Adjuvant Sacituzumab Govitecan and Nivolumab in Muscle-Invasive Urothelial Carcinoma at High-Risk Recurrence
- Conditions
- Interventions
- Registration Number
- NCT06682728
- Lead Sponsor
- University of California, Irvine
- Brief Summary
This is a phase 2 study, single-arm study of adjuvant combination therapy with Sacituzumab Govitecan and Nivolumab in patients with muscle-invasive urothelial carcinoma of the bladder, ureter, or upper tract, who are high risk for cancer recurrence post curative-intent surgery based on surgical pathology.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 23
- Age ≥ 18 years at the time of study consent.
- ECOG Performance Status of 0, 1 or 2 (see Appendix A).
- Histologically confirmed muscle-invasive UC originating in the bladder, ureter, or renal pelvis. Variant histology, except small cell carcinoma, is allowed.
- Underwent curative-intent surgery, including radical cystectomy or nephroureterectomy.
within 180 days prior to study treatment initiation.
- Radiographic disease-free status as determined by imaging within 28 days of C1 D1 of study treatment.
- Prior platinum-based neoadjuvant chemotherapy (NAC) is allowed. If chemotherapy-naive, patient must be Cisplatin-ineligible (based on Galsky et al 2011 [10]) or refuse platinum adjuvant chemotherapy.
- Prior treatment with neoadjuvant investigational agents is allowed (except PD-1/PD-L1 inhibitors) or Sacituzumab Govitecan. No washout from neoadjuvant therapy is required.
- If NAC was given, patient must be considered at high risk for cancer recurrence due to having pathologic T2, T3, T4, or N+ disease on the radical cystectomy or nephroureterectomy surgical specimen.
- If no NAC was given, patient must be considered at high risk for cancer recurrence due to having pathologic T3, T4, or N+ disease on the radical cystectomy or nephroureterectomy surgical specimen.
- Adequate organ and marrow function as defined below:
- ANC ≥ 1000/mcL
- Platelets ≥ 100,000/mcL
- Total bilirubin ≤ 1.5 × institutional ULN (or ≤ 3.0 × ULN for subjects with Gilbert's disease)
- AST/ALT ≤ 3 × institutional ULN
- Alkaline phosphatase ≤ 3 × institutional ULN
- Serum albumin ≥ 2.8 g/dL
- Creatinine Creatinine clearance of ≥30 mL/min (calculated with Cockroft- Gault formula)
- Hemoglobin ≥ 9.0 g/dL
- aPTT ≤ 1.3 × institutional ULN
- Sexually active fertile subjects and their partners must agree to use medically accepted methods of contraception.
- Female subjects of childbearing potential must not be pregnant following signing the study consent form.
- Recovery to ≤ Grade 1 of CTCAE version 5 toxicities related to any prior treatment for UC, unless AE(s) is clinically non-significant and/or stable on supportive therapy as per discretion of the Investigator.
- Ability to understand and the willingness to sign a written informed consent.
- Underwent a partial cystectomy or partial nephrectomy.
- History of adjuvant platinum-based chemotherapy or any other type of adjuvant therapy following surgical removal of UC.
- History of treatment with PD-1/PD-L1 inhibitors or Sacituzumab Govitecan prior to study treatment initiation.
- History of previous radiation therapy for treatment of UC.
- Radiographic evidence of metastasis.
- Receipt of or planning to receive any other concurrent investigational agents.
- History of active, known, or suspected autoimmune disease.
- Conditions requiring treatment with either systemic high-dose corticosteroids or other immunosuppressive medications within 14 days of study treatment initiation.
- History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan.
- Major surgery within 28 days or minor surgery within 14 days before the first dose of study treatment.
- Active malignancy within 3 years of study entry, except treated localized non- melanoma skin cancer, Gleason 6 prostate cancer on active surveillance, or curatively treated in situ cancer of the breast or cervix.
- Patients who do not have adequate organ and marrow function.
- Uncontrolled intercurrent illness.
- Received a live vaccine within 30 days prior to the first dose of study treatment.
- Known or suspected severe hypersensitivity (Grade ≥ 3) to Nivolumab, Sacituzumab Govitecan, Irinotecan, and/or any of their components.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Sacituzumab Govitecan PLUS Nivolumab Sacituzumab Govitecan (SG) Patients eligible for this study treatment will receive combination therapy with Sacituzumab Govitecan with Nivolumab for 4 cycles, followed by single-agent Nivolumab for an additional 11 cycles. Sacituzumab Govitecan PLUS Nivolumab Nivolumab Patients eligible for this study treatment will receive combination therapy with Sacituzumab Govitecan with Nivolumab for 4 cycles, followed by single-agent Nivolumab for an additional 11 cycles.
- Primary Outcome Measures
Name Time Method Primary Objective 6 months after last patient enrollment To determine investigator-assessed disease-free survival (DFS) at 6 months.
- Secondary Outcome Measures
Name Time Method Secondary (1) Time from Cycle1 Day 1 of study treatment to first occurrence of a disease free survival event, up to 5 years. To determine investigator-assessed DFS (i.e. time from Cycle 1 Day 1 (C1D1) of study treatment to first occurrence of a DFS event), defined as any of the following:
1. Local (pelvic) recurrence of UC (including regional lymph nodes)
2. Urinary tract recurrence of UC (including all pathological stages and grades)
3. Distant metastasis of UC
...Secondary (2) Time from Cycle 1 Day 1 of study treatment to diagnosis of distant metastases or death from any cause, up to 5 years. To determine investigator-assessed distant metastasis-free survival (MFS) (i.e. time from Cycle 1 Day 1 of study treatment to diagnosis of distant metastases or death from any cause).
Secondary (3) Time from C1D1 of study treatment to death of any cause, up to 5 years. To determine overall survival (OS) (i.e. time from Cycle 1 Day 1 of study treatment to death of any cause).
Secondary (4) Up to 5 years To determine incidence of Grade 3 or higher AEs.
Secondary (5) Conversion from positive ctDNA to negative at any point from baseline assessment, up to 5 years. To determine rate of ctDNA clearance in ctDNA positive patients (i.e. conversion from positive ctDNA to negative at any point from baseline assessment).
Secondary (6) Up to 5 years To perform exploratory biomarker analysis.
Trial Locations
- Locations (1)
Chao Family Comprehensive Cancer Center, University of California, Irvine
🇺🇸Orange, California, United States