Bladder Cancer

{{header-clinical-trials-navigation}}

A Phase I Single-Arm Study of the Combination of Durvalumab (MEDI4736) and Vicineum (Oportuzumab Monatox, VB4-845) in Subjects With High-Grade Non-Muscle-Invasive Bladder Cancer Previously Treated With Bacillus Calmette-Gu(SqrRoot)(Copyright)Rin (BCG)


Condition: Urinary Bladder Neoplasms

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03258593

Sponsor: National Cancer Institute (NCI)

Phase: Phase 1

Eligibility:

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

Inclusion Criteria:

  • Patients must have histologically or cytologically confirmed by NCI Laboratory of Pathology as high grade non-muscle invasive urothelial (transitional cell carcinoma) of the bladder as follows:
  • Carcinoma-in-situ (CIS) with or without papillary tumors
  • High-grade Ta or T1 disease based on a biopsy/TURBT performed within 12 weeks of the initial dose of study treatment. If multiple bladder biopsies/TURBTs are required to confirm eligibility, the timing of the last bladder biopsy to the initial dose of study treatment must be within 12 weeks.
  • Patients with persistent T1 high grade disease on TURBT following a single induction course of BCG (at least 5 of 6 doses) may also be eligible for this trial provided that the patient is surgically unfit for cystectomy as deemed by the investigator or the patient declines cystectomy.
  • Subjects with BCG unresponsive disease as defined by the Society of Urologic Oncology and the FDA: Subjects must have received at least two courses of intravesical BCG (at least 5 of 6 induction doses of BCG and at least 2 of 3 maintenance doses of BCG under a maintenance regimen or at least 2 doses of a repeat induction course). Please note exception above for persistent T1 disease. There is no upper limit on the amount of prior BCG a subject may have received.
  • Patients who have met eligibility criterion above must have received last BCG dose within a year of enrollment.
  • The investigator must document that he/she believes the subject would not benefit from additional BCG treatment at the time of study entry.
  • Age >= 18 years at time of signing the informed consent form (ICF). Because no dosing or adverse event data are currently available on the use of Vicineum in combination with durvalumab in patients <18 years of age, children are excluded from this study, but will be eligible for future pediatric trials. Furthermore, NMIBC does not occur in children.
  • Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
  • Adequate organ and marrow function as defined below:
  • Hemoglobin >= 9.0 g/dL
  • Absolute neutrophil count (ANC) >= 1.5 x 10^9/L (> 1500 per mm^3)
  • Platelet count >= 75 x 10^9/L (>75,000 per mm^3)
  • Serum bilirubin less than or equal to 1.5 x institutional upper limit of normal (ULN).
  • AST (SGOT)/ALT (SGPT) less than or equal to 2.5 x institutional ULN
  • Creatinine CL>40 mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976) or by 24-hour urine collection for determination of creatinine clearance:
  • Males: Creatinine CL (mL/min) = (Weight (kg) x (140
  • Age))/72 x serum creatinine (mg/dL)
  • Females: Creatinine CL (mL/min)= (Weight (kg) x (140
  • Age) x 0.85 )/72 x serum creatinine (mg/dL)
  • Female subjects must either be of non-reproductive potential (i.e., post-menopausal as described below) OR history of surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or must have a negative serum pregnancy test upon study entry.
  • Women <50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution
  • Women >= 50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced menopause with last menses >1 year ago, or had chemotherapy-induced menopause with last menses >1 year ago
  • The effects of Vicineum and durvalumab on the developing human fetus are unknown. For this reason, all sexually active subjects agree to use barrier contraception (i.e., condoms) while receiving study treatment and for 120 days following their last dose of study treatment. Female subjects of child-bearing potential and male subjects whose sexual partners are WOCBP agree to use barrier contraception and a second form of contraception while receiving study treatment and for 4 months following their last dose of study treatment. 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.
  • Written informed consent obtained from the subject prior to performing any protocol- related procedures
  • Subject is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.
  • Body weight > 30 kg

Exclusion Criteria:

  • Patients who are receiving any other investigational agents.
  • QT interval corrected for heart rate using Fridericia s formula (QTcF) >=470 ms. (Any clinically significant abnormalities detected require triplicate ECG results and a mean QT interval corrected for heart rate using Fridericia s formula (QTcF) >=470 ms calculated from 3 ECGs.)
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to Vicineum or durvalumab or other agents used in the study.
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. Urinary tract infections (UTIs) are excluded from being an exclusion criterion for treatment unless they are grade 3 or higher.
  • Pregnant women are excluded from this study because it is unknown whether Vicineum and/or durvalumab have any teratogenic effects. In nursing mothers, breastfeeding should be discontinued as these medications may have the potential risk for adverse events in nursing infants secondary to treatment of the mother.
  • Any previous treatment with a PD1 or PD-L1 inhibitor, including durvalumab
  • Evidence of non-bladder urothelial (transitional cell) carcinoma by biopsy, cytology, or radiological imaging within the past 2 years of treatment (e.g. upper tract transitional cell carcinoma, urethral urothelial carcinoma).
  • Subjects with hydronephrosis, except for those subjects where hydronephrosis has been longstanding (i.e., predates the diagnosis of the CIS, Ta, or T1 by more than 2 years) and diagnostic evaluation at screening shows no evidence of tumor causing the hydronephrosis.
  • Any other anticancer therapy (e.g., chemotherapy, biologic therapy, immunotherapy, targeted therapy, endocrine therapy, radiation therapy, intravesical therapy, investigational agent) within 28 days of the first dose of study therapy (and within 6 weeks for nitrosourea or mitomycin C) other than a single dose of intravesical chemotherapy which is permitted between 28 days and 14 days prior to the first dose of study treatment.
  • The subject has a diagnosis of another malignancy within 2 years before the first dose of study treatment, except for superficial skin cancer, localized prostate cancer on active surveillance, or localized solid tumors deemed cured by surgery and not treated with systemic anticancer therapy and not expected to require anticancer therapy in the next 2 years i.e., while the subject may be taking study treatment.
  • Current or prior use of immunosuppressive medication within 28 days before the first dose of durvalumab, with the exceptions of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid.
  • Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [e.g. colitis or Crohn s disease], diverticulitis [with the exception of diverticulosis], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome [granulomatosis with polyangiitis, Graves disease, rheumatoid arthritis, hypophysitis, uveitis, etc.]). The following are exceptions to this criterion:
  • Subjects with vitiligo or alopecia
  • Subjects with hypothyroidism (e.g. following Hashimoto syndrome) stable on hormonal replacement
  • Any chronic skin condition that does not require systemic therapy
  • Subjects without active disease in the last 5 years may be included but only after consultation with the Principal Investigator
  • Subjects with celiac disease controlled by diet alone
  • History of primary immunodeficiency.
  • History of allogeneic organ transplant.
  • History of hypersensitivity to durvalumab or any excipient
  • History of hypersensitivity to Vicineum or its components
  • Active infection with tuberculosis (clinical evaluation that includes clinical history, physical examination, and radiographic findings, and PPD testing if indicated), hepatitis B (known positive HBV surface antigen (HBsAg) result, hepatitis C, or human immunodeficiency virus (positive HIV 1/2 antibodies). Patients with HIV are excluded from participating on this clinical trial because their immunodeficiency would confound the evaluation of adverse events which would hinder meeting the primary objective. Subjects with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody [anti-HBc] and absence of HBsAg) are eligible. Subjects positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA.
  • History of leptomeningeal carcinomatosis
  • Receipt of live attenuated vaccination within 30 days prior to the first dose of Vicineum or durvalumab
  • Any condition that, in the opinion of the investigator, would interfere with evaluation of study treatment or interpretation of patient safety or study results
  • Subjects with uncontrolled seizures
  • Any unresolved toxicity NCI CTCAE Grade >=2 from previous anticancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria
  • Subjects with Grade >=2 neuropathy will be evaluated on a case-by-case basis after consultation with the Principal Investigator.
  • Subjects with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab may be included only after consultation with the Principal Investigator.

View trial on ClinicalTrials.gov


{{footer-clinical-trials-navigation}}
{{header-clinical-trials-navigation}}

PhAse 1/2 StuDy of Modern ImmunotherApy in BCG-RelaPsing UroThelial Carcinoma of the BLADDER - (ADAPT-BLADDER) HCRN GU16-243


Condition: Urothelial Carcinoma, Bladder Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03317158

Sponsor: Noah Hahn, M.D.

Phase: Phase 1/Phase 2

Eligibility:

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

Inclusion Criteria:

  • (All Patients): Subject must meet all of the following applicable criteria to participate in this study:
  • Histologically confirmed non-muscle invasive urothelial carcinoma of the bladder (Ta, T1, or Tis stage) on TURBT obtained within 42 days of registration.
  • ECOG (WHO) performance status 0 or 1
  • Age ≥ 18 years old at time of consent
  • Adequate hematologic, hepatic, and renal function as defined by the following laboratory parameters:
  • White blood cell count (WBC) > 3.0 K/mm^3
  • Absolute neutrophil count (ANC) ≥ 1.5 K/mm^3
  • Platelets ≥ 100 K/mm^3
  • Hemoglobin (Hgb) ≥ 9 g/dL
  • Serum total bilirubin: ≤ 1.5 x ULN
  • ALT and AST ≤ 2.5 x ULN
  • Serum creatinine clearance (CrCl) ≥ 30 mL/min using the Cockcroft-Gault equation, see formula below:
  • CrCl = [140-age (years)] x weight (kg) / [72 x serum Cr (mg/dL)] (if subject is female multiply the above by 0.85)
  • Subjects who give a written informed consent obtained according to local guidelines. Inclusion Criteria (Phase 1 Only):
  • In addition to the inclusion criteria required of all patients listed above, the following inclusion criteria are also required of patients enrolling to Phase 1 of the study.
  • BCG-unresponsive disease defined by any of the following:
  • Persistent or recurrent CIS with or without the presence of concurrent Ta or T1 tumors within 12 months of completion of adequate BCG therapy
  • Recurrent high-grade Ta or T1 tumors within 6 months of completion of adequate BCG therapy NOTE: In recognition of the fact that procedure scheduling factors beyond the control of the patient or treating physician may cause unintended delays in disease evaluations, patients with pure papillary tumors (Ta or T1) with no components of CIS with recurrence documented within 9 months of completion of adequate BCG therapy who meet all other

Eligibility Criteria:

  • may be considered for enrollment after consultation with the study chair.
  • Persistent T1 high-grade tumors at the first disease evaluation (e.g. 3- month post-treatment evaluation) following an adequate BCG induction course
  • Prostatic urethra involvement of NMIBC Adequate BCG therapy is defined as at least one of the following:
  • At least 5 of 6 doses of an initial induction BCG course plus at least 2 of 3 doses of maintenance therapy
  • At least 5 of 6 doses of an initial induction BCG course plus at least 2 of 6 doses of a second induction course NOTE: Patients with concurrent non-muscle invasive tumors (CIS, Ta, T1) in the prostatic urethra and/or concurrent non-invasive tumors (CIS, Ta) in the upper urinary tracts (ureter, renal pelvis) are permitted to enroll in Phase 1 of the study. Patients with concurrent T1 tumors in the upper urinary tracts (ureter, renal pelvis) are not eligible to enroll in Phase 1 of the study. Patients who have met the BCG-unresponsive criteria at any time point in their treatment history are permitted to enroll in Phase 1 of the study regardless of the time frame between their most recent BCG treatment administration and study registration dates. Inclusion Criteria (Phase 2 Only):
  • In addition to the inclusion criteria required of all patients listed above, the following inclusion criteria are also required of patients enrolling to Phase 2 of the study. Intermediate or high-risk NMIBC defined according to modified EORTC risk criteria summarized as follows:
  • Low-risk Tumors Initial or recurrent tumor > 12 months after resection with all of the following:
  • Solitary tumor
  • Low-grade
  • < 3 cm
  • No CIS
  • Intermediate-Risk Tumors: All tumors not defined in the two adjacent categories (between the category of low- and high-risk).
  • High-risk Tumors: Any of the following:
  • T1 tumor
  • High-grade
  • CIS
  • Multiple and recurrent and large (> 3 cm) Ta low-grade tumors (all conditions must be met for this point on Ta low-grade tumors).
  • Documented recurrence within 15 months of last exposure to intravesical therapy.
  • Recurrence after 1 prior induction course of intravesical BCG. 8. BCG-relapsing NMIBC defined as recurrent intermediate- or high-risk NMIBC after achievement of a complete response to initial BCG induction therapy which does not meet any of the BCG-unresponsive criteria outlined in section 3.1.2. OR BCG-persistent NMIBC defined as persistent intermediate- or high-risk NMIBC at the first disease evaluation after initial BCG induction therapy (with no intervening achievement of complete response) for which a second course of BCG induction therapy is considered a standard of care (e.g. CIS or high grade Ta tumors) which does not meet any of the BCG-unresponsive criteria outlined in section 3.1.2. NOTE: Patients who have received additional non-BCG based intravesical therapies (e.g. chemotherapy, non-BCG investigational agents) are eligible provided they have received only 1 prior course of BCG induction therapy and satisfy the above BCG-relapsing or BCG-persistent definitions. Inclusion Criteria (Phase 2 Patients with Persistent or Relapsed NMIBC who Cross-Over to Durvalumab Only):
  • In addition to the inclusion criteria described of all patients listed above, the following inclusion criteria are also required of patients originally enrolled in Phase 2 of the study who are noted to have NMIBC in follow up and opt to cross-over to durvalumab monotherapy.
  • Subjects with BCG-unresponsive disease defined by any of the following:
  • Prior treatment with 2 or more adequate courses of BCG (at least 5 of 6 induction installations and at least 2 of 3 maintenance installations for subjects on maintenance therapy).
  • Persistent T1 high-grade disease at the initial 3-month cystoscopy/TURBT assessment in subjects who received 5 of 6 inductions BCG installations.
  • Relapsed NMIBC within 6 months of last exposure to BCG
  • Prostatic urethra involvement of NMIBC Primary Exclusion Criteria: Exclusion Criteria (All Patients):
  • Subjects with muscle-invasive (i.e. T2, T3, T4), locally advanced unresectable, or metastatic urothelial carcinoma as assessed on baseline radiographic imaging obtained within 28 days prior to study registration. The required radiographic imaging includes:
  • Abdomen/Pelvis
  • CT scan
  • Chest
  • chest x-ray or CT scan
  • Subjects with another active second malignancy other than non-melanoma skin cancers and biochemical relapsed prostate cancer. Subjects that have completed all necessary therapy and are considered to be at less than 30% risk of relapse are not considered to have an active second malignancy and are eligible for enrollment.
  • Subjects who have received the last administration of an anti-cancer therapy including chemotherapy, immunotherapy, and monoclonal antibodies ≤ 4 weeks prior to starting study drug, or who have not recovered from the side effects of such therapy.
  • Any unresolved toxicity NCI CTCAE Grade ≥ 2 from previous anticancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria:
  • Patients with Grade ≥ 2 neuropathy will be evaluated on a case-by-case basis after consultation with the sponsor-investigator.
  • Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab may be included only after consultation with the sponsor-investigator.
  • Subjects who have received prior therapy with PD-1 or PD-L1 directed agents.
  • Subjects who have had any prior radiation to the prostate or pelvis.
  • Subjects who have undergone major surgery (e.g. intra-thoracic, intra-abdominal or intra-pelvic), open biopsy or significant traumatic injury ≤ 4 weeks prior to starting study drug, or subjects who have had minor procedures (i.e. TURBT), percutaneous biopsies or placement of vascular access device ≤ 1 week prior to starting study drug, or who have not recovered from side effects of such procedure or injury.
  • Subjects with any of the following concurrent severe and/or uncontrolled medical conditions which could compromise participation in the study:
  • Clinically significant cardiac diseases, including any of the following:
  • History or presence of serious uncontrolled ventricular arrhythmias.
  • Clinically significant resting bradycardia.
  • Any of the following within 3 months prior to starting study drug: myocardial infarction (MI), severe/unstable angina, Coronary Artery Bypass Graft (CABG), Congestive Heart Failure (CHF), Cerebrovascular Accident (CVA), Transient Ischemic Attack (TIA), Pulmonary Embolism (PE).
  • Uncontrolled hypertension defined by a SBP ≥ 160 mm Hg and/or DBP ≥ 100 mm Hg, with or without anti-hypertensive medication(s).
  • Cirrhosis
  • Active Infection (includes chronic active and chronic persistent).
  • Tuberculosis
  • Hepatitis B (known positive HBV surface antigen (HbsAg). Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody [anti-HBc] and absence of HbsAg) are eligible.
  • Hepatitis C. Patients positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA.
  • Known diagnosis of human immunodeficiency virus (HIV/positive HIV 1/2 antibodies) infection (HIV testing is not mandatory).
  • Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [e.g., colitis or Crohn's disease], diverticulitis [with the exception of diverticulosis], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome [granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc.]). The following are exceptions to this criterion:
  • Patients with vitiligo or alopecia.
  • Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement.
  • Any chronic skin condition that does not require systemic therapy.
  • Patients without active disease in the last 5 years may be included but only after consultation with the study physician.
  • Patients with celiac disease controlled by diet alone.
  • Other concurrent severe and/or uncontrolled concomitant medical conditions (e.g. active or uncontrolled infection, uncontrolled diabetes) that could cause unacceptable safety risks or compromise compliance with the protocol.
  • Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab. The following are exceptions to this criterion:
  • Intranasal, inhaled, 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.
  • Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication).
  • Usage of non-steroidal anti-inflammatory medications (NSAIDS) for the treatment of osteoarthritis and uric acid synthesis inhibitors for the treatment of gout are permitted.
  • Pregnant or breast-feeding women. Women of child-bearing potential must have a negative urine or serum test ≤ 14 days prior to starting study drug.
  • Women of child-bearing potential, who are biologically able to conceive, and not employing two forms of highly effective contraception or abstinence. Highly effective contraception or abstinence must be used from the time of informed consent, throughout the trial and up to 180 days after the last dose of durvalumab (e.g. male condom with spermicidal; diaphragm with spermicide; intra-uterine device). Women of child-bearing potential are defined as sexually mature women who have not undergone a hysterectomy or who have not been naturally postmenopausal for at least 12 consecutive months (i.e., who has had menses any time in the preceding 12 consecutive months). Women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause. The following age-specific requirements apply:
  • Women <50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution or underwent surgical sterilization (bilateral oophorectomy or hysterectomy).
  • Women ≥50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced menopause with last menses >1 year ago, had chemotherapy-induced menopause with last menses >1 year ago, or underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or hysterectomy).
  • Fertile males not willing to use contraception or abstinence, as stated above. Contraception or abstinence must be followed from screening through 180 days after receipt of the final dose of durvalumab therapy.
  • Subjects unwilling or unable to comply with the protocol.
  • Receipt of live attenuated vaccine within 30 days prior to the first dose of IP.
  • Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients. Exclusion Criteria (Phase 1 Only):
  • In Phase 1 of the study, there are no additional exclusion criteria beyond those described of all patients in the section listed above. Exclusion Criteria (Phase 2 Only):
  • In addition to the exclusion criteria described of all patients listed above, the following exclusion criteria apply to patients enrolling to Phase 2 of the study.
  • Subjects with BCG-unresponsive disease defined by any of the following:
  • Prior treatment with 2 or more adequate courses of BCG (at least 5 of 6 induction installations and at least 2 of 3 maintenance installations for subjects on maintenance therapy).
  • Persistent T1 high-grade disease at the initial 3-month cystoscopy/TURBT assessment in subjects who received 5 of 6 inductions BCG installations.
  • Relapsed NMIBC within 6 months of last exposure to BCG.
  • Prostatic urethra involvement of NMIBC.
  • Subjects with concurrent upper urinary tract (i.e. ureter, renal pelvis) non-invasive urothelial carcinoma. Exclusion Criteria (Phase 2 Patients with Persistent or Relapsed NMIBC who Cross-Over to Durvalumab Only):
  • In addition to the exclusion criteria described of all patients listed above, the following

Exclusion Criteria:

  • Exclusion Criteria (All Patients):
  • Subjects with muscle-invasive (i.e. T2, T3, T4), locally advanced unresectable, or metastatic urothelial carcinoma as assessed on baseline radiographic imaging obtained within 28 days prior to study registration. The required radiographic imaging includes:
  • Abdomen/Pelvis
  • CT scan
  • Chest
  • chest x-ray or CT scan
  • Subjects with another active second malignancy other than non-melanoma skin cancers and biochemical relapsed prostate cancer. Subjects that have completed all necessary therapy and are considered to be at less than 30% risk of relapse are not considered to have an active second malignancy and are eligible for enrollment.
  • Subjects who have received the last administration of an anti-cancer therapy including chemotherapy, immunotherapy, and monoclonal antibodies ≤ 4 weeks prior to starting study drug, or who have not recovered from the side effects of such therapy.
  • Any unresolved toxicity NCI CTCAE Grade ≥ 2 from previous anticancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria:
  • Patients with Grade ≥ 2 neuropathy will be evaluated on a case-by-case basis after consultation with the sponsor-investigator.
  • Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab may be included only after consultation with the sponsor-investigator.
  • Subjects who have received prior therapy with PD-1 or PD-L1 directed agents.
  • Subjects who have had any prior radiation to the prostate or pelvis.
  • Subjects who have undergone major surgery (e.g. intra-thoracic, intra-abdominal or intra-pelvic), open biopsy or significant traumatic injury ≤ 4 weeks prior to starting study drug, or subjects who have had minor procedures (i.e. TURBT), percutaneous biopsies or placement of vascular access device ≤ 1 week prior to starting study drug, or who have not recovered from side effects of such procedure or injury.
  • Subjects with any of the following concurrent severe and/or uncontrolled medical conditions which could compromise participation in the study:
  • Clinically significant cardiac diseases, including any of the following:
  • History or presence of serious uncontrolled ventricular arrhythmias.
  • Clinically significant resting bradycardia.
  • Any of the following within 3 months prior to starting study drug: myocardial infarction (MI), severe/unstable angina, Coronary Artery Bypass Graft (CABG), Congestive Heart Failure (CHF), Cerebrovascular Accident (CVA), Transient Ischemic Attack (TIA), Pulmonary Embolism (PE).
  • Uncontrolled hypertension defined by a SBP ≥ 160 mm Hg and/or DBP ≥ 100 mm Hg, with or without anti-hypertensive medication(s).
  • Cirrhosis
  • Active Infection (includes chronic active and chronic persistent).
  • Tuberculosis
  • Hepatitis B (known positive HBV surface antigen (HbsAg). Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody [anti-HBc] and absence of HbsAg) are eligible.
  • Hepatitis C. Patients positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA.
  • Known diagnosis of human immunodeficiency virus (HIV/positive HIV 1/2 antibodies) infection (HIV testing is not mandatory).
  • Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [e.g., colitis or Crohn's disease], diverticulitis [with the exception of diverticulosis], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome [granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc.]). The following are exceptions to this criterion:
  • Patients with vitiligo or alopecia.
  • Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement.
  • Any chronic skin condition that does not require systemic therapy.
  • Patients without active disease in the last 5 years may be included but only after consultation with the study physician.
  • Patients with celiac disease controlled by diet alone.
  • Other concurrent severe and/or uncontrolled concomitant medical conditions (e.g. active or uncontrolled infection, uncontrolled diabetes) that could cause unacceptable safety risks or compromise compliance with the protocol.
  • Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab. The following are exceptions to this criterion:
  • Intranasal, inhaled, 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.
  • Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication).
  • Usage of non-steroidal anti-inflammatory medications (NSAIDS) for the treatment of osteoarthritis and uric acid synthesis inhibitors for the treatment of gout are permitted.
  • Pregnant or breast-feeding women. Women of child-bearing potential must have a negative urine or serum test ≤ 14 days prior to starting study drug.
  • Women of child-bearing potential, who are biologically able to conceive, and not employing two forms of highly effective contraception or abstinence. Highly effective contraception or abstinence must be used from the time of informed consent, throughout the trial and up to 180 days after the last dose of durvalumab (e.g. male condom with spermicidal; diaphragm with spermicide; intra-uterine device). Women of child-bearing potential are defined as sexually mature women who have not undergone a hysterectomy or who have not been naturally postmenopausal for at least 12 consecutive months (i.e., who has had menses any time in the preceding 12 consecutive months). Women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause. The following age-specific requirements apply:
  • Women <50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution or underwent surgical sterilization (bilateral oophorectomy or hysterectomy).
  • Women ≥50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced menopause with last menses >1 year ago, had chemotherapy-induced menopause with last menses >1 year ago, or underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or hysterectomy).
  • Fertile males not willing to use contraception or abstinence, as stated above. Contraception or abstinence must be followed from screening through 180 days after receipt of the final dose of durvalumab therapy.
  • Subjects unwilling or unable to comply with the protocol.
  • Receipt of live attenuated vaccine within 30 days prior to the first dose of IP.
  • Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients. Exclusion Criteria (Phase 1 Only):
  • In Phase 1 of the study, there are no additional exclusion criteria beyond those described of all patients in the section listed above. Exclusion Criteria (Phase 2 Only):
  • In addition to the exclusion criteria described of all patients listed above, the following exclusion criteria apply to patients enrolling to Phase 2 of the study.
  • Subjects with BCG-unresponsive disease defined by any of the following:
  • Prior treatment with 2 or more adequate courses of BCG (at least 5 of 6 induction installations and at least 2 of 3 maintenance installations for subjects on maintenance therapy).
  • Persistent T1 high-grade disease at the initial 3-month cystoscopy/TURBT assessment in subjects who received 5 of 6 inductions BCG installations.
  • Relapsed NMIBC within 6 months of last exposure to BCG.
  • Prostatic urethra involvement of NMIBC.
  • Subjects with concurrent upper urinary tract (i.e. ureter, renal pelvis) non-invasive urothelial carcinoma. Exclusion Criteria (Phase 2 Patients with Persistent or Relapsed NMIBC who Cross-Over to Durvalumab Only):
  • In addition to the exclusion criteria described of all patients listed above, the following exclusion criteria apply to patients enrolling to the cross-over to durvalumab portion of the Phase 2 study.
  • Subjects with concurrent upper urinary tract (i.e. ureter, renal pelvis) non-invasive urothelial carcinoma.

View trial on ClinicalTrials.gov


{{footer-clinical-trials-navigation}}
{{header-clinical-trials-navigation}}

Phase II Trial of Neutron Radiotherapy With Concurrent Checkpoint Inhibitor Immunotherapy (Pembrolizumab) in Patients With Advanced Urothelial Carcinoma


Condition: Urothelial Carcinoma

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03486197

Sponsor: University of Washington

Phase: Phase 2

Eligibility:

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

Inclusion Criteria:

  • Pathologically proven (either histologic or cytologic) diagnosis of urothelial carcinoma
  • At least two sites of disease that are measurable by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria
  • Eligible for checkpoint inhibitor immunotherapy (pembrolizumab) per standard of care
  • No history of autoimmune disease requiring systemic therapy (e.g. steroids or biologic agents)
  • Absolute neutrophil count (ANC) ≥ 1500 /mcL
  • Platelets ≥ 100,000/mcL
  • Hemoglobin > 9 g/dL
  • Creatinine ≤ 1.5 x upper limit of normal (ULN) OR ≥ 60 mL/min
  • Total bilirubin ≤ 1.5 ULN OR direct bilirubin ≤ ULN if total bilirubin > 1.5 x ULN
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN OR < 5 x ULN if patient has liver metastasis
  • Albumin >= 2.5 g/dL
  • International normalized ratio (INR) or PT ≤ 1.5 x ULN unless on anticoagulation therapy, in which case prothrombin time (PT) or partial thromboplastin time (PTT) should be in the therapeutic range
  • PTT ≤ 1.5 x ULN unless on anticoagulation therapy, in which case PT or PTT should be in the therapeutic range
  • Eligible for neutron radiation treatment to 1-3 sites of metastatic disease (lesions do not have to be symptomatic)
  • No steroids for at least 2 weeks prior to enrollment, and patient must not be expected to require steroids during the study period
  • Zubrod performance status 0-2
  • Patient must sign study specific informed consent prior to study entry
  • Patients who are sexually active must use medically acceptable forms of contraception
  • Life expectancy must be > 3 months

Exclusion Criteria:

  • Has a known history of active TB (Bacillus tuberculosis)
  • Hypersensitivity to pembrolizumab or any of its excipients
  • Has a known additional malignancy that is progressing or requires active treatment
  • Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent
  • Has a known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies)
  • Has known active hepatitis B (e.g., hepatitis B virus surface antigen [HBsAg] reactive) or hepatitis C (e.g., hepatitis C virus [HCV] ribonucleic acid [RNA] [qualitative] is detected)
  • Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
  • Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator
  • Has known history of, or any evidence of active, non-infectious pneumonitis
  • Has an active infection requiring systemic therapy
  • Has received a live vaccine within 30 days of planned start of study therapy
  • Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis; subjects with previously treated brain metastases may participate provided there is 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

View trial on ClinicalTrials.gov


{{footer-clinical-trials-navigation}}
{{header-clinical-trials-navigation}}

A Study of Enfortumab Vedotin (ASG-22CE) as Monotherapy or in Combination With Other Anticancer Therapies for the Treatment of Urothelial Cancer


Condition: Carcinoma, Transitional Cell, Urinary Bladder Neoplasms, Urologic Neoplasms, Renal Pelvis Neoplasms, Urothelial Cancer, Ureteral Neoplasms, Urethral Neoplasms

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03288545

Sponsor: Astellas Pharma Global Development, Inc.

Phase: Phase 1/Phase 2

Eligibility:

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

Inclusion Criteria:

  • Locally advanced or metastatic urothelial cancer (la/mUC)
  • Cohorts A, B, D, E, F, G and K.
  • Histologically documented la/mUC, including squamous differentiation or mixed cell types.
  • An Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0, 1 or 2: Participants with ECOG performance status of 2 must meet the following additional criteria: hemoglobin ≥10 g/dL, GFR ≥50 mL/min, may not have NYHA Class III heart failure.
  • Eligible for pembrolizumab (Dose-escalation cohorts, Cohorts A, B, G and K Combination Arm).
  • Dose-escalation cohorts: Ineligible for first-line cisplatin-based chemotherapy and no prior treatment for la/mUC, or have disease progression following at least 1 platinum-containing treatment.
  • Cohort A: Ineligible for cisplatin-based chemotherapy and no prior treatment for la/mUC. No prior adjuvant/neoadjuvant platinum-based therapy in at least 12 months.
  • Cohort B: Must have disease progression during/following treatment with at least 1 platinum-containing regimen for la/mUC or disease recurrence.
  • Cohort D: Eligible for cisplatin-based chemotherapy and no prior treatment for la/mUC. No prior adjuvant/neoadjuvant platinum-based therapy in at least 12 months.
  • Cohort E: Ineligible for cisplatin-based chemotherapy, eligible for carboplatin, and no prior treatment for la/mUC. No prior adjuvant/neoadjuvant platinum-based therapy in at least 12 months.
  • Cohort F: Ineligible for platinum-based chemotherapy, or disease progression during/following at least 1 prior treatment for la/mUC. Eligible for gemcitabine.
  • Cohort G: Eligible for platinum-based chemotherapy (either cisplatin or carboplatin) and no prior treatment for la/mUC. No prior adjuvant/neoadjuvant platinum-based therapy in at least 12 months.
  • Cohort K: Ineligible for cisplatin-based chemotherapy due to at least 1 of the following: Glomerular filtration rate (GFR) <60 mL/min and ≥30 mL/min, ECOG performance status of 2, NCI CTCAE Version 4.03 Grade ≥2 hearing loss, New York Heart Association (NYHA) Class III heart failure. No prior systemic treatment for locally advanced or metastatic disease. No adjuvant/neoadjuvant platinum-based therapy within 12 months prior to randomization.
  • Muscle Invasive Bladder Cancer (MIBC)- Cohorts H, J and L.
  • Histologically confirmed MIBC with predominant >50% urothelial histology: Cohorts H and J: Clinical stage cT2-T4aN0M0; Cohort L: Clinical stage cT2-T4aN0M0 or cT1-T4aN1M0: Participants with pT1 disease are eligible only if they have N1 disease on imaging. Mixed cell types are eligible if urothelial cancer is predominant (>50%); Participants with plasmacytoid and/or neuroendocrine tumors are ineligible regardless of component percentage. Urothelial tumors not originating in the bladder (eg, upper tract tumors, urethral tumors) are ineligible.
  • Must be cisplatin-ineligible.
  • Cohort-specific eligibility: Cohort J, H, and L: No prior systemic treatment, chemoradiation, or radiation therapy for MIBC. May have received prior intravesical Bacillus Calmette-Guerin (BCG) or intravesical chemotherapy for non-MIBC; Cohort J: Eligible for pembrolizumab.
  • ECOG performance status of 0, 1, or 2.
  • Anticipated life expectancy of ≥3 months.
  • Tumor samples with an associated pathology report from the diagnostic transurethral resection of a bladder tumor done 90 days prior to the first dose of study treatment must be available prior to enrollment and determined to be sufficient for pathology review and biomarker analysis.
  • Participants must be deemed eligible for RC+PLND.

