of these 3 consecutive results for QTcF is ≤470 msec, the subject meets eligibility in this regard.
  32. History of congenital long QT syndrome.
  33. Have had a recent (≤3 months before the first dose of study drug) transient ischemic attack or stroke.
  34. If female, are pregnant or nursing (lactating).

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Cabozantinib Plus Pembrolizumab as First-Line Therapy for Cisplatin-Ineligible Advanced Urothelial Carcinoma (PemCab)


Condition: Metastatic Urothelial Carcinoma, Bladder Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03534804

Sponsor: University of Utah

Phase: Phase 2

Eligibility:

  • Age: minimum 18 Years maximum N/A
  • Gender: All

Inclusion Criteria:

  • Histologically proven transitional cell or urothelial carcinoma.
  • The following qualifications for patients with locally advanced or metastatic urothelial carcinoma:
  • Patients who are not eligible for cisplatin-containing chemotherapy AND whose tumors express PD-L1 (Combined Positive Score (CPS) ≥ 10 as determined by an FDA-approved test;
  • Patients who are not eligible for any platinum-containing chemotherapy regardless of PD-L1 status.
  • Metastatic (any N+ or M1) or locally advanced, unresectable (T4bN0) disease.
  • Measurable disease is required as determined by RECIST v1.1.
  • Performance Status ECOG 0-2
  • Cisplatin-ineligibility based on ≥1 of the following:
  • Estimated creatinine clearance between ≥30 and <60 ml/min (Cockcroft-Gault formula)
  • ECOG PS>1
  • Hearing loss
  • Baseline neuropathy > grade 1.
  • Patient refusal
  • Be greater to or equal to 18 years of age on day of signing informed consent.
  • Serum albumin ≥ 2.8 g/dl
  • Alkaline phosphatase (ALP) ≤ 3 × upper limit of normal (ULN). ALP ≤ 5 × ULN with documented bone metastases.
  • Negative serum or urine pregnancy test at screening for women of childbearing potential.
  • Highly effective contraception for both male and female subjects throughout the study and for at least 120 days after last pembrolizumab treatment administration if the risk of conception exists.
  • Must have recovered from adverse effects of any prior surgery, radiotherapy or other antineoplastic therapy to grade ≤ 2. If notrecovered to grade ≤ 2, these must be deemed to be irreversible adverse events related to prior surgery and/or radiation therapy (such as incontinence or sexual dysfunction) per investigator clinical judgment.
  • Recovery to baseline or ≤ Grade 2 CTCAE v5 from toxicities related to any prior treatments, unless AE(s) are clinically nonsignificant and/or stable on supportive therapy. Alopecia, sensory neuropathy Grade ≤ 2, or other Grade ≤ 2 not constituting a safety risk based on investigator's judgment are acceptable.
  • Last dose of any radiation therapy > 2 weeks before first dose of study treatment.
  • Able to provide informed consent and willing to sign an approved consent form that conforms to federal and institutional guidelines.
  • Adequate organ function as defined in the protocol

Exclusion Criteria:

