Bladder Cancer

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A Phase I Open Label Study of GSK3359609 Administered Alone and in Combination With Anticancer Agents in Subjects With Selected Advanced Solid Tumors


Condition: Neoplasms

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT02723955

Sponsor: GlaxoSmithKline

Phase: Phase 1

Eligibility:

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

Inclusion Criteria:

  • Capable of giving signed, written informed consent.
  • Male or female, age >=18 years (at the time consent is obtained).
  • Histological or cytological documentation of an invasive malignancy that was diagnosed as locally advanced/metastatic or relapsed/refractory and is of one of the following tumor types: bladder/urothelial cancer of the upper and lower urinary tract; cervical; colorectal (includes appendix); esophagus, squamous cell; head and neck carcinoma; melanoma; malignant pleural mesothelioma (MPM); non-small-cell lung cancer (NSCLC), prostate; Microsatellite Instability-High/deficient mismatch repair (MSI-H/dMMR) tumor (Part 1B and Part 2B) and Human Papilloma Virus (HPV)-positive or Epstein-Barr (EBV)-positive tumor (Part 1B and Part 2B).
  • Disease that has progressed after standard therapy for the specific tumor type, or for which standard therapy has proven to be ineffective, intolerable, or is considered inappropriate, or if no further standard therapy exists; exceptions are in these tumor types in which pembrolizumab single agent may be a standard: NSCLC, head and neck squamous cell cancer (HNSCC), bladder/urothelial cancer, MSI-H/dMMR cancers and melanoma and cervical cancer. In Part 2B pembrolizumab combination expansion cohorts, prior treatment with anti-Programmed cell death protein 1(PD-1)/ Ligand-1 (L1) may not be required. 1) Participants must not have received more than 5 prior lines of therapy for advanced disease including both standards of care and investigational therapies. 2) Participants who received prior PD-1/L1 therapy must fulfill the following requirements (Part 1B [except PK/PD cohort]/ Part 2B):a) Have achieved a CR, PR or SD and subsequently had disease progression while still on PD-1/L1 therapy; b) Have received at least 2 doses of an approved PD-1/L1 inhibitor (by any regulatory authority), c) Have demonstrated disease progression as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 within 18 weeks from the last dose of the PD-1/L1 inhibitor. The initial evidence of disease progression is to be confirmed by a second assessment no less than four weeks from the date of the first documented Progressive Disease (PD) (the confirmatory scan could be the Baseline eligibility scan for this study). 3) In Part 2A 5-fluorouracil (FU)/platinum combination with GSK3359609 and pembrolizumab cohort, participants must not have received prior systemic therapy administered in the recurrent or metastatic setting (with the exception of systemic therapy given as part of multimodal treatment for locally advanced disease).
  • Archival tumor tissue obtained at any time from the initial diagnosis to study entry; a fresh tumor biopsy using a procedure that is safe for the participant on a lesion not previously irradiated unless lesion progressed will be required if archival tissue is unavailable.
  • Agree to undergo a pre-treatment and on treatment biopsy and have disease amenable to biopsy required in pharmacokinetic (PK) / pharmacodynamics (PD), dose randomized HNSCC, Melanoma dose expansion and Biomarker cohorts..
  • Measurable disease per RECIST version 1.1. Palpable lesions that are not measurable by radiographic or photographic evaluations may not be utilized as the only measurable lesion. Any measurable lesion biopsied at Screening cannot be followed as a target/index lesion unless agreed upon by GlaxoSmithKline (GSK).
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1.
  • Life expectancy of at least 12 weeks.
  • Adequate organ function.
  • QT interval corrected for heart rate according to Fridericia's formula (QTcF) <450 milliseconds (msec) or QTcF <480 msec for participants with bundle branch block.
  • A female participant is eligible to participate if she is not pregnant (as confirmed by a negative serum beta-human chorionic gonadotrophin [beta-hCG] test in females of reproductive potential), and not lactating or reproductive potential agrees to follow one of the options listed in protocol from 30 days prior to the first dose of study medication and until 120 days after the last dose of study treatment.
  • Male participants with female partners of child bearing potential must agree to use one of the methods of contraception specified in protocol from time of first dose of study treatment until 120 days after the last dose of study treatment.
  • Documented HPV/ EBV-positive tumor as determined by a local laboratory for Part 1B and Part 2B pembrolizumab combination viral-positive expansion cohorts only.
  • Documented MSI-H or dMMR-positive tumor as determined by local laboratory for Part 1B and Part 2B pembrolizumab combination MSI-H/dMMR expansion cohorts only.
  • Documented ICOS expression using an analytically validated immunohistochemistry (IHC) assay by central laboratory for Part 1B biomarker cohort only.
  • Documented gene expression (GEX) result using an analytically validated method by central laboratory (Part 1B Biomarker Cohort only).
  • PD-L1 combined positive score (CPS) <1 using the Food and Drug Administration (FDA) approved PD-L1 IHC 22C3 pharmdx assay by central laboratory testing for Part 2B HNSCC PD-L1 CPS <1 Cohort. Documented test result from FDA approved PD-L1 IHC 22C3 pharmDx assay in local laboratory, if available, may be accepted in lieu of the central laboratory test result.
  • Defined PD-L1 expression using the Ventana PD-L1 (SP263) IHC assay by central testing for enrollment in the PK/PD cohort with bintrafusp alfa, dostarlimab, dostarlimab and cobolimab combination studies (Part 2A).