Exclusion Criteria:

  • la/mUC
  • Cohorts A, B, D, E, F, G, and K
  • Received any prior treatment with a PD-1 inhibitor, PD-L1 inhibitor, or PD-L2 inhibitor, except Cohort F.
  • Received any prior treatment with stimulatory or co-inhibitory T-cell receptor agents, such as CD137 agonists, OX-40 agonists, or cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitors (except Cohort F).
  • Ongoing sensory or motor neuropathy Grade 2 or higher.
  • Active central nervous system (CNS) metastases.
  • Ongoing clinically significant toxicity (Grade 2 or greater) associated with prior treatment (including radiotherapy or surgery).
  • Conditions requiring high doses of steroids or other immunosuppressive medications.
  • Prior treatment with enfortumab vedotin or other monomethyl auristatin E (MMAE)-based antibody-drug conjugates (ADCs).
  • Uncontrolled diabetes mellitus.
  • MIBC
  • Cohorts H, J, and L
  • Received prior systemic treatment, chemoradiation, and/or radiation therapy of muscle invasive bladder cancer.
  • Received any prior treatment with a CPI.
  • Received any prior treatment with stimulatory or co-inhibitory T-cell receptor agents, such as CD137 agonists, CTLA-4 inhibitors, or OX-40 agonists.
  • For participants in Cohort H, evidence of nodal disease on imaging. For participants in Cohort L, ≥N2 nodal disease on imaging.
  • Participant has undergone partial cystectomy of the bladder to remove any NMIBC or MIBC.
  • Ongoing sensory or motor neuropathy Grade 2 or higher.
  • Conditions requiring high doses of steroids or other immunosuppressive medications.
  • Prior treatment with enfortumab vedotin or other MMAE-based ADCs for urothelial cancer.
  • Participants with a history of another invasive malignancy within 3 years before first dose of study drug.

View trial on ClinicalTrials.gov


{{footer-clinical-trials-navigation}}
{{header-clinical-trials-navigation}}

A Phase 3, Open-label, Randomized Study of Nivolumab Combined With Ipilimumab, or With Standard of Care Chemotherapy, Versus Standard of Care Chemotherapy in Participants With Previously Untreated Unresectable or Metastatic Urothelial Cancer


Condition: Urothelial Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03036098

Sponsor: Bristol-Myers Squibb

Phase: Phase 3

Eligibility:

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

Inclusion Criteria:

  • Histological or cytological evidence of metastatic or surgically inoperable transitional cell cancer (TCC) of the urothelium involving the renal pelvis, ureter, bladder or urethra
  • No prior systemic chemotherapy for metastatic or surgically inoperable urothelial cancer (UC)
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1
  • Women and men must agree to follow specific methods of contraception, if applicable Exclusion Criteria:
  • Disease that is suitable for local therapy administered with curative intent
  • Any serious or uncontrolled medical disorder in the opinion of the investigator that may increase the risk associated with study participation or study drug administration or interfere with the interpretation of study results
  • Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways Other protocol-defined inclusion/

Exclusion Criteria:

  • Disease that is suitable for local therapy administered with curative intent
  • Any serious or uncontrolled medical disorder in the opinion of the investigator that may increase the risk associated with study participation or study drug administration or interfere with the interpretation of study results
  • Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways Other protocol-defined inclusion/exclusion criteria apply

View trial on ClinicalTrials.gov


{{footer-clinical-trials-navigation}}
{{header-clinical-trials-navigation}}

Randomized Phase II Study of Neoadjuvant Nivolumab With and Without Urelumab in Cisplatin-Ineligible or Chemotherapy-refusing Patients With Muscle-Invasive Urothelial Carcinoma of the Bladder


Condition: Urothelial Carcinoma, Bladder Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT02845323

Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Phase: Phase 2

Eligibility:

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

Inclusion Criteria:

  • Electively refusing cisplatin-based neoadjuvant chemotherapy or
  • Ineligible to receive cisplatin-based neoadjuvant chemotherapy based upon at least one of the following criteria:
  • Creatinine clearance < 60 ml/min
  • ECOG status =2
  • Grade > 2 hearing loss
  • Grade > 2 neuropathy
  • New York Heart Association Class III heart failure
  • Age ≥ 18 years old at time of consent
  • Patients must have the following laboratory values: a) Absolute neutrophil count (ANC) ≥ 1.5 K/mm3 (must be stable off any growth factor within 4 weeks of first study drug administration) b) Platelets ≥ 100 K/mm3 (transfusion to achieve this level is not permitted within 2 weeks of first study drug administration) c) Hemoglobin (Hgb) ≥ 9 g/dL d) Serum total bilirubin: ≤ 1.5 x ULN e) ALT and AST ≤ 3.0 x ULN f) Serum creatinine clearance (CrCl) ≥ 30 mL/min using the Cockcroft-Gault equation, see formula below:
  • CrCl = [140-age (years)] x weight (kg) / [72 x serum Cr (mg/dL)] (if patient is female multiply the above by 0.85)
  • Patients who give a written informed consent obtained according to local guidelines

Exclusion Criteria:

  • Patients with locally advanced unresectable or metastatic urothelial carcinoma as assessed on baseline radiographic imaging obtained within 28 days prior to study registration. The required radiographic imaging includes: a) Abdomen/Pelvis
  • CT scan b) Chest
  • chest x-ray or CT scan
  • Patients with concurrent upper urinary tract (i.e. ureter, renal pelvis) invasive urothelial carcinoma.
  • Patients with another active second malignancy other than non-melanoma skin cancers and biochemical relapsed prostate cancer
  • Patients who have received the last administration of an anti-cancer therapy including chemotherapy, immunotherapy, and monoclonal antibodies ≤ 4 weeks prior to starting study drug, or who have not recovered from the side effects of such therapy
  • Patients who have received prior therapy with immune checkpoint inhibitors (e.g. anti-PD-1, anti-PD-L1, anti-LAG3, anti-CTLA-4) or immune costimulatory molecules (e.g. anti-CD137, anti-OX40, anti-GITR) directed agents.
  • Patients who have had radiotherapy ≤ 4 weeks prior to starting study drug, or who have not recovered from radiotherapy toxicities
  • Patients who have undergone major surgery (e.g. intra-thoracic, intra-abdominal or intra-pelvic), open biopsy or significant traumatic injury ≤ 4 weeks prior to starting study drug, or patients who have had minor procedures (i.e. TURBT), percutaneous biopsies or placement of vascular access device ≤ 1 week prior to starting study drug, or who have not recovered from side effects of such procedure or injury
  • Patients with history of alcoholic or non-alcoholic steatohepatitis (NASH), auto-immune hepatitis, or previous grade 3-4 drug-related hepatitis. (Note: Patients with radiographic evidence of steatohepatitis are excluded unless a liver biopsy is obtained demonstrating no evidence of alcoholic or non-alcoholic steatohepatitis).
  • Patient with history of prior solid organ or allogeneic bone marrow transplant.
  • Patients with any of the following concurrent severe and/or uncontrolled medical conditions which could compromise participation in the study: 1. Clinically significant cardiac diseases, including any of the following: i. History or presence of serious uncontrolled ventricular arrhythmias ii.Clinically significant resting bradycardia iii.Any of the following within 3 months prior to starting study drug: myocardial infarction (MI), severe/unstable angina, Coronary Artery Bypass Graft (CABG), Congestive Heart Failure (CHF), Cerebrovascular Accident (CVA), Transient Ischemic Attack (TIA), Pulmonary Embolism (PE) iv.Uncontrolled hypertension defined by a SBP ≥ 160 mm Hg and/or DBP ≥ 100 mm Hg, with or without anti-hypertensive medication(s) b) Cirrhosis, chronic active hepatitis or chronic persistent hepatitis c) Known diagnosis of human immunodeficiency virus (HIV) infection (HIV testing is not mandatory) d) Known diagnosis of any condition (i.e. post-hematopoietic or organ transplant, rheumatoid arthritis, systemic lupus erythematosus, inflammatory bowel disease, etc.) that requires chronic immunosuppressive therapy. Usage of non-steroidal anti-inflammatory medications (NSAIDS) for the treatment of osteoarthritis and uric acid synthesis inhibitors for the treatment of gout are permitted. For questions, please consult the study chair. e) Other concurrent severe and/or uncontrolled concomitant medical conditions (e.g. active or uncontrolled infection, uncontrolled diabetes) that could cause unacceptable safety risks or compromise compliance with the protocol
  • Pregnant or breast-feeding women
  • Women of child-bearing potential, who are biologically able to conceive, and not employing two forms of highly effective contraception. Highly effective contraception must be used throughout the trial and up to 8 weeks after the last dose of study drug (e.g. male condom with spermicidal; diaphragm with spermicide; intra-uterine device). Women of child-bearing potential, defined as sexually mature women who have not undergone a hysterectomy or who have not been naturally postmenopausal for at least 12 consecutive months (i.e., who has had menses any time in the preceding 12 consecutive months), must have a negative serum pregnancy test ≤ 14 days prior to starting study drug
  • Fertile males not willing to use contraception, as stated above
  • Patients unwilling or unable to comply with the protocol

View trial on ClinicalTrials.gov


{{footer-clinical-trials-navigation}}
{{header-clinical-trials-navigation}}

A Phase 2, Two-arm Multicenter, Open-Label Study to Determine the Efficacy and the Safety of Two Different Dose Regimens of a Pan-FGFR Tyrosine Kinase Inhibitor JNJ-42756493 in Subjects With Metastatic or Surgically Unresectable Urothelial Cancer With FGFR Genomic Alterations