  • Prior chemotherapy for metastatic urothelial carcinoma.
  • Prior chemotherapy for localized urothelial carcinoma that has been completed less than 6 months before registration.
  • Variant histologies other than urothelial carcinoma will not be allowed. Patients with a component of variant histologies will be allowed to enroll, if urothelial carcinoma is the predominant histology per investigator judgement. Patients with any component of small cell will be excluded.
  • Has received prior treatment with cabozantinib.
  • Receipt of any type of small molecule kinase inhibitor (including investigational kinase inhibitor) within 2 weeks before first dose of study treatment.
  • Receipt of any type of cytotoxic, biologic, or other systemic anticancer therapy (including investigational) within 4 weeks before first dose of study treatment.
  • Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or other checkpoint inhibitors previously.
  • Radiation therapy for bone metastasis ≤ 2 weeks, any other radiation therapy within 4 weeks before first dose of study treatment. Systemic treatment with radionuclides within 6 weeks before the first dose of study treatment. Subjects with clinically relevant ongoing complications from prior radiation therapy are not eligible.
  • Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least 4 weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability.
  • Concomitant anticoagulation with oral anticoagulants except for those specified below. Allowed anticoagulants are the following:
  • Prophylactic use of low-dose aspirin for cardioprotection (per local applicable guidelines) is permitted.
  • Low-dose low molecular weight heparins (LMWH) are permitted.
  • Therapeutic doses of LMWH or anticoagulation with direct factor Xa inhibitors rivaroxaban, edoxaban, or apixaban is allowed in subjects without known brain metastases who are on a stable dose of the anticoagulant for at least 1 week before the first dose of study treatment without, clinically significant hemorrhagic complications from the anticoagulation regimen or the tumor.
  • The subject has prothrombin time (PT)/INR or partial thromboplastin time (PTT) test ≥ 1.3 × ULN within 14 days before the first dose of study treatment.
  • The subject has uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions:
  • Cardiovascular disorders:
  • Ongoing congestive heart failure exacerbation or New York Heart Association Class 4, unstable angina pectoris, serious cardiac arrhythmias.
  • Uncontrolled hypertension defined as sustained blood pressure (BP) > 150 mm Hg systolic or > 100 mm Hg diastolic despite optimal antihypertensive treatment. Uncontrolled hypertension needs to be determined based on persistently high blood pressure readings over more than 24 hours and should NOT be based on the blood pressure readings from one clinic visit. Blood pressure readings done at home or by primary care providers are acceptable. If a blood pressure reading on the day of screening is high, but there are documented acceptable ( ≤150 mm Hg systolic and ≤100 mm Hg diastolic) blood pressure readings prior to or after the screening visit (with or without the use of anti-hypertensive medications), patient will not be considered to have uncontrolled hypertension.
  • Stroke (including transient ischemic attack [TIA]), myocardial infarction (MI), or other ischemic event, or symptomatic thromboembolic event (eg, deep venous thrombosis, pulmonary embolism) occurring less than or equal to 6 months before first dose of cabozantinib. [Note: Subjects with a diagnosis of deep vein thrombosis (DVT) or incidentally detected asympotmatic and sub-segmental pulmonary embolism (PE) on routine scans are allowed if on a stable dose of anti-coagulation for at least 1 week before first dose of study treatment].
  • Clinically significant hematuria, hematemesis, or hemoptysis of > 0.5 teaspoon (2.5 ml) of red blood, or other history of significant bleeding (eg, pulmonary hemorrhage) within 12 weeks before first dose.
  • Gastrointestinal (GI) disorders including those associated with a high risk of perforation or fistula formation:
  • The subject has evidence of tumor invading the GI tract, active peptic ulcer disease, inflammatory bowel disease (eg, Crohn's disease), diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis, acute pancreatitis, acute obstruction of the pancreatic duct or common bile duct, or gastric outlet obstruction.
  • Abdominal fistula, GI perforation, bowel obstruction, or intra-abdominal abscess within 6 months before first dose. Note: Complete healing of an intra-abdominal abscess must be confirmed before first dose.
  • Cavitating pulmonary lesion(s) or known endotracheal or endobronchial disease manifestation.
  • Lesions invading or encasing any major blood vessels.
  • Other clinically significant disorders that would preclude safe study participation per investigator clinical judgement.
  • Serious non-healing wound/ulcer/bone fracture.
  • Uncompensated/symptomatic hypothyroidism.
  • Moderate to severe hepatic impairment (Child-Pugh B or C).
  • Other severe acute or chronic medical conditions including immune colitis, inflammatory bowel disease, immune pneumonitis, pulmonary fibrosis or psychiatric conditions including recent (within the past year) or active suicidal ideation or behavior; or laboratory abnormalities that may increase the risk associated with study participation or study treatment administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study.
  • Major surgery (eg, GI surgery, removal or biopsy of brain metastasis) within 8 weeks before first dose of study treatment. Complete wound healing from major surgery must have occurred 1 month before first dose and from minor surgery (eg, simple excision, tooth extraction) at least 10 days before first dose. Subjects with clinically relevant ongoing complications per investigator clinical judgement from prior surgery are not eligible.
  • Corrected QT interval calculated by the Fridericia formula (QTcF) > 500 ms per electrocardiogram (ECG) within 28 days before first dose of study treatment. Note: If a single ECG shows a QTcF with an absolute value > 500 ms, two additional ECGs at intervals of approximately 3 min must be performed after the initial ECG, and the average of these three consecutive results for QTcF will be used to determine eligibility.
  • Diagnosis of another malignancy within 2 years before first dose of study treatment, with the exception of those determined by the treating investigator to have a negligible risk of metastasis or death (such as adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, ductal carcinoma in situ treated surgically with curative intent, localized prostate cancer treated with curative intent and/or no intent for further treatment, or incidental prostate cancer)
  • Current use of immunosuppressive medication, EXCEPT for the following: a. intranasal, inhaled, topical steroids, or local steroid injection (e.g., intra-articular injection); b. Systemic corticosteroids at physiologic doses ≤ 10 mg/day of prednisone or equivalent; c. Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication).
  • Has active autoimmune disease currently requiring systemic treatment with high dose corticosteroids (dose more than physiologic replacement doses equivalent to prednisone 10 mg daily) or (disease modifying immunosuppressive agents). Replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, intranasal, inhaled, topical steroids, or local steroid injection) is not considered an exclusion.
  • Active autoimmune disease that might deteriorate significantly when receiving an immuno-stimulatory agent per treating physician's clinical judgment. Subjects with diabetes type I, vitiligo, psoriasis, or hypo- or hyperthyroid diseases not requiring immunosuppressive treatment are eligible.
  • Prior organ transplantation including allogenic stem-cell transplantation.
  • Has known history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
  • Has an active infection currently requiring systemic (intravenous) antibiotic therapy.
  • Has a known history of active TB (Bacillus Tuberculosis).
  • Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected).
  • Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
  • Active and inactive vaccinations within 4 weeks of the first dose of pembrolizumab is prohibited.
  • Known prior severe hypersensitivity to investigational products or any component in its formulations, including known severe hypersensitivity reactions to monoclonal antibodies (NCI CTCAE v4.03 Grade ≥ 3).
  • Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment.
  • Subjects taking prohibited medications as described in Section 6.8. A washout period of prohibited medications for a period of at least two weeks or as clinically indicated should occur prior to the start of treatment.
  • Inability to swallow tablets or evidence of impaired intestinal absorption Previous systemic chemotherapy treatment for urothelial carcinoma, with the exception of perioperative chemotherapy treatment alone or with concurrent radiation within 6 months prior to treatment.