Exclusion Criteria:

  • Prior treatment with the following therapies:
  • Anticancer therapy within 30 days or 5 half-lives of the drug, whichever is shorter. At least 14 days must have elapsed between the last dose of prior anticancer agent and the first dose of study drug is administered.
  • Part 2B (GSK3359609/pembrolizumab combination): prior pembrolizumab washout is not required.
  • Prior radiation therapy: permissible if at least one non-irradiated measurable lesion is available for assessment according to RECIST version 1.1 or if a solitary measurable lesion was irradiated, objective progression is documented. A wash out of at least two weeks before start of study drug for radiation of any intended use to the extremities for bone metastases and 4 weeks for radiation to the chest, brain, or visceral organs is required. • Investigational therapy within 30 days or 5 half-lives of the investigational product (whichever is shorter). At least 14 days must have elapsed between the last dose of investigational agent and the first dose of study drug is administered.
  • Prior allogeneic or autologous bone marrow transplantation or other solid organ transplantation.
  • Toxicity from previous anticancer treatment
  • Invasive malignancy or history of invasive malignancy other than disease under study within the last two years except: Any other invasive malignancy for which the participant was definitively treated, has been disease-free for <=2 years and in the opinion of the principal investigator and GSK Medical Monitor will not affect the evaluation of the effects of the study treatment on the currently targeted malignancy, may be included in this clinical trial; and curatively treated non-melanoma skin cancer.
  • Central nervous system (CNS) metastases, with the following exception: • Participants who have previously-treated CNS metastases, are asymptomatic, and have no requirement for steroids at least 14 days prior to first dose of study drug. Participants with carcinomatous meningitis or leptomeningeal spread are excluded regardless of clinical stability.
  • Received transfusion of blood products (including platelets or red blood cells) or administration of colony stimulating factors (including granulocyte colony-stimulating factor [G-CSF], granulocyte-macrophage colony-stimulating factor, recombinant erythropoietin) within 14 days prior to the first dose of GSK3359609.
  • Major surgery <=4 weeks before the first dose of study treatment. Participants must have also fully recovered from any surgery (major or minor) and/or its complications before initiating study treatment.
  • Active autoimmune disease that has required systemic treatment within the last two years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
  • Concurrent medical condition requiring the use of systemic immunosuppressive medications within 7 days before the first dose of study treatment. Physiologic doses of corticosteroids for treatment of endocrinopathies or steroids with minimal systemic absorption, including topical, inhaled, or intranasal corticosteroids may be continued if the participant is on a stable dose.
  • Condition requiring treatment with strong inhibitors/inducers of cytochrome (CYP) p450 3A4 within 7 days prior to first dose of chemotherapy (requirement applies to participants enrolled to Part 2 chemotherapy combination with docetaxel).
  • Active infection requiring systemic therapy, known human immunodeficiency virus infection, or positive test for hepatitis B active infection or hepatitis C active infection.
  • Current active liver or biliary disease (with the exception of Gilbert's syndrome or asymptomatic gallstones, liver metastases, or otherwise stable chronic liver disease per investigator assessment).
  • Recent history (within the past 6 months) of acute diverticulitis, inflammatory bowel disease, intra-abdominal abscess, or gastrointestinal obstruction that required surgery.
  • Receipt of any live vaccine within 4 weeks prior to first dose of study treatment.
  • Recent history of allergen desensitization therapy within 4 weeks of starting study treatment.
  • History of severe hypersensitivity to monoclonal antibodies or to the chemotherapies under investigation including any ingredient used in the formulation.
  • History or evidence of cardiac abnormalities.
  • History of (current and past) idiopathic pulmonary fibrosis, pneumonitis (for past pneumonitis exclusion only if steroids were required for treatment), interstitial lung disease, or organizing pneumonia. Note: post-radiation changes in the lung related to prior radiotherapy and/or asymptomatic radiation-induced pneumonitis not requiring treatment may be permitted if agreed by the investigator and Medical Monitor.
  • Recent history (within 6 months) of uncontrolled symptomatic ascites or pleural effusions.
  • Any serious and/or unstable pre-existing medical, psychiatric disorder, or other condition that could interfere with the participant's safety, obtaining informed consent, or compliance to the study procedures.