Condition: Urothelial Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT02365597

Sponsor: Janssen Research & Development, LLC

Phase: Phase 2

Eligibility:

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

Inclusion Criteria:

  • Must have histologic demonstration of metastatic or surgically unresectable urothelial cancer. Minor components of variant histology such as glandular or squamous differentiation, or evolution to more aggressive phenotypes such as sarcomatoid or micropapillary change are acceptable
  • Must have measurable disease according to the Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1) at baseline
  • Must have an Eastern Cooperative Oncology Group (ECOG) performance status score 0, 1, or 2
  • Must have adequate bone marrow, liver, and renal function as described in protocol
  • Negative pregnancy test (urine or serum beta human chorionic gonadotropin [b-hCG]) at Screening for women of child bearing potential who are sexually active
  • Must have shown disease progression according to RECIST, version 1.1, following prior chemotherapy for metastatic or surgically unresectable urothelial cancer. Participants who received neoadjuvant or adjuvant chemotherapy and showed disease recurrence or progression according to RECIST, version 1.1, within 12 months of the last dose are considered to have received chemotherapy in the metastatic setting. These participants will be referred to as chemo-refractory participants. (Participants who have shown disease progression according to RECIST, version 1.1 following prior treatment with anti-Programmed death-ligand 1 (anti PDL1/PD1) antibodies are also eligible) For DDI substudy
  • Disease progression following prior chemotherapy for metastatic or surgically unresectable urothelial cancer. Participants who received neoadjuvant or adjuvant chemotherapy and showed disease recurrence or progression within 12 months of the last dose are considered to have received chemotherapy in the metastatic setting.

Exclusion Criteria:

  • Received chemotherapy, targeted therapies, definitive radiotherapy, or treatment with an investigational anticancer agent within 2 weeks (in the case of nitrosoureas and mitomycin C, within 6 weeks; in the case of immunotherapy, within 4 weeks) before the first administration of study drug. Localized palliative radiation therapy (but should not include radiation to target lesions) and ongoing bisphosphonates and denosumab, are permitted
  • Has persistent phosphate level greater than upper limit of normal (ULN) during screening (within 14 days of treatment and prior to Cycle 1 Day 1) and despite medical management
  • Has a history of or current uncontrolled cardiovascular disease
  • Females who are pregnant, breast-feeding, or planning to become pregnant within 3 months after the last dose of study drug and males who plan to father a child while enrolled in this study or within 5 months after the last dose of study drug
  • Has not recovered from reversible toxicity of prior anticancer therapy (except toxicities which are not clinically significant such as alopecia, skin discoloration, or Grade 1 neuropathy)

View trial on ClinicalTrials.gov


{{footer-clinical-trials-navigation}}
{{header-clinical-trials-navigation}}

A Phase II Trial of sEphB4-HSA in Combination With Anti PD1 Antibody Pembrolizumab (MK-3475) for Solid Tumors


Condition: Stage IV Bladder Urothelial Carcinoma, Prostate Cancer, Urothelial Carcinoma

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT02717156

Sponsor: University of Southern California

Phase: Phase 2

Eligibility:

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

Inclusion Criteria:

  • (for all Cohorts):
  • Be willing and able to provide written informed consent/assent for the trial
  • Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) performance scale
  • Absolute neutrophil count (ANC) >= 1,500/mcL
  • Platelets >= 100,000/mcL
  • Hemoglobin >= 9 g/dL or >= 5.6 mmol/L without transfusion or erythropoietin (EPO) dependency (within 7 days of assessment)
  • Measured or calculated creatinine clearance (glomerular filtration rate [GFR] can also be used in place of creatinine or creatinine clearance [CrCl]) >= 30mL/min for subject with creatinine levels > 1.5 X institutional upper limit of normal (ULN)
  • Serum total bilirubin =< 1.5 X ULN or direct bilirubin =< ULN for subjects with total bilirubin levels > 1.5 ULN
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 X ULN or =< 5 X ULN for subjects with liver metastases
  • Albumin >= 2.5 mg/dL
  • International normalized ratio (INR) or prothrombin time (PT) =< 1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or partial thromboplastin time (PTT) is within therapeutic range of intended use of anticoagulants
  • Activated partial thromboplastin time (aPTT) =< 1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants
  • Recovered to grade 1 from the effects (excluding alopecia) of any prior therapy for their malignancies
  • Female subject of childbearing potential should have a negative urine or serum pregnancy; 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 adequate method of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days 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 > 1 year
  • Male subjects must agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy Criteria specific to 2nd line and 3rd line and beyond cohorts (Cohorts A and B):
  • Advanced (metastatic or recurrent) pathologically proven urothelial carcinoma which is refractory to platinum based due to disease progression on a platinum containing regimen; patients progressing within 12 months of their last dose of platinum-based neoadjuvant or adjuvant chemotherapy will be considered platinum refractory
  • Have measurable disease based on RECIST 1.1
  • Be willing to provide tissue from a newly obtained core or excisional biopsy of a tumor lesion; newly-obtained is defined as a specimen obtained for up to 12 weeks (84 days) after discontinuation of previous systemic therapy and prior to initiation of treatment on day 1 on this study; subjects for whom newly-obtained samples cannot be provided (e.g. inaccessible or subject safety concern) may submit an archived specimen only upon agreement from the Sponsor; an optional core biopsy will be requested from an accessible metastatic site after 2 cycles of treatment and prior to progression of disease to help the investigators better understand the activity of these drugs in tumor tissue. Criteria specific to the neoadjuvant urothelial cohort (Cohort C):
  • Must have tumor stage ≥T2 AND ≤T4a, N0, M0 (AJCC 8th edition) urothelial carcinoma of the bladder deemed resectable and planned for radical cystectomy with curative intent. T4 due to infiltration of the prostate is allowed.
  • Must have TURBT specimen obtained within 12 weeks prior to the first day of treatment on the study and the specimen must include muscle. Subjects for whom a TURBT specimen within 12 weeks of C1D1 cannot be provided, but an older specimen is available (e.g. unlikely to be able to obtain adequate specimen or subject safety concern) may submit an archived specimen only upon written agreement from the Sponsor.
  • Prior intravesical therapy is allowed. However, patients who have received prior systemic therapy within 12 months enrollment are excluded. Criteria specific to the neoadjuvant prostate cohort (Cohort D):
  • Must have biopsy proven prostate cancer (Gleason Score ≥7, and PSA >4.0 ng/mL- rare cases can be reviewed and approved with a written agreement from the Sponsor) amenable to radical prostatectomy.
  • Must have appropriate staging imaging showing no evidence of distant metastatic disease. Choice of imaging is per treating physician- some acceptable imaging examples include MRI of pelvis, CT of abdomen and pelvis, bone scan, Axumin PET CT, and PSMA PET CT. For Cohort D, the imaging studies may be considered valid for enrollment beyond the 28 days at the discretion of the treating physician and no longer than 90 days.

Exclusion Criteria:

  • Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment
  • Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment
  • Has a known history of active TB (bacillus tuberculosis)
  • Hypersensitivity to pembrolizumab or any of its excipients
  • Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study day 1 or who has not recovered (ie, =< grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier
  • Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study day 1 or who has not recovered (ie, =< grade 1 or at baseline) from adverse events due to a previously administered agent; Note: subjects with =< grade 2 neuropathy are an exception to this criterion and may qualify for the study; Note: if subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy
  • Has a known additional malignancy that is progressing or requires active treatment; exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
  • 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 four 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
  • Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. 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, etc) is not considered a form of systemic treatment
  • Has known history of, or any evidence of active, non-infectious pneumonitis
  • Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
  • 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
  • Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent, or sEsphB4-HSA
  • Has a known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies)
  • Has known active Hepatitis B (eg, hepatitis B surface antigen [HBsAg] reactive) or Hepatitis C (eg, hepatitis C virus [HCV] ribonucleic acid [RNA] [qualitative] is detected)
  • Has New York Heart Association (NYHA) class 3 or 4, myocardial infarction, acute coronary syndrome, diabetes mellitus with ketoacidosis or chronic obstructive pulmonary disease (COPD) requiring hospitalization in the preceding 6 months; or any other intercurrent medical condition that contraindicates treatment with sEphB4HSA or pembrolizumab (MK-3475) or places the patient at undue risk for treatment related complications
  • Has received a live vaccine within 30 days of planned start of study therapy; Note: seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (eg, flu-mist) are live attenuated vaccines, and are not allowed
  • Uncontrolled hypertension is excluded- systolic blood pressure >140mmHg or diastolic >90mmHg. Patients experiencing white coat hypertension in the office, may be considered eligible if blood pressure log at home is within acceptable limits AND upon review and agreement from the Sponsor.

View trial on ClinicalTrials.gov


{{footer-clinical-trials-navigation}}
{{header-clinical-trials-navigation}}

An Open Label, Single-arm, Phase 2 Study of Neoadjuvant Pembrolizumab (MK-3475) Before Cystectomy for Patients With Muscle-invasive Urothelial Bladder Cancer.


Condition: Urothelial Bladder Carcinoma

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT02736266

Sponsor: Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

Phase: Phase 2

Eligibility:

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

Inclusion Criteria:

  1. Willing and able to provide written informed consent.
  2. Ability to comply with the protocol.
  3. Age ≥ 18 years.
  4. Histopathologically confirmed transitional cell carcinoma. Patients with mixed histologies are required to have a dominant (i.e. 50% at least) transitional cell pattern.
  5. Fit and planned for cystectomy (according to local guidelines).
  6. Clinical stage T2-T4a N0 M0 disease by CT (or MRI) + PET/CT (within 4 weeks of randomization by RECIST v1.1).
  7. Residual disease after TURB (surgical opinion, cystoscopy or radiological presence).
  8. Representative formalin-fixed paraffin-embedded (FFPE) tumor specimens (blocks preferred) or at least 15 unstained slides, with an associated pathology report, for testing at the study sponsor site and determined to be evaluable for tumor PD-L1 expression prior to study enrolment; patients with fewer than 15 unstained slides available at baseline (but no fewer than 10) may be eligible following discussion with Merck representatives.
  9. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or
  10. Adequate hematologic and end-organ function tests.