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A Phase III, Randomized, Open-Label, Controlled, Multi-Center, Global Study of First-Line Durvalumab in Combination With Standard of Care Chemotherapy and Durvalumab in Combination With Tremelimumab and Standard of Care Chemotherapy Versus Standard of Care Chemotherapy Alone in Patients With Unresectable Locally Advanced or Metastatic Urothelial Cancer.


Condition: Unresectable Locally Advanced Urothelial Cancer, Metastatic Urothelial Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03682068

Sponsor: AstraZeneca

Phase: Phase 3

Eligibility:

  • Age: minimum 18 Years maximum 130 Years
  • Gender: All

Key Inclusion Criteria:

  • Patients with histologically or cytologically documented, unresectable, locally advanced or metastatic transitional cell carcinoma (transitional cell and mixed transitional/non-transitional cell histologies) of the urothelium (including renal pelvis, ureters, urinary bladder, and urethra)
  • Patients who have not been previously treated with first-line chemotherapy. Patients who have received prior definitive chemoradiation, adjuvant or neoadjuvant treatment for locally advanced disease are eligible provided that progression to locally advanced or metastatic disease has occurred >12 months from the last therapy [for chemoradiation and adjuvant treatment] or >12 months from the last surgery [for neoadjuvant treatment].
  • At least 1 lesion, not previously irradiated, that qualifies as a RECIST 1.1 target lesion at baseline.
  • World Health Organization (WHO)/Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1 at enrolment
  • Adequate organ and marrow function as defined in the protocol
  • Life expectancy ≥12 weeks in the opinion of the investigator
  • Evidence of post-menopausal status, or negative urinary or serum pregnancy test for female pre-menopausal patients.

