Study of Sacituzumab Govitecan in Subjects with Urothelial Cancer That Cannot Be Removed or Has Spread
- Conditions
- Histologically documented locally advanced (tumor [T] 4b, any node [N]or any T, N 2-3) or metastatic (M1, Stage IV) urothelial carcinoma of the urinary tract predominantMedDRA version: 21.1Level: LLTClassification code 10077840Term: Urothelial cancer of renal pelvisSystem Organ Class: 100000004864MedDRA version: 20.0Level: LLTClassification code 10046714Term: Urothelial carcinoma bladderSystem Organ Class: 100000004864MedDRA version: 20.0Level: LLTClassification code 10046723Term: Urothelial carcinoma ureterSystem Organ Class: 100000004864MedDRA version: 20.0Level: LLTClassification code 10046728Term: Urothelial carcinoma urethraSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2018-001167-23-IT
- Lead Sponsor
- GILEAD SCIENCES INCORPORATED
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 421
1. Female or male subjects, >=18 years of age, able to understand and give written informed consent.
2. Subjects with histologically documented locally advanced (tumor [T] 4b, any node [N]; or any T, N 2-3) or metastatic (M1, Stage IV) UC. Upper and lower tract tumors are permitted and mixed histologies are permitted if UC is the predominant histology.
3. Cohorts 4, 5 and 6: Archival tumor tissue comprising muscle-invasive or metastatic urothelial carcinoma, or a biopsy of metastatic urothelial carcinoma must be provided for biomarker testing including PD-L1 and Trop-2.
4. ECOG Performance status score of 0 or 1.
5. Cohort 1: Have had progression or recurrence of UC following receipt of platinum-containing regimen (cisplatin or carboplatin):
a) Received a first-line platinum-containing regimen in the metastatic setting or for inoperable locally advanced disease;
b) Or received neo/adjuvant platinum-containing therapy for localized muscle-invasive urothelial cancer, with recurrence/progression =12 months following completion of therapy.
6. Cohort 1: In addition to criterion #5, have had progression or recurrence of UC following receipt of an anti-PD-1 /PD-L1 therapy and have a creatinine clearance = 60 ml/min.
7. Cohort 2: Were ineligible for platinum-based therapy* and have had progression or recurrence of UC therapy for metastatic disease with anti-PD-
1/PD-L1 therapy. Subject may not have received any platinum for treatment of recurrent, metastatic or advanced disease.
8. * Cisplatin-ineligible
9. Cohort 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
10. Cohort 4: Cisplatin-eligible subject who has not received any therapy, specifically platinum-based chemotherapy in the metastatic or unresectable locally advanced setting.
11. Cohort 1, 2, 3: Adequate hematology without transfusion support or growth factor support within 2 weeks of study drug initiation (hemoglobin > 9 g/dL, absolute neutrophil count (ANC) > 1,500 per mm3, and Platelets > 100,000 per mcL).
12. Cohort 6: Subject with no prior therapy for metastatic disease or for unresectable locally advanced disease with the following exceptions:
a) Subjects who received neoadjuvant chemotherapy with curative intent with recurrence >12 months from completion of therapy are permitted.
b) Subjects who received adjuvant chemotherapy following cystectomy with curative intent with recurrence > 12 months from completion of therapy are permitted.
13. Cohort 6: Cisplatin-ineligible:
14. Cohort 6: Checkpoint inhibitor therapy naïve or >12 months from completion of for adjuvant therapy are permitted.
15. Cohorts 4, 5 and 6: Adequate hematology without transfusion support or growth factor support within 2 weeks of study drug initiation (Total WBC count must be =4000 per mm3, ANC =1500 per mm3, platelets =100,000 per mcL, and hemoglobin =9 g/dL).
16. Adequate hepatic function (Bilirubin = 1.5 ULN, AST and ALT = 2.5 x ULN or = 5 x ULN if known liver metastases and serum albumin >/=3 g/dl)).
17. Cohorts 1-3 and 5-6: Creatinine clearance >/= 30mL/min as calculated by the Cockroft-Gault formula unless otherwise specified.
18. Cohort 4: Creatinine clearance of at least 50 mL/min calculated by Cockcroft–Gault formula or another validated tool. For subjects receiving cisplatin at 70 mg/m2 on Day 1 of every 21-day cycle, a
1. Women who are pregnant or lactating.
2. Is currently participating in or has participated in a study of an investigational agent or using an investigational device within 4 weeks prior to the first dose of trial treatment.
3. Has a diagnosis of immunodeficiency.
4. Has had a prior anti-cancer mAb within 4 weeks prior to study Day 1 or who has not recovered (i.e., = Grade 1) 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 2 weeks prior to study Day 1 or who has not recovered (i.e., = Grade 1 from adverse events due to a previously administered agent.
Note: Subjects with = Grade 2 neuropathy or = Grade 2 alopecia 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. Cohorts 4 and 5: Refractory to platinum ( in the neoadjuvant/adjuvant setting.
7. Requires concomitant medications that significantly interfere with ABCA1 transporter or UGT1A1 with no alternate option available.
8. Subjects with Gilbert’s disease.
9. Subjects who previously received irinotecan.
10. Has an active second malignancy.
11. Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they have stable CNS disease for at least 4 weeks prior to the first dose of study drug and all neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids greater than 20 mg of prednisone daily for brain metastases for at least 7 days prior to trial treatment. All subjects with carcinomatous meningitis are excluded regardless of clinical stability.
12. Has active cardiac disease, defined as:
a. Myocardial infarction or unstable angina pectoris within 6 months of the first date of study therapy.
b. History of serious ventricular arrhythmia , high-grade atrioventricular block, or other cardiac arrhythmias requiring antiarrhythmic medications (except for atrial fibrillation that is well controlled with antiarrhythmic medication); history of QT interval prolongation.
c. New York Heart Association Class III or greater congestive heart failure or left ventricular ejection fraction of < 40%.
13. Has active chronic inflammatory bowel disease and subjects with a history of bowel obstruction.
14. Has prior history of clinically significant bleeding, intestinal obstruction, or GI perforation within 6 months of enrollment.
15. Must be at least 2 weeks beyond high dose systemic corticosteroids (however, low dose corticosteroids = 20 mg prednisone or equivalent daily are permitted for reasons outside of CNS disease provided the dose is stable for 4 weeks).
16. Has an active infection requiring systemic therapy.
17. Have known history of HIV-1 or 2 with uncontrolled viral load (ie, = 200 copies/mL or CD4+ T-cell count < 350 cells/µL) or taking medications that may interfere with metabolism of study drugs. No HIV testing is required unless mandated by local health authority.
For other exclusion criteria please refer to the protocol.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method