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.
  • Previously intravenous chemotherapy bladder cancer. Patients who have previously had radiotherapy or concurrent chemo-radiation would be eligible.
  • Malignancies other than UBC 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 measurable nodal or metastatic disease.
  • Evidence of significant uncontrolled concomitant disease that could affect compliance with the protocol or interpretation of results, including significant liver disease (such as cirrhosis, uncontrolled major seizure disorder, or superior vena cava syndrome).
  • 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.
  • Significant cardiovascular disease, such as New York Heart Association cardiac disease (Class II or greater), myocardial infarction within 3 months prior to enrolment, unstable arrhythmias, or unstable angina.
  • 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 enrolment or anticipation of need for a major surgical procedure during the course of the study other than for diagnosis.
  • History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
  • Known hypersensitivity or allergy to biopharmaceuticals produced in Chinese hamster ovary cells or any component of the pembrolizumab formulation
  • 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
  • Patients with prior allogeneic stem cell or solid organ transplantation.
  • History of idiopathic pulmonary fibrosis
  • Positive test for HIV.
  • Patients with active hepatitis infection
  • Patients with active tuberculosis.
  • Prior treatment with anti-programmed death-1 (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
  • History of severe immune-related adverse effects from anti-CTLA-4 (CTCAE Grade 3 and 4).
  • Treatment with systemic immunostimulatory agents within 4 weeks or five half-lives of the drug, whichever is shorter, prior to enrolment.

View trial on ClinicalTrials.gov


{{footer-clinical-trials-navigation}}
{{header-clinical-trials-navigation}}

A Phase II Open Label Single Arm Study of Adjuvant Nivolumab Following Chemo-Radiation in Localized Muscle-Invasive Bladder Cancer (NEXT)


Condition: Bladder Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03171025

Sponsor: University of Utah

Phase: Phase 2

Eligibility:

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

Inclusion Criteria:

  • Patients with muscularis propria invasion clinical stages 2 to 4 (T2-4b, N0 or N+, M0 or T1 with N+), who are not candidates for radical cystectomy.
  • Patients may have undergone partial cystectomy for removal of bladder tumor prior to chemoradiation. Patients who have M1 disease at any time prior to start of treatment are not eligible.
  • Staging is determined prior to chemoradiation
  • Patients have been evaluated by a urologic oncologist to determine eligibility for radical cystectomy prior to chemoradiation. Patients may not be candidates for radical cystectomy due to one or more reasons such as but not limited to comorbidities, age, surgical risk or patient refusal to undergo radical cystectomy. Patients who refuse to undergo radical cystectomy are not required to be evaluated by a urologic oncologist.
  • Patients must have histologically proven primary adenocarcinoma, transitional, squamous-cell, or sarcomatoid carcinoma primary of the bladder, urethra, or lower ureter.
  • Treating investigator has determined that the patients are not a candidate for radical cystectomy. Patients have been evaluated by a urologic oncologist to determine eligibility for radical cystectomy prior to chemoradiation. Patients may not be candidates for radical cystectomy due to one or more reasons such as, but not limited to, comorbidities, age, surgical risk, or patient refusal to undergo radical cystectomy.
  • Tumor tissue from the most recently resected site of disease (preferable) or from the transurethral resection that yielded the initial muscle invasive diagnosis must be provided for biomarker correlative analyses. Enrollment is permitted if adequate archived tissue is unavailable.
  • Patients must have received systemic radiosensitizing chemotherapy with definitive pelvic radiation therapy. Patients may have received partial amount of chemotherapy and radiation (both) to be eligible.
  • Platinum based chemotherapy prior to chemoradiation is permitted but not mandatory
  • Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤2
  • Age ≥18.
  • Adequate bone marrow function White Blood Cell (WBC) > 2000/µl, neutrophils >1500/µl, Hemoglobin >9.0 g/dl.
  • Serum bilirubin and aminotransferase values less than 1.5 times the upper limit of the normal range
  • Creatinine clearance of 20 ml/min or greater as measured by the Cockroft-Gault formula
  • Able to start study treatment within 90 days of completion of chemoradiation.
  • Female subject of childbearing potential should have a negative urine or serum pregnancy 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 should 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 5 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 > 1 year.
  • Male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 7 months after the last dose of study therapy.
  • All toxicities attributed to prior anti-cancer therapy other than nephropathy, neuropathy, hearing loss, alopecia and fatigue must have resolved to Grade 1 (NCI CTCAE version 4.03) or baseline before administration of study drug. Subjects with toxicities attributed to prior anti-cancer therapy which are not expected to resolve and result in long lasting sequelae, such as neuropathy after platinum based therapy, are permitted to enroll.
  • Able to provide informed consent and willing to sign an approved consent form that conforms to federal and institutional guidelines.

Exclusion Criteria:

  • Evidence of distant metastases or lymph node metastasis (es) that was not within the radiation field.
  • Known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin. A history of localized early stage malignancy that has undergone potentially curative therapy or is low grade and does not require active treatment is allowed.
  • Diffuse bladder carcinoma in situ (CIS) that was not able to be encompassed in a boost radiotherapy volume
  • Patients with inflammatory bowel disease
  • Patients with active, known or suspected autoimmune disease. 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.
  • Patients with a condition requiring systemic treatment with either corticosteroids (>10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 day of study drug administration. Inhaled, ocular, intraarticular, intranasal and topical steroids are permitted.
  • Patients with a known chronic immunocompromised state, HIV infection or active Hepatitis B or Hepatitis C infection.
  • Pregnancy or women of childbearing potential not willing to use contraception and men who are sexually active and not willing/able to use medically acceptable forms of contraception and breast-feeding women not willing to stop breastfeeding during study.
  • Severe active co-morbidity as determined by the investigator or principal investigator
  • Life expectancy less than 2 years

View trial on ClinicalTrials.gov


{{footer-clinical-trials-navigation}}
{{header-clinical-trials-navigation}}

A Phase I Trial for the Use of Intravesical Cabazitaxel, Gemcitabine, and Cisplatin (CGC) in the Treatment of BCG-Refractory Non-muscle Invasive Urothelial Carcinoma of the Bladder Cancer


Condition: Urothelial Carcinoma of the Urinary Bladder

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT02202772

Sponsor: James M. McKiernan

Phase: Phase 1/Phase 2

Eligibility:

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

Inclusion Criteria:

  • Patients must have a histologically confirmed diagnosis of non- muscle invasive urothelial carcinoma of the bladder at the study institution prior to the beginning of the study. This includes patients with:
  • High grade Ta papillary lesion(s)
  • High or low grade T1 papillary lesion(s)
  • Carcinoma In Situ (CIS), with or without Ta or T1 papillary tumor(s) of any grade The patient must have Bacillus Calmette-Guerin (BCG) refractory or recurrent non-muscle invasive bladder cancer
  • Refractory disease is defined as evidence of persistent high risk bladder cancer (high grade Ta, T1 and/or CIS) at the first cystoscopic exam after the initial 6 week induction course of BCG or at the 6 month cystoscopic exam.
  • Recurrent disease is defined as reappearance of disease after achieving a tumor- free status by 6 months following a full induction course of BCG with or without maintenance BCG. Participants must have recurred within 18 months following the last dose of BCG.
  • Low-grade superficial (Ta) disease will not be considered recurrent.
  • Patients must exhibit disease recurrence after receiving some form of standard intravesical therapy that must include a minimum of one induction course of BCG and may also include prior exposure to mitomycin, interferon, single agent gemcitabine or taxane therapy or maintenance.
  • Patients must be eligible for radical cystectomy and refuse this standard of care treatment or not be a surgical candidate for radical cystectomy based on other comorbidities.
  • All grossly visible disease in the bladder must be fully resected and pathologic stage will be confirmed at the study institution.
  • Patients enrolled in other clinical trials must have received their last treatment at least 6 weeks prior to enrollment.
  • Age > 18 and must be able to read, understand and sign informed consent
  • Patients must have an Eastern Cooperative Oncology Group (ECOG) performance Status: ECOG of 0 or 1 including patients who are not surgical candidates due to comorbid conditions.
  • Women of childbearing potential must have a negative pregnancy test.
  • All patients of childbearing potential must be willing to consent to using effective contraception, i.e., intrauterine device (IUD), Birth control pills, Depo-Provera, and condoms while on treatment and for 3 months after their participation in the study ends.
  • No experimental intravesical therapy within 6 weeks of study entry

Exclusion Criteria:

  • History of severe hypersensitivity reaction (≥grade 3) to docetaxel
  • History of severe hypersensitivity reaction (≥grade 3) to polysorbate 80 containing drugs
  • Concurrent or planned treatment with strong inhibitors or strong inducers of cytochrome P450 3A4/5 (a one week wash-out period is necessary for patients who are already on I these treatments)
  • Concurrent malignancy diagnosed within 6 months of entry to the study.
  • Concurrent treatment with any systemic chemotherapeutic agent.
  • Inadequate organ and bone marrow function as evidenced by:
  • Hemoglobin: less than 8.0 g/dL
  • Absolute neutrophil count: less than 1.5 x 10^9/L
  • Platelet count: less than 80x 10^9/L
  • Aspartate Aminotransferase Test (AST) / Serum Glutamic Oxaloacetic Transaminase (SGOT) and/or ( Alanine Aminotransferase Test (ALT)/ Serum Glutamic Pyruvic Transaminase (SGPT) >2.5 x upper limit of normal (ULN);
  • Total bilirubin >1.5 x ULN
  • Serum creatinine >2 x ULN. If creatinine 1.5
  • 2.0 x ULN, creatinine clearance will be calculated according to Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula and patients with creatinine clearance <30 mL/min should be excluded.
  • Women who are pregnant or lactating.
  • Documented history of vesicoureteral reflux or an indwelling urinary stent.
  • Participation in any other research protocol involving administration of an investigational agent within 6 weeks prior to study entry.
  • No Institutional Review Board (IRB) approved signed consent form

View trial on ClinicalTrials.gov


{{footer-clinical-trials-navigation}}
{{header-clinical-trials-navigation}}

Electro-Phage and Colorimetric Aptamer Sensors for Clinical Staging and Monitoring of Bladder Cancer


Condition: Urinary Bladder Neoplasms

Study Type: Observational

Clinical Trials Identifier NCT 8-digits: NCT02957370

Sponsor: University of California, Irvine

Phase:

Eligibility:

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

Inclusion Criteria:

  • Patients ≥18 years old
  • Patients with diagnosed bladder cancer, undergoing transurethral resection bladder tumor (TRUBT), or under surveillance (within 2 years) for recurrent bladder cancer
  • Patients with microscopic and macroscopic hematuria
  • Willing and able to consent

Exclusion Criteria:

  • Patients <18 years old
  • Patients who are not able to give consent for study
  • Patients with urinary diversions
  • Patients who have had a recent percutaneous or endoscopic procedures for upper tract diseases such as stones or other conditions
  • Patients who have ureteral stents placed for upper urinary tract obstruction
  • Patients with recent trauma in kidney, bladder or perineal area, which may be the cause of hematuria
  • Minors will be excluded from this study because ureteral stent placement is usually performed in adult patients. Additionally, minors are treated at CHOC Hospital, and not UCIMC.
  • Women who are pregnant are excluded from this study since surgical treatments are not typically performed on pregnant women. Watchful waiting is the preferred approach for pregnant women. Furthermore, this research does not directly benefit the pregnant woman or fetus, and biomedical knowledge can be obtained using subjects who are not pregnant. Therefore, per the federal regulations, pregnant women will be excluded from this study.