Key Exclusion Criteria:

  • Prior exposure to immune-mediated therapy (with exclusion of Bacillus Calmette Guerin), including but not limited to, other anti-CTLA-4, anti-PD-1, anti-PD L1, or anti-PD-L2 antibodies, except therapeutic anticancer vaccines, which are permitted. Prior local intervesical chemotherapy or immunotherapy is allowed if completed at least 28 days prior to the initiation of study treatment.
  • No severe concomitant condition that requires immunosuppression medication
  • Untreated central nervous system (CNS) metastases and/or carcinomatous meningitis
  • Patients who may be eligible for or are being considered for radical resection during the course of the study.
  • Any medical contraindications to platinum (cisplatin or carboplatin) based doublet chemotherapy and/or known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients

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Cabozantinib Plus Durvalumab in Patients With Advanced and Chemotherapy-treated Bladder Carcinoma, of Urothelial and Non-urothelial Histology: an Open-label, Single-centre, Phase 2, Single-arm Proof-of-concept Trial: ARCADIA Study


Condition: Bladder Carcinoma

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03824691

Sponsor: Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

Phase: Phase 2

Eligibility:

  • Age: minimum 18 Years maximum 90 Years
  • Gender: All

Inclusion Criteria:

  • Written informed consent.
  • Age ≥18 years.
  • Body weight >30kg
  • Histologically-confirmed diagnosis of UC or variant histologies (e.g. squamous cell carcinoma, adenocarcinoma, micropapillary tumors, BUT excluding pure small cell carcinoma) of the bladder or the urothelium.
  • Either bladder, urethral, or upper tract primary tumor will be allowed.
  • Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
  • Life expectancy of at ≥ 12 weeks.
  • Availability of tumor tissue for PD-L1 IHC assay.
  • Measurable and non-measurable disease will be included (e.g. patients with bone metastases only will be allowed for inclusion).
  • Failure of 1 or 2 cisplatin-based conventional chemotherapy regimens for metastatic disease (2nd-to-3rd line only).
  • Neoadjuvant/adjuvant regimens will be counted provided that a relapse occurred with 6 months of the last cycle of chemotherapy.
  • Adequate function of the organs: 1. Absolute neutrophil count (ANC) ≥ 1500/mm3 2. Platelets ≥ 100,000/mm3 3. Hemoglobin ≥ 9 g/dL (≥ 90 g/L). 4. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 3.0 × upper limit of normal. 5. Total bilirubin ≤ 1.5 × the upper limit of normal. For subjects with Gilbert's disease ≤ 3 mg/dL g. Serum creatinine ≤ 2.0 × upper limit of normal or calculated creatinine clearance ≥ 30 mL/min using the Cockroft-Gault equation h. Lipase < 2.0 times the upper limit of normal (ULN)
  • Recovery to baseline or ≤ Grade 1 Common Terminology Criteria for Adverse Events (CTCAE) v5.0 from toxicities related to any prior treatments, unless AE(s) are clinically nonsignificant and/or stable on supportive therapy
  • Ability to swallow tablets
  • Contraception for sexually active fertile patients and their partners. Of note, a barrier method is recommended in addition to the use of steroid hormonal contraceptives, because the effects of cabozantinib on the pharmacokinetics of the latter are unknown.
  • Evidence of post menopausal status or serum pregnancy test for female pre-menopausal subject

Exclusion Criteria:

  • Patients taking regular oral steroids, above the allowed limit of 10mg/day methylprednisolone or analogues, for any reason. Patients must not have had steroids for 28 days prior to study entry.
  • Malignancies other than bladder carcinoma within 5 years prior to Cycle 1, Day 1, with the exception of those with a negligible risk of metastasis or death and treated with expected curative outcome (such as adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, or ductal carcinoma in situ treated surgically with curative intent) or localized prostate cancer treated with curative intent and absence of prostate-specific antigen (PSA) relapse or incidental prostate cancer (Gleason score ≤ 3 + 4 and PSA < 10 ng/mL undergoing active surveillance and treatment naive).
  • Evidence of significant uncontrolled concomitant disease that could affect compliance with the protocol or interpretation of results.
  • Active or untreated CNS metastases as determined by computed tomography (CT) or magnetic resonance imaging evaluation during screening and prior radiographic assessments.
  • Patients with treated asymptomatic CNS metastases are eligible, provided they meet all of the following criteria: 1. Evaluable or measurable disease outside the CNS 2. No metastases to midbrain, pons, medulla, or within 10 mm of the optic apparatus (optic nerves and chiasm) 3. No history of intracranial or spinal cord hemorrhage 4. No ongoing requirement for corticosteroid as therapy for CNS disease; anti-convulsants at a stable dose are allowed 5. No evidence of significant vasogenic edema 6. No stereotactic radiation, whole-brain radiation or neurosurgical resection within 4 weeks prior to Cycle 1, Day 1 7. Radiographic demonstration of interim stability (i.e., no progression) between the completion of CNS-directed therapy and the screening radiographic study 8. Screening CNS radiographic study ≥ 4 weeks since completion of radiotherapy or surgical resection and ≥ 2 weeks since discontinuation of corticosteroids
  • Pregnant female patients. All female patients of childbearing potential with a positive pregnancy test within 2 weeks prior to the first dose of study treatment will be excluded from the study.
  • Clinically significant cardiovascular disease, for example, myocardial infarction (within 3months prior to enrolment), unstable angina, New York Heart Association (NYHA) grade II or greater congestive heart failure or serious cardiac arrhythmia requiring medication (beta-blockers and digoxin are allowed)
  • Uncontrolled hypertension, stroke or other ischemic or thromboembolic event (DVT, PE) within 6 months before first dose of cabozantinib.
  • Severe infections within 4 weeks prior to enrolment in the study including but not limited to hospitalization for complications of infection, bacteraemia, or severe pneumonia.
  • Major surgical procedure within 4 weeks prior to enrolmentor anticipation of need for a major surgical procedure during the course of the study other than for diagnosis. Complete wound healing from major surgery must have occurred 1 month before inclusion and from minor surgery (eg, simple excision, tooth extraction) at least 10 days before inclusion. Subjects with clinically relevant ongoing complications from prior surgery are not eligible.
  • Received therapeutic oral or intravenous (IV) antibiotics within 2 weeks prior to enrolment (patients receiving prophylactic antibiotics, e.g., for prevention of a urinary tract infection or chronic obstructive pulmonary disease, are eligible).
  • Concomitant anticoagulation with oral anticoagulants or platelet inhibitors.
  • History of autoimmune disease including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis.
  • Patients with a history of autoimmune-related hypothyroidism, unless on a stable dose of thyroid-replacement hormone.
  • Patients with uncontrolled Type 1 diabetes mellitus
  • Uncontrolled hypercalcemia (> 1.5 mmol/L ionized calcium or Ca > 12 mg/dL or corrected serum calcium > ULN) or symptomatic hypercalcemia requiring continued use of bisphosphonate therapy or denosumab. Patients who are receiving bisphosphonate therapy or denosumab specifically to prevent skeletal events and who do not have a history of clinically significant hypercalcemia are eligible. Patients who are receiving denosumab prior to enrollment must be willing and eligible to receive a bisphosphonate instead while on study.
  • radiation therapy for bone within 2 weeks or other radiation therapy within 4 weeks before first dose of study treatment. patients with clinically relevant ongoing complications from prior radiation therapy
  • serious non healing wound/ulcer/bone fracture, moderate to severe hepatic impairment (Child Pugh B or C)
  • History of idiopathic pulmonary fibrosis (including pneumonitis), drug-induced pneumonitis, organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia), or evidence of active pneumonitis on screening chest CT scan (History of radiation pneumonitis in the radiation field (fibrosis) is permitted).
  • Patients with tumors invading major pulmonary vessels and/or with cavitating pulmonary lesions.
  • Positive test for HIV.
  • Patients with active hepatitis infection (defined as having a positive hepatitis B surface antigen [HBsAg] test at screening) or hepatitis C. Patients with past hepatitis B virus (HBV) infection or resolved HBV infection (defined as having a negative HBs Ag test and a positive antibody to hepatitis B core antigen [anti-HBc] antibody test) are eligible. Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV RNA.
  • Patients with active tuberculosis.
  • Gastrointestinal disorders likely to interfere with absorption of the study drug (e.g. partial bowel obstruction or malabsorption).
  • Subjects with gastrointestinal disorders associated with a high risk of perforation or fistula formation
  • Subjects with active peptic ulcer or with a history of clinically significant GI bleeding within 12 weeks before the first dose of study treatment
  • Prior treatment with CD137 agonists, anti-PD-1, or anti-PD-L1 therapeutic antibody or pathway-targeting agents.
  • Administration of a live, attenuated vaccine within 4 weeks prior to enrolment or anticipation that such a live, attenuated vaccine will be required during the study.
  • Treatment with any other investigational agent or participation in another clinical trial with therapeutic intent within 28 days prior to enrolment.
  • Treatment with systemic immunostimulatory agents (including but not limited to interferons or interleukin [IL]-2) within 4 weeks or five half-lives of the drug, whichever is shorter, prior to enrolment.
  • Rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption

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Efficacy and Safety of Neoadjuvant Chemotherapy With Dose Dense MVAC Followed by Radical Surgery in Patients With MIBC and Locally Advanced Urothelial Carcinoma of Bladder: Phase II, Single-arm Study


Condition: Muscle Invasive Bladder Cancer, Urothelial Carcinoma, Neoadjuvant Chemotherapy

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT04047693

Sponsor: Pusan National University Yangsan Hospital

Phase: Phase 2

Eligibility:

  • Age: minimum 18 Years maximum N/A
  • Gender: All

Inclusion Criteria:

  1. Patients with histologically or cytologically confirmed urothelial cancer of bladder.
  2. Locally advanced status for planning surgical treatment (Bladder, confirm muscle invasiveness using TURBT, or cT3-4a and N1-3 using imaging studies)
  3. Age 18 years or older
  4. Eastern Cooperative Oncology Group performance status 0-1
  5. Adequate organ and bone marrow function for cisplatin based chemotherapy A. Adequate bone marrow function: Absolute Neutrophil Count (ANC) ≥ 1,500/µL, platelets ≥ 100,000/µL, hemoglobin ≥ 9 g/dL) B. Adequate renal function: creatinine < 1.5 x upper normal limit (UNL) or creatinine clearance(Ccr) using Cockroft and Gault formula ≥ 50 ml/min C. Adequate hepatic function: bilirubin < 1.5 x UNL, AST/ALT levels <5.0 x UNL, alkaline phosphatase < 5 x UNL (except in case of bone metastasis without any liver disease)
  6. Women should use contraceptive medication for 6 months after the end of the study or she would be post-menopause status. Men should consent with the contraception for 6 months after the end of the study or he would be infertile.
  7. Patients should sign a written informed consent before study entry.

Exclusion Criteria:

  1. Histologic types other than urothelial cell carcinoma should be excluded. However, urothelial cell types combined with squamous or glandular features are allowed.
  2. Excess of 4 weeks after initial imaging studies. But, allow the patients to enrollment of study if they is reassessed and reconfirm the localized status using subsequent imaging studies. In this case, clinical stage is decided as following imaging studies.
  3. Prior systemic chemotherapy (But prior intravesical chemotherapy was allowed)
  4. Peripheral sensory neuropathy grade 2 or worse according to NCI CTCAE
  5. History of treatment with drugs of another clinical trial within 30 days before enrollment.
  6. Concomitant severe medical, surgical, or psychiatric disease or problems which can affect the results of the clinical trial or have possibilities of unexpected medical problems caused be the drug of clinical trial A. Unstable angina, myocardial infarction, uncontrolled arrhythmias, symptomatic angina pectoris, cardiac failure within the previous 6 months B. Active infection which would compromise the patients C. Liver cirrohosis or chronic active hepatitis D. Poor pulmonary function (DLCO ≤ 50% of normal or resting O2 saturation ≤ 90%) E. Clinically significant hemoptysis or gastrointestinal bleeding within previous 6 months F. Major psychiatric disorders or other inadequate psychiatric problems according to the physicians decision
  7. History of another malignancy (but treated malignancy at least two years before enrollment were allowed, and cured non-melanoma skin cancer, any cured in-situ carcinoma, clinically insignificant localized prostate cancer, or papillary thyroid carcinoma are allowed even diagnosed less than 2 years before enrollment).
  8. Pregnant or lactating women, women of childbearing potential not employing adequate contraception

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Phase I Study of Avelumab in Combination With AXL Inhibitor AVB-S6-500 in Patients With Advanced Urothelial Carcinoma


Condition: Urothelial Carcinoma

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT04004442

Sponsor: University of Oklahoma

Phase: Phase 1

Eligibility:

  • Age: minimum 18 Years maximum N/A
  • Gender: All

Inclusion Criteria:

  1. Age ≥18 years
  2. Histologically confirmed locally advanced unresectable (T4b or N2/N3 disease) or metastatic urothelial cancer (including renal pelvis, ureters, urinary bladder, urethra).
  3. Eligible patients must have had either:
  4. Progressed after treatment with at least 1 prior platinum-containing regimen, (e.g., received at least 2 cycles of cisplatin or carboplatin-based regimen) for inoperable locally advanced unresectable or metastatic urothelial carcinoma, OR OR
  5. Experienced disease progression or recurrence within 12 months of completion of neoadjuvant or adjuvant cisplatin-based chemotherapy, OR OR
  6. Ineligible for cisplatin-based chemotherapy due to eastern co-operative oncology group (ECOG) performance status 2, grade ≥2 neuropathy, GFR<60 mL/min, grade ≥2 hearing loss or New York Heart Association class III or worse congestive heart failure.
  7. Declined platinum (cisplatin or carboplatin) based chemotherapy after informed discussion with the treating investigator
  8. Available pretreatment baseline tumor specimen or willingness to undergo biopsy of primary or metastatic lesion if archived specimen is not available.
  9. ECOG performance status of ≤2
  10. At least one measurable lesion by RECIST version 1.1
  11. Patients who are able to understand and sign the informed consent form.
  12. Ability to comply with protocol
  13. Adequate hematologic and end-organ function per protocol
  14. For women of childbearing potential: Negative serum or urine pregnancy test at screening.
  15. For both male and female subjects: agreement to remain abstinent (refrain from heterosexual intercourse) or use highly effective contraceptive methods that result in a failure rate of <1% per year during the treatment period and for at least 30 days after the last dose of study drug

Exclusion Criteria:

  1. Concurrent systemic treatment with an anticancer treatment or investigational drug within 28 days. Palliative radiation to symptomatic primary tumor or metastases is permitted as long as there are other measurable lesions present outside of the radiation field.
  2. Prior therapy with anti-PD-1 or PD-L1 agents.
  3. Concurrent systemic therapy with corticosteroids (>10 mg prednisone equivalent) or other immunosuppressive agents within 28 days before starting trial drug. Short-term administration of systemic steroids (less than 7 days), adrenal replacement steroid doses (≤10 mg daily prednisone equivalent), topical, intranasal and inhaled steroid use is permitted.
  4. Patients with untreated or symptomatic central nervous metastases will be excluded. Patients appropriately treated with either surgery and/or radiation therapy will be eligible to participate in the study 4 weeks after completion of radiation/surgery and if follow up brain imaging after CNS directed therapy demonstrates stability or improvement in brain metastases.
  5. Active second malignancy or previous history of malignant disease (other than urothelial carcinoma) diagnosed within the last 3 years, with the exclusion of basal or squamous cell carcinoma of the skin, cervical carcinoma in situ and pT2 prostate adenocarcinoma with Gleason score ≤7 (with no dominant pattern 4).
  6. Prior organ transplantation, including allogenic stem-cell transplantation.
  7. Known history of HBV infection (including acute and chronic infection) and untreated hepatitis C. Patients with treated HCV infection will be eligible.
  8. Known hypersensitivity to monoclonal antibody or any biologic drug, history of anaphylaxis, or uncontrolled asthma.
  9. Persisting toxicity related to prior therapy that was > grade 1 according to NCI-CTCAE v4; grade ≤2 sensory neuropathy is allowed.
  10. Pregnant or lactating, or intending to become pregnant during the study a. Women who are not postmenopausal (≥ 12 months of non-therapy-induced amenorrhea) or surgically sterile must have a negative pregnancy test result within 14 days prior to the first dose of study treatment.
  11. Diagnosis of active autoimmune disease requiring systemic immunosuppression. Patients with type 1 diabetes, vitiligo, psoriasis, hypo- or hyperthyroid disease not requiring systemic immunosuppression are eligible.
  12. History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan. a. History of radiation fibrosis in the radiation field (fibrosis) is permitted.
  13. Active infection requiring systemic therapy.
  14. Severe infections within 4 weeks prior to the first dose of study treatment, including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia
  15. Administration of a live/attenuated vaccine within 4 weeks prior to the first dose of study treatment, within 5 months following the administration of the last dose of study drug, or anticipation that such a live/attenuated vaccine will be required during the study.
  16. Other severe acute or chronic medical conditions including immune colitis, inflammatory bowel disease, immune pneumonitis, pulmonary fibrosis or psychiatric conditions including recent (within the past year) or active suicidal ideation or behavior; or laboratory abnormalities that may increase the risk associated with study participation or study treatment administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study.