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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 Corp.

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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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 (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 in the upper urinary tract within 2 months prior to inclusion
  • Systemic chemotherapy treatment within 2 months prior to enrollment
  • Prohibited medication that could not be adjusted or discontinued prior to study treatment
  • 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 TOOKAD 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, 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 disease types other than breast cancer, biliary tract cancer, non-squamous NSCLC, and cervical cancer: Disease progression on or after the most recent systemic therapy for locally-advanced unresectable or metastatic disease
  • Participants with any breast cancer subtype:
  • Must have HER2-mutated disease which does not display HER2 overexpression/amplification
  • Must have progressed on or after ≥1 prior line of treatment (chemotherapy, endocrine therapy, or targeted therapy) for locally-advanced unresectable or metastatic breast cancer
  • Participants with metastatic HR+ HER2-mutated disease must have received a prior CDK4/6 inhibitor in the metastatic setting.
  • Participants with biliary tract cancer: must have completed ≥1 prior line of treatment (chemotherapy, endocrine therapy, or targeted therapy)
  • Participants with non-squamous NSCLC: has relapsed from or is refractory to standard treatment or for which no standard treatment is available
  • Participants with cervical cancer:
  • Participants with metastatic cervical cancer must have progressed on or after ≥1 prior line of systemic therapy in the metastatic setting.
  • Participants with locally advanced unresectable cervical cancer must have progressed on or after ≥1 prior lines 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, GEC, or CRC whose disease shows HER2 amplification/overexpression.
  • Previous treatment with HER2-directed therapy; participants with uterine serous carcinoma 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, 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, GEC, or CRC whose disease shows HER2 amplification/overexpression.
  • Previous treatment with HER2-directed therapy; participants with uterine serous carcinoma 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, 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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A Randomized, Controlled, Open-Label Study of the Efficacy, Durability, and Safety of UGN-102 With or Without TURBT in Patients With Low Grade Intermediate Risk Non-Muscle-Invasive Bladder Cancer (LG IR NMIBC)


Condition: Bladder Cancer, Urothelial Carcinoma, Urothelial Carcinoma Bladder

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT04688931

Sponsor: UroGen Pharma Ltd.

Phase: Phase 3

Eligibility:

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

Inclusion Criteria:

  • 1. Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in 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 of screening. 3. Is at intermediate risk for progression, 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). 4. Negative voiding cytology for high grade (HG) disease within 6 weeks of screening. 5. Has adequate organ and bone marrow function as determined by the following routine laboratory tests:
  • Leukocytes ≥ 3,000 cells per μL;
  • Absolute neutrophil count ≥ 1,500 cells per μL;
  • Platelets ≥ 100,000 per μL;
  • Hemoglobin ≥ 9.0 g/dL;
  • Total bilirubin ≤ 1.5 x upper limit of normal (ULN);
  • Aspartate aminotransferase (AST) and 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). 7. 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 enrollment through 6 months post-treatment.