View trial on ClinicalTrials.gov


{{footer-clinical-trials-navigation}}
{{header-clinical-trials-navigation}}

A Study of Intravesical Bacillus Calmette-Guerin (BCG) in Combination With ALT-803 (N-803) in Patients With Non-Muscle Invasive Bladder Cancer


Condition: Non-muscle Invasive Bladder Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT02138734

Sponsor: ImmunityBio, Inc.

Phase: Phase 1/Phase 2

Eligibility:

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

Inclusion Criteria:

  • 1. Histologic confirmation of non-muscle invasive bladder cancer of the transitional cell carcinoma high-grade subtype (mixed histology tumors allowed if transitional cell histology is predominant histology). 1. Cohort A: Histologically confirmed CIS (with or without Ta/T1 disease); Cohort B: Histologically confirmed high-grade papillary disease (Ta/T1 only). 2. Patients are eligible if the diagnostic biopsy was done within 3 months of treatment start and a cystoscopy demonstrating no resectable disease was done within 6 calendar weeks (inclusive of 48 days) of treatment start (residual CIS is acceptable; patients with T1 disease must undergo repeat resection if muscularis propria is not present in each biopsy sample). Patients with high-grade Ta and/or T1 disease should have complete resection before study treatment. 3. Upper tract imaging within 6 months prior to study entry must not be suspicious for upper tract malignancy. 2. Currently eligible for intravesical BCG therapy. 3. Age ≥ 18 years. 4. Performance status: ECOG performance status of 0, 1, or 2. 5. Laboratory tests performed within 21 days of treatment start: 1. Absolute neutrophil count (AGC/ANC) ≥ 1,000/µL 2. Platelets ≥ 100,000/µL [Patients may be transfused to meet this requirement] 3. Hemoglobin ≥ 8 g/dL [Patients may be transfused to meet this requirement] 4. Calculated glomerular filtration rate (GFR*) >40 mL/min or Serum creatinine ≤ 1.5 x ULN 5. Total bilirubin ≤ 2.0 X ULN 6. AST, ALT, ALP ≤ 3.0 X ULN 6. Adequate pulmonary function without any clinical sign of severe pulmonary dysfunction. PFT > 50% FEV1 if clinically indicated by the investigator. 7. Negative serum pregnancy test if female and of childbearing potential (non-childbearing is defined as greater than one year postmenopausal or surgically sterilized). 8. Female participants of childbearing potential must adhere to using a medically accepted method of birth control prior to screening and agree to continue its use during the study or be surgically sterilized (e.g., hysterectomy or tubal ligation) and males must agree to use barrier methods of birth control while on study. 9. Provide signed informed consent and HIPPA authorization and agree to comply with all protocol-specified procedures and follow-up evaluations.
  • using the following Cockcroft-Gault equation to calculate the eGFR for this study: eGFR in mL/min = {(140-age in years) x (weight in kg) x F}/(serum creatinine in mg/dL x 72) Where F =1 if male; and 0.85 if female

Exclusion Criteria:

  1. Prior BCG treatment or known hypersensitivity to BCG. Patients who have received more than a single-dose post-operative treatment of mitomycin-C or gemcitabine following the most recent screening TURBT/biopsy are excluded.
  2. Concurrent use of other investigational agents (not including FDA-authorized drugs for the prevention and treatment of COVID-19).
  3. History of or evidence of muscle-invasive, locally advanced, metastatic and/or extravesical bladder cancer or any other cancer within the past 5 years, except: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated stage 1 or 2 cancer from which the patient is currently in complete remission, or stable prostate cancer (under active surveillance or hormone control).
  4. Symptomatic congestive heart failure (CHF), NYHA (New York Heart Association) Class III or IV or other clinical signs of severe cardiac dysfunction.
  5. Severe/unstable angina pectoris, or myocardial infarction within 6 months prior to study entry.
  6. History or evidence of uncontrollable CNS disease.
  7. Known HIV-positive.
  8. Active systemic infection requiring parenteral antibiotic therapy. All prior infections must have resolved following optimal therapy.
  9. Concurrent febrile illness, active urinary tract infection, active tuberculosis, a history of hypotension or anaphylactic reactions.
  10. Ongoing chronic systemic steroid therapy required (>10 mg oral prednisone daily or equivalent).
  11. Women who are pregnant or nursing. Female patients of childbearing potential must have a negative pregnancy test and must adhere to using a medically acceptable method of birth control prior to screening and agree to continue its use during the study and for 30 days after the last dose of study drug, or be surgically sterilized (e.g., hysterectomy or tubal ligation). Women of childbearing potential are defined as any female who has experienced menarche and who is NOT permanently sterile or postmenopausal. Postmenopausal is defined as 12 consecutive months with no menses without an alternative medical cause. Males must agree to use barrier methods of birth control while on study and for 90 days post last dose of study drug.
  12. Psychiatric illness/social situations that would limit compliance with study requirements.
  13. Other illness that in the opinion of the investigator would exclude the patient from participating in this study.

View trial on ClinicalTrials.gov


{{footer-clinical-trials-navigation}}
{{header-clinical-trials-navigation}}

The Role of the Vitamin D Receptor Gene Polymorphisms in Hepatocarcinogenesis in Cirrhotic Patients Infected With Chronic Hepatitis C Virus


Condition: Liver Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT02461979

Sponsor: Sherief Abd-Elsalam

Eligibility:

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

Inclusion Criteria:

  • Hcv cirrhotic patient with and without Hcc

Exclusion Criteria:

  • Malignancy other than HCC
  • Co-infection with Hepatitis B virus (HBV) and Human immunodeficiency virus (HIV)
  • Cirrhosis is due to causes other than chronic hepatitis C

View trial on ClinicalTrials.gov


{{footer-clinical-trials-navigation}}
{{header-clinical-trials-navigation}}

Personalized NK Cell Therapy in Cord Blood Transplantation


Condition: Accelerated Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive, Acute Biphenotypic Leukemia, Acute Lymphoblastic Leukemia, Acute Lymphoblastic Leukemia in Remission, Acute Myeloid Leukemia With Myelodysplasia-Related Changes, Acute Myeloid Leukemia With Variant MLL Translocations, B Acute Lymphoblastic Leukemia With t(9;22)(q34.1;q11.2); BCR-ABL1, Chemotherapy-Related Leukemia, Chronic Myelomonocytic Leukemia, Chronic Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive, High Grade B-Cell Lymphoma With MYC and BCL2 or BCL6 Rearrangements, ISS Stage II Plasma Cell Myeloma, ISS Stage III Plasma Cell Myeloma, Myelodysplastic Syndrome, Myelodysplastic Syndrome With Excess Blasts, Myelodysplastic Syndrome With Gene Mutation, Myelodysplastic/Myeloproliferative Neoplasm, Previously Treated Myelodysplastic Syndrome, Recurrent Acute Myeloid Leukemia, Recurrent Adult Acute Myeloid Leukemia, Recurrent Hodgkin Lymphoma, Recurrent Non-Hodgkin Lymphoma, Refractory Acute Lymphoblastic Leukemia, Refractory Adult Acute Lymphoblastic Leukemia, Secondary Acute Myeloid Leukemia, Therapy-Related Myelodysplastic Syndrome

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT02727803

Sponsor: M.D. Anderson Cancer Center

Phase: Phase 2

Eligibility:

  • Age: minimum 15 Years maximum 80 Years
  • Gender: All

Inclusion Criteria:

  • Patients must have one of the following hematologic malignancies: acute myelogenous leukemia (AML), induction failure, high-risk for relapse first remission (with intermediate-risk or high-risk cytogenetics including complex karyotype, abnormal [abn][3q], -5/5q-, -7/7q-, abn[12p], abn[17p], myeloid/lymphoid or mixed-lineage leukemia [MLL] gene re-arrangement and t [6;9]47, fms related tyrosine kinase 3 [flt3] mutation positive and/or evidence of minimal residual disease by flow cytometry), secondary leukemia from prior chemotherapy and/or arising from myelodysplastic syndromes (MDS), any disease beyond first remission
  • Myelodysplastic syndrome (MDS): Primary or therapy related, including patients that will be considered for transplant; these include any of the following categories: 1) revised International Prognostic Scoring System (IPSS) intermediate and high risk groups, 2) malondialdehyde (MDA) with transfusion dependency, 3) failure to respond or progression of disease on hypomethylating agents, 4) refractory anemia with excess of blasts, 5) transformation to acute leukemia, 6) chronic myelomonocytic leukemia, 7) atypical MDS/myeloproliferative syndromes, 8) complex karyotype, abn(3g), -5/5g-, -7/7g-, abn(12p), abn(17p)
  • Acute lymphoblastic leukemia (ALL): Induction failure, primary refractory to treatment (do not achieve complete remission after first course of therapy) or are beyond first remission including second or greater remission or active disease; patients in first remission are eligible if they are considered high risk, defined as any of the following detected at any time: with translocations 9;22 or 4;11, hypodiploidy, complex karyotype, secondary leukemia developing after cytotoxic drug exposure, and/or evidence of minimal residual disease or acute biphenotypic leukemia, or double hit non-Hodgkin's lymphoma
  • Non-Hodgkin's lymphoma (NHL) in second or third complete remission, or relapse (including relapse post autologous hematopoietic stem cell transplant); relapsed double hit lymphomas; patients with options for treatment that are known to be curative are not eligible
  • Small lymphocytic lymphoma (SLL), or chronic lymphocytic leukemia (CLL) with progressive disease following a minimum of two lines of standard therapy
  • Chronic myeloid leukemia (CML) second chronic phase or accelerated phase
  • Hodgkin's disease (HD): Induction failures, after first complete remission, or relapse (including relapse post autologous hematopoietic stem cell transplant), or those with active disease
  • Multiple myeloma: stage II or III, symptomatic, secretory multiple myeloma requiring treatment
  • A person (such as a haploidentical family member) or unit of cord blood must be identified as a source of back-up cells source in case of engraftment failure
  • Patient age criteria: age >= 15 and =< 45 years (myeloablative regimen 1; age >= 15 and =< 80 years (nonmyeloablative regimen 2) at the discretion of the investigator(s); age >= 15 and =< 80 years old that in the opinion of the investigator(s) would preclude myeloablative therapy may receive reduced intensity regimen 3
  • Performance score of at least 60% by Karnofsky
  • Left ventricular ejection fraction of at least 40% (myeloablative regimen 1, reduced intensity regimen 3)
  • Left ventricular ejection fraction of at least 30% (nonmyeloablative regimen 2)
  • Pulmonary function test (PFT) demonstrating an adjusted diffusion capacity of least 50% predicted value for hemoglobin concentration (myeloablative regimen 1, reduced intensity regimen 3)
  • Serum creatinine within normal range, or if serum creatinine outside normal range, then renal function (measured or estimated creatinine clearance or glomerular filtration rate [GFR]) > 40mL/min/1.73 m^2
  • Serum glutamate pyruvate transaminase (SGPT)/bilirubin < to 2.0 x normal (myeloablative regimen 1), reduced intensity regimen 3; SGPT/bilirubin < to 4.0 x normal (nonmyeloablative regimen 2)
  • Negative beta human chorionic gonadotropin (HCG) test in a woman with child bearing potential defined as not post-menopausal for 12 months
  • Patients with options for treatment that are known to be curative are not eligible
  • Patients enrolled in this study may be enrolled on other supportive care investigational new drug (IND) studies at the discretion of the principal investigator (PI)