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A Phase II Study of Intermittent Checkpoint Inhibitor Therapy in Patients With Advanced Urothelial Carcinoma


Condition: Urothelial Carcinoma

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT04322643

Sponsor: Case Comprehensive Cancer Center

Phase: Phase 2

Eligibility:

  • Age: minimum 18 Years maximum N/A
  • Gender: All

Inclusion Criteria:

  • Men and women ≥ 18 years of age.
  • Histological confirmation of urothelial carcinoma (any histology)
  • Advanced or metastatic urothelial carcinoma.
  • Measurable disease as defined by RECIST 1.1 criteria
  • Has received at least 24 weeks (+/- 4 weeks) on CPI therapy per standard of care (SOC) for advanced urothelial carcinoma
  • Karnofsky Performance Score (KPS) ≥70% (for more information on KPS, please see: http://www.npcrc.org/files/news/karnofsky_performance_scale.pdf)
  • Willing and able to provide informed consent.
  • Laboratory criteria for study entry must meet the following criteria:
  • Serum creatinine ≤ 2 x ULN OR CrCl ≥ 30 mL/min (measured or calculated using the Cockcroft-Gault formula).
  • Hb ≥ 8.0g/dL
  • AST and ALT ≤ 3.0 x ULN
  • Bilirubin ≤ 1.5 x ULN (except subjects with Gilbert Syndrome, who can have total bilirubin < 3.0 mg/dL)

Exclusion Criteria:

  • History of severe hypersensitivity reaction to any monoclonal antibody.
  • Patients are excluded if they have known HIV/AIDS.
  • Major surgery (eg, cystectomy) less than 28 days prior to the first dose of study drug.
  • Any condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 7 days prior to the first dose of study drug. Inhaled steroids and adrenal replacement steroid doses > 10 mg daily prednisone equivalent are permitted in the absence of active autoimmune disease.
  • Known medical condition (eg, a condition associated with diarrhea or acute diverticulitis) that, in the investigator's opinion, would increase the risk associated with study participation or study drug administration or interfere with the interpretation of safety results.
  • Pregnant women are excluded from this study because animal studies have demonstrated that PD-1/PD-L1 inhibitors can cause fetal harm when administered to pregnant women. Breastfeeding women are excluded from this study because PD-1/PD-L1 inhibitors may be excreted in human milk and the potential for serious adverse reactions in nursing infants.

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Bladder Cancer Longitudinal Biorepository for Development of Novel Therapeutics/Biomarkers


Condition: Bladder Cancer

Study Type: Observational [Patient Registry]

Clinical Trials Identifier NCT 8-digits: NCT03413982

Sponsor: University of Kansas Medical Center

Phase:

Eligibility:

  • Age: minimum 18 Years maximum N/A
  • Gender: All

Inclusion Criteria:

  • Patients who present to clinic with presumed bladder cancer or have a diagnosis of bladder cancer are eligible to participate
  • Patients can participate in any additional research studies during the patients' participation within this protocol.

Exclusion Criteria:

  • Patients who do not have presumed bladder cancer will not be eligible

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Randomized Clinical Trial of Intracorporeal vs Extracorporeal Urinary Diversion After Robot Assisted Radical Cystectomy


Condition: Bladder Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03469362

Sponsor: University of Miami

Eligibility:

  • Age: minimum 18 Years maximum 99 Years
  • Gender: All

Inclusion Criteria:

  • Biopsy-proven urothelial cancer being considered for RARC.
  • Clinical stage T1-T4, N0-1, M0 or refractory carcinoma in situ.
  • Subject must be already scheduled to have a RARC at the discretion of the surgeon and with the patient's agreement.

Exclusion Criteria:

  • Inability to give informed consent
  • Prior major abdominal and pelvic open surgical procedures that would preclude a safe robotic approach, as determined by the treating surgeon.
  • At the discretion of the treating surgeon, any pre-existing condition such as severe chronic obstructive pulmonary disease that precludes a safe initiation or maintenance of pneumoperitoneum over a prolonged period of time and during surgery.
  • Age <18 or >99 years.

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