Exclusion Criteria:

  • 1. History of carcinoma in situ (CIS) on preliminary cystoscopy within 5 years of enrollment. 2. Received Bacillus Calmette-Guérin (BCG) treatment for urothelial carcinoma (UC) within previous 1 year. 3. History of HG papillary UC in the past 2 years. 4. Known allergy or sensitivity to mitomycin that in the investigator's opinion cannot be readily managed. 5. Clinically significant urethral stricture that would preclude passage of a urethral catheter. 6. History of pelvic radiotherapy. 7. History of:
  • Neurogenic bladder;
  • Active urinary retention;
  • Any other condition that would prohibit normal voiding. 8. Past or current muscle invasive (ie, T2, T3, T4) or metastatic UC or concurrent upper tract UC. 9. Current tumor grading of T1. 10. 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. 11. History of prior treatment with an intravesical chemotherapeutic agent except for a single dose of chemotherapy immediately post any previous TURBT. 12. Has previously participated in a study in which they received UGN-102. 13. Has participated in a study with an investigational agent or device within 30 days of randomization.

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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 (TROPiCS-04)


Condition: Urothelial Carcinoma, Bladder Cancer, Metastatic Urothelial Carcinoma, Locally Advanced Urothelial Cancer, Transitional Cell Carcinoma

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT04527991

Sponsor: Immunomedics, Inc.

Phase: Phase 3

Eligibility:

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

Inclusion Criteria:

  1. Female or male subjects, ≥18 years of age, able to understand and give written informed consent.
  2. Subjects 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.
  3. ECOG performance status (PS) score of 0 or
  4. Subjects with progression or recurrence following receipt of platinum-containing regimen and anti PD-1/PD-L1 therapy for metastatic or locally advanced unresectable disease will be enrolled.
  5. Subjects 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 subjects must receive anti PD-1/PD-L1 therapy in the metastatic or locally advanced unresectable setting to be eligible.
  6. Subjects 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.
  7. Cisplatin ineligible subjects 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:
  8. Creatinine Clearance <60 mL/min
  9. Grade ≥2 Audiometric Hearing Loss
  10. Grade ≥2 Peripheral Neuropathy
  11. New York Heart Association (NYHA) Class III heart failure
  12. ECOG PS ≥2 d. Anti PD-1/PD-L1 therapy administered as part of maintenance therapy may be counted towards eligibility for the study Subjects 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.
  13. Subjects 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.
  14. Adequate hematologic counts without transfusion or growth factor support within 1 week of study drug initiation (hemoglobin ≥9 g/dL, absolute neutrophil count [ANC] ≥1,500/mm3, and platelets ≥100,000/µL).
  15. 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 subjects 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.
  16. 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).
  17. 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 drug. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
  18. 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 drug. Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for >2 years.
  19. Male subjects must agree to use an adequate method of contraception starting with the first dose of study therapy through 3 months after the last dose of study therapy.

Exclusion Criteria:

  • 1. Women who are pregnant or lactating. 2. Have had a prior anti-cancer mAb/ ADC within 4 weeks prior to 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. 3. Have received prior chemotherapy for UC with all 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 an approved therapy). 4. Have not recovered (i.e., ≤Grade 1) from AEs due to previously administered chemotherapeutic agent.
  • Note: Subjects with ≤Grade 2 neuropathy or any grade of alopecia are an exception to this criterion and will qualify for the study.
  • Note: If subjects 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: Subjects with a history of malignancy that have been completely treated and with no evidence of active cancer for 3 years prior to enrollment, or subjects 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: 1. Myocardial infarction or unstable angina pectoris within 6 months of C1D1. 2. 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. 3. 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 subjects with a history of HBV or HCV, subjects 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 or unable or unwilling to receive the doses specified in the protocol. 14. Have inability to complete all specified study procedures for any reason.

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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 Corp.

Phase: Phase 3

Eligibility:

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

Inclusion Criteria:

  • Has a histologically confirmed 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 co-inhibitory 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 prior to the first dose of study drug
  • Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study intervention
  • Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or the selected chemotherapy regimen, and/or any of their excipients
  • 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 prior to the first dose of study drug
  • 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

Inclusion Criteria:

  • 1. Have histologically or cytologically confirmed, invasive urothelial carcinoma with susceptible FGFR3 alterations within 120 days following nephroureterectomy, distal ureterectomy, or cystectomy 2. If the patient received neoadjuvant chemotherapy, pathologic stage at surgical resection must be AJCC Stage ≥ ypT2 and/or yN+. 3. If the patient did not receive neoadjuvant chemotherapy: 1. Must be ineligible to receive cisplatin-based adjuvant chemotherapy per the Galsky criteria:
  • creatinine clearance < 60cc/min or
  • ≥ Grade 2 hearing loss or
  • ≥ Grade 2 neuropathy) 2. Pathologic stage must be AJCC Stage ≥pT2 pN0-2 M0 (post-lymphadenectomy or no lymphadenectomy [pNx]) for upper tract disease. 3. Pathologic stage should be AJCC Stage ≥pT3 or pN+ (bladder cancer). 4. Have Eastern Cooperative Oncology Group (ECOG) performance status of ≤2. 5. Patients must have no evidence of metastatic disease based on screening CT or MRI.