Exclusion Criteria:

  • Human immunodeficiency virus (HIV) positive; HIV results will be determined by nucleic acid testing
  • Uncontrolled serious medical condition such as persistent septicemia despite adequate antibiotic therapy, decompensated congestive heart failure despite cardiac medications or pulmonary insufficiency requiring intubation (excluding primary disease for which cord blood [CB] transplantation is proposed), or psychiatric condition that would limit informed consent
  • Active central nervous system (CNS) disease in patient with history of CNS malignancy
  • Availability of appropriate, willing, human leukocyte antigen (HLA)-matched related stem cell donor

View trial on ClinicalTrials.gov


{{footer-clinical-trials-navigation}}
{{header-clinical-trials-navigation}}

Phase I Study of Hypofractionated Radiotherapy and Anti-PD1 Antibody (Pembrolizumab) in the Treatment of Advanced Bladder Cancer


Condition: Invasive Bladder Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT02560636

Sponsor: Royal Marsden NHS Foundation Trust

Phase: Phase 1

Eligibility:

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

Inclusion Criteria:

  1. Histologically confirmed invasive bladder.carcinoma (T2-4,N0-3,M0-1).
  2. Be willing and able to provide written informed consent for the trial.
  3. Be ≥ 18 years of age on day of signing informed consent.
  4. Have measurable disease based on RECIST 1.
  5. , or, in group A, disease assessable by cystoscopic assessment.
  6. Have consented to analysis of tissue from an archival tissue sample
  7. Have a performance status of 0-1 on the ECOG Performance Scale.
  8. Planned for hypofractionated radiotherapy
  9. Demonstrate adequate organ function as defined in table 2 (please see protocol) all screening blood tests should be performed within 10 days of confirmation of eligibility.
  10. Female subject of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to confirmation of study eligibility. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
  11. Female subjects of childbearing potential should 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 120 days 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 > 1 year.
  12. Male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy if their partner has childbearing potential (as defined by not being surgically sterilized or have not been free from menses for > 1 year).

Exclusion Criteria:

  • The subject must be excluded from participating in the trial if the subject: 1. Is currently participating in or has participated in a study of an investigational agent or using an investigational device within 4 weeks of the first dose of treatment. 2. Previous pelvic radiotherapy, history of inflammatory bowel disease or other conditions that would in the opinion of the investigator would preclude the safe administration of pelvic radiotherapy. 3. Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy (>dose equivalent to 10mg of Prednisolone/day) or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment. 4. Has had a prior monoclonal antibody within 4 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier. 5. Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 4 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent or therapy.
  • Note: Subjects with ≤ Grade 2 neuropathy or chemotherapy induced alopecia/nail changes are an exception to this criterion and may qualify for the study.
  • Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy. 6. Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, localized prostate cancer (≤T2 ≤ Gl3+4) or in situ cervical cancer that has undergone potentially curative therapy. Patients may have received treatment for previous urothelial malignancy. 7. 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 four 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. 8. Has an active autoimmune disease requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents. Subjects with vitiligo or resolved childhood asthma/atopy would be an exception to this rule. Subjects that require intermittent use of bronchodilators or local steroid injections would not be excluded from the study. Subjects with hypothyroidism stable on hormone replacement or Sjorgen's syndrome will not be excluded from the study. 9. Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis. 10. Has an active infection requiring systemic therapy. 11. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator. 12. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial. 13. 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. 14. Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways). 15. Has a known history of Human Immunodeficiency Virus (HIV). 16. Has known clinical history of Hepatitis B or Hepatitis C . 17. Has received a live vaccine within 30 days prior to the first dose of trial treatment.

View trial on ClinicalTrials.gov


{{footer-clinical-trials-navigation}}
{{header-clinical-trials-navigation}}

MDSC Clinical Assay for Cancer Detection and Monitoring in Bladder Carcinoma


Condition: No Evidence of Disease, Stage II Bladder Cancer, Stage III Bladder Cancer, Stage IVA Bladder Cancer, Stage IVB Bladder Cancer

Study Type: Observational

Clinical Trials Identifier NCT 8-digits: NCT02735512

Sponsor: University of Southern California

Phase:

Eligibility:

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

Inclusion Criteria:

  • Subjects must meet the criteria for one of the three following groups:
  • Normal patients- aged 40 years and older with no evidence of hematuria or cancer
  • Patients with localized bladder cancer diagnosed by cystoscopy and pathology: T2N0M0 or T3N0M0 who have not received neoadjuvant chemotherapy
  • Patients with metastatic bladder cancer: newly diagnosed with no previous treatment for metastatic disease
  • Ability to understand and the willingness to sign a written informed consent

Exclusion Criteria:

  • For normal subject arm: evidence of cancer or hematuria
  • For localized bladder cancer: evidence of metastatic disease, second cancer, prior chemotherapy or radiotherapy within 4 weeks prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
  • For metastatic bladder cancer: prior therapy for metastatic disease
  • Uncontrolled intercurrent illness including, but not limited to previous or current history of second malignancy unrelated to bladder cancer; autoimmune disease or immune deficiency, chronic treatment with immunomodulatory therapies (e.g. glucocorticoids); significant trauma, surgery, or infection in the past two weeks or psychiatric illness/social situations that would limit compliance with study requirements

View trial on ClinicalTrials.gov


{{footer-clinical-trials-navigation}}
{{header-clinical-trials-navigation}}

Adjuvant Chemotherapy With Gemcitabine and Cisplatin Compared to Standard of Care After Curative Intent Resection of Cholangiocarcinoma and Muscle Invasive Gall Bladder Carcinoma (ACTICCA-1 Trial)


Condition: Cholangiocarcinoma, Gall Bladder Carcinoma

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT02170090

Sponsor: Universitätsklinikum Hamburg-Eppendorf

Phase: Phase 3

Eligibility:

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

Criteria: All enrolled patients will postoperatively be assessed for eligibility for the treatment phase. Additionally patients not previously enrolled into the trial for whatever reason (e.g. incidental finding during surgery) will be evaluated for eligibility. - Histologically confirmed adenocarcinoma of biliary tract (intrahepatic, hilar or extrahepatic cholangiocarcinoma or muscle invasive gallbladder carcinoma) after radical surgical therapy with macroscopically complete resection (mixed tumor entities (HCC/CCA) are excluded) - Macroscopically complete resection (R0/1) within 6 (-16) weeks before scheduled start of chemotherapy - ECOG 0-1 - Age ≥18 years - Adequate hematologic function - Adequate liver function - Adequate renal function - No active uncontrolled infection, except chronic viral hepatitis under antiviral therapy - No concurrent treatment with other experimental drugs or other anti-cancer therapy, treatment in a clinical trial within 30 days prior to randomization - Negative serum pregnancy test within 7 days of starting study treatment in pre-menopausal women and women <1 year after the onset of menopause (Note: a negative test has to be reconfirmed by a urine test, should the 7-day window be exceeded) Criteria for initial study enrolment - Written informed consent - No prior chemotherapy for cholangiocarcinoma - No previous malignancy within 3 years or concomitant malignancy, except: non-melanomatous skin cancer or adequately treated in situ cervical cancer - No severe or uncontrolled cardiovascular disease (congestive heart failure NYHA III or IV, unstable angina pectoris, history of myocardial infarction in the last 3 months, significant arrhythmia) - Absence of psychiatric disorder precluding understanding of information of trial related topics and giving informed consent - No serious underlying medical conditions (judged by the investigator), that could impair the ability of the patient to participate in the trial - Fertile women (< 1 year after last menstruation) and procreative men willing and able to use effective means of contraception (oral contraceptives, intrauterine contraceptive device, barrier method of contraception in conjunction with spermicidal jelly or surgically sterile) - No pregnancy or lactation

View trial on ClinicalTrials.gov


{{footer-clinical-trials-navigation}}
{{header-clinical-trials-navigation}}

Prospective Randomized Trial of Adjuvant Radiotherapy Following Surgery and Chemotherapy in Muscle Invasive Transitional Cell Carcinoma of Urinary Bladder


Condition: Bladder Cancer, Urothelial Carcinoma Bladder

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT02951325

Sponsor: Tata Memorial Centre

Eligibility:

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

Inclusion Criteria:

  • All patients should have undergone radical cystoprostatectomy for bladder cancer Patients with any of the below high risk features on histolopathology
  • Lymph Node positive with or without perinodal extension (PNE)
  • Cut-margin positive,
  • pT3 and pT4 disease,
  • Number of nodes dissected at surgery < 10 All patients irrespective of the final pathology if they have received neo-adjuvant chemotherapy prior to surgery for any of the following T3 T4 stage N1-3 stage No evidence of distant metastasis including para-aortic nodal metastasis KPS ≥ 70 Signed study specific consent form Adequate hepatic, renal and hematologic parameters

Exclusion Criteria:

  • Contraindication to pelvic radiotherapy like inflammatory bowel disease
  • Uncontrolled diabetes or hypertension
  • Uncontrolled cardiac or respiratory co morbidity
  • Prior history of therapeutic irradiation to pelvis
  • Patient unwilling and unreliable for follow up and QoL

View trial on ClinicalTrials.gov


{{footer-clinical-trials-navigation}}
{{header-clinical-trials-navigation}}

Lymphadenectomy in Urothelial Carcinoma in the Renal Pelvis and Ureter


Condition: Ureteral Neoplasms

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT02607709

Sponsor: Zealand University Hospital

Eligibility:

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

Inclusion Criteria:

  1. Age above 18 years
  2. Locally advanced high grade urothelial carcinoma in the renal pelvis or upper 2/3 of the ureter (Clinical stage > T1)
  3. Patient with ECOG performance score of 2 and less.
  4. Able to give informed consent

Exclusion Criteria:

  1. Clinical suspicion of non-muscle invasive UUTUC
  2. Metastatic urothelial carcinoma for the renal pelvis or upper 2/3 of the ureter
  3. Inability to understand written consent forms or give consent

View trial on ClinicalTrials.gov


{{footer-clinical-trials-navigation}}
email news signup