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Back|NCT03547973Recruiting
Official Title

A Phase II Open-Label Study of Sacituzumab Govitecan in Unresectable Locally Advanced/Metastatic Urothelial Cancer

Phase
Phase 2
Sponsor
Gilead Sciences
Enrollment
827
Timeline
Aug 2018 → Jun 2030
About This Study

The objective of this study is to evaluate the efficacy and safety of sacituzumab govitecan-hziy monotherapy and with novel combinations in participants with metastatic urothelial cancer (mUC).

Eligibility Criteria

Inclusion Criteria

  • 1Female or male individuals, ≥ 18 years of age (19 Years old for South Korea).
  • 2Eastern Cooperative Oncology Group (ECOG) Performance status score of 0 or 1.
  • 3Adequate renal and hepatic function.
  • 4Adequate hematologic parameters without transfusional support.
  • 5Individuals must have a 3-month life expectancy.
  • 6Cohort 1: Have had progression or recurrence of urothelial cancer following receipt of platinum-containing regimen (cisplatin or carboplatin):
  • 7Received a first-line platinum-containing regimen in the metastatic setting or for inoperable locally advanced disease;
  • 8Or received neo/adjuvant platinum-containing therapy for localized muscle-invasive urothelial cancer, with recurrence/progression ≤12 months following completion of therapy.
  • 9Cohort 1: In addition to above criterion, have had progression or recurrence of urothelial cancer following receipt of an Anti-programmed Cell Death Protein 1 (anti-PD-1)/ Anti-programmed Death Ligand 1 (PD-L1) therapy.
  • 10Cohort 2: Were ineligible for platinum-based therapy for first line metastatic disease and have had progression or recurrence of urothelial cancer after a first-line therapy for metastatic disease with anti-PD-1/PD-L1 therapy. Individual may not have received any platinum for treatment of recurrent, metastatic or advanced disease.
  • 11Cohort 3: Progression or recurrence of UC following a platinum containing regimen in the metastatic setting, or progression or recurrence of UC within 12 months of completion of platinum-based therapy as neoadjuvant or adjuvant therapy.
  • 12Cohort 4: Individual has not received any platinum-based chemotherapy in the metastatic or unresectable locally advanced setting. Creatinine clearance of at least 50 mL/min calculated by Cockcroft-Gault formula or another validated tool. For individuals receiving cisplatin at 70 mg/m\^2 on Day 1 of every 21-day cycle, a creatinine clearance of least 60 mL/min calculated by Cockcroft -Gault formula or another validated tool is required. Individuals with creatinine clearance between 50 to 59 mL/min are to receive a split dose of cisplatin (35 mg/m\^2 Day 1 and Day 8 of every 21-day cycle).
  • 13Cohorts 4, 5, 6: Archival tumor tissue comprising muscle-invasive or metastatic urothelial carcinoma, or a biopsy of metastatic urothelial carcinoma.
  • 14Cohort 5: Individuals received at least 4 cycles and no more than 6 cycles of GEM + cisplatin. No other chemotherapy regimens are allowed in this cohort, with the exception of prior adjuvant or neoadjuvant systemic therapy with curative intent after \> 12 months from completion of therapy.
  • 15No evidence of progressive disease following completion of first-line chemotherapy (ie, CR, PR, or SD per RECIST v1.1 guidelines as per investigator).
  • 16Treatment-free interval of 4 to 10 weeks since the last dose of chemotherapy.
  • 17Cohort 6: Cis-ineligible and no prior therapy for metastatic disease or for unresectable locally advanced disease. Checkpoint inhibitor therapy naïve or \>12 months from completion of adjuvant therapy are permitted.
  • 18Cohorts 4 and 6: Have measurable disease by CT or MRI as per RECIST 1.1 criteria. Tumor lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
  • 19Cohorts 1, 2, 3 and 5: Creatinine clearance ≥ 30 mL/min as calculated by the Cockcroft-Gault formula unless otherwise specified
  • 20No prior systemic therapy for locally advanced or metastatic UC. Therapy in the curative setting is allowed provided recurrence is \> 12 months since the last dose of systemic therapy.
  • 21Archival tumor tissue comprising muscle-invasive or metastatic urothelial carcinoma, or a biopsy of metastatic urothelial carcinoma.
  • 22Have measurable disease by CT or MRI as per RECIST 1.1 criteria. Tumor lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.

Exclusion Criteria

  • 1Females who are pregnant or lactating.
  • 2Has had a prior anti-cancer monoclonal antibody (mAb) 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.
  • 3Has an active second malignancy.
  • 4Has known active Hepatitis B or Hepatitis C.
  • 5Has other concurrent medical or psychiatric conditions.
  • 6Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
  • 7Has an active second malignancy.
  • 8For Cohort 5: Alopecia, sensory neuropathy Grade ≤2 is acceptable, or other Grade \<\< 2 adverse events not constituting a safety risk based on the investigator's judgment are acceptable.
  • 9Cohort 3: Has received anti-PD-1/PD-L1 therapy previously.
  • 10Cohorts 3 to 6: Has an active autoimmune disease that required systemic treatment in past 2 years (ie, with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment.
  • 11Cohorts 3 to 6: Has received a live vaccine within 30 days prior to the first dose of study drug(s), has history or evidence of interstitial lung disease (ILD) or non-infectious pneumonitis.
  • 12Cohort 4: Refractory to platinum (i.e., relapsed ≤ 12 months after completion of chemotherapy) in the neoadjuvant/adjuvant setting.
  • 13Cohorts 4, 5, and 6: For individuals who received prior CPI, a treatment-free interval \>12 months between the last treatment administration and the date of recurrence is required.
  • 14Have had a prior anticancer therapy within 12 months prior to C1D1 or prior radiation therapy within 2 weeks prior to C1D1. Individuals participating in observational studies are eligible. Use of other investigational drugs (drugs not marketed for any indication) within 28 days or 5 half-lives (whichever is longer) of first dose of investigational product.
  • 15Have a history of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan.
  • 16Have a Child-Pugh score of B or C.
  • 17Individuals with uncontrolled diabetes.
  • 18Have active keratitis or corneal ulcerations.
  • 19Participants with ongoing sensory or motor neuropathy Grade ≥ 2.

Locations

135 sites participating in this study

Winship Cancer Institute, Emory University

Atlanta, Georgia 30322

Completed

The University of Arizona Cancer Center-North Campus

Tucson, Arizona 85719

Recruiting

USC/Norris Comprehensive Cancer Center

Los Angeles, California 90033

Withdrawn
Data sourced from ClinicalTrials.govView on ClinicalTrials.gov →