Exclusion Criteria:

  1. Presence of positive surgical margins following nephroureterectomy, distal ureterectomy, or cystectomy.
  2. Have received Bacillus Calmette-Guerin (BCG) or other intravesical therapy for Non-Muscle Invasive Bladder Cancer (NMIBC) within the previous 30 days.
  3. Have previously or currently is receiving treatment with a mitogen-activated protein kinase (MEK) or selective FGFR inhibitor.
  4. Have impaired gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral infigratinib (eg, active ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, small bowel resection)
  5. Have current evidence of corneal or retinal disorder/keratopathy.
  6. Have a history and/or current evidence of extensive tissue calcification.
  7. Have current evidence of endocrine alterations of calcium/phosphate homeostasis (eg, parathyroid disorders, history of parathyroidectomy, tumor lysis, tumoral calcinosis), unless well controlled.
  8. Are currently receiving or are planning to receive during participation in this study, treatment with agents that are known strong inducers or inhibitors of CYP3A4 and medications which increase serum phosphorus and/or calcium concentration.
  9. Clinically significant cardiac disease.
  10. Recent (< 3 months prior to first dose of study drug) transient ischemic attack or stroke.

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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/II 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 2

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
  5. Unable to tolerate platinum (cisplatin or carboplatin) based chemotherapy due to toxicity, OR
  6. Experienced disease progression or recurrence within 12 months of completion of neoadjuvant or adjuvant cisplatin-based chemotherapy, OR
  7. Ineligible for cisplatin-based chemotherapy due to eastern co-operative oncology group (ECOG) performance status 2, grade ≥2 neuropathy, GFR<60 mL/Hr, grade ≥2 hearing loss and New York Heart Association class III or worse congestive heart failure.
  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. Appropriately treated CNS metastases with either surgery or radiation therapy are permitted to participate in the study.
  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 prostate adenocarcinoma with Gleason score ≤7, pT2b.
  6. Prior organ transplantation, including allogenic stem-cell transplantation.
  7. Known history of testing positive for HIV/AIDS, HBV, or HCV (including acute and chronic infection).
  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; 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 pneumonitis 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 per protocol

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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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Intravesical Ty21a for the Treatment of Patients With Non-muscle-invasive Bladder Cancer (NMIBC)


Condition: Non Muscle Invasive Bladder Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03421236

Sponsor: Patrice Jichlinski

Phase: Phase 1

Eligibility:

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

Inclusion Criteria:

  • Patients with an intermediary or low risk of progression of bladder cancer (according to an EORTC score and clinical considerations) and thus not requiring BCG immunotherapy will be included after a transurethral resection of the bladder tumor (TURBT). Male and Female patients aged > 18yrs, with a Karnofsky performance status of 60% or more, sero-negative for HIV, HBV and HCV and with laboratory parameters for vital function in the normal range or with abnormalities without clinical significance may be included.

Exclusion Criteria:

  • Patients with NMIBC that require BCG treatments or with muscle-invasive bladder cancer, sero-positive for HIV, HBV and HCV or with other serious illnesses (e.g., serious infections requiring antibiotics, bleeding disorders, autoimmune disease), will be excluded.

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SArcopenia, Mobility, PHYsical Activity and Post-operative Risk of Bladder Carcinoma in the Elderly


Condition: Sarcopenia, Bladder Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03362801

Sponsor: University Hospital, Caen

Eligibility:

  • Age: minimum 65 Years maximum N/A
  • Gender: All

Inclusion Criteria:

  • confirmed urothelial bladder carcinoma ( RTUV)
  • indication of radical cystectomy
  • Able, informed and with informed consent for the study
  • affiliated to the social security system
  • talking French

Exclusion Criteria:

  • Life expectancy <6 months
  • other active malignant tumors or other severe concomitant chronic pathologies affecting the general condition of the patient and / or likely to limit compliance with the requirements of the study.
  • treatments incompatible with the study: previous corticosteroid treatment prolonged for more than one month (induces iatrogenic sarcopenia).

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