Sacituzumab Govitecan With or Without Atezolizumab Immunotherapy in Rare Genitourinary Tumors (SMART) Such as High Grade Neuroendocrine Carcinomas, Adenocarcinoma, and Squamous Cell Bladder/Urinary Tract Cancer, Renal Medullary Carcinoma and Penile C...
- Conditions
- Small Cell Carcinoma of the BladderSquamous Cell Carcinoma of the Urinary TractSmall Cell Carcinoma of the Urinary TractRenal Medullary CarcinomaPrimary Adenocarcinoma of the BladderPrimary Adenocarcinoma of the Urinary TractSquamous Cell Carcinoma of the BladderSquamous Cell Carcinoma of the Penis
- Interventions
- Registration Number
- NCT06161532
- Lead Sponsor
- National Cancer Institute (NCI)
- Brief Summary
Background:
Rare tumors of the genitourinary (GU) tract can appear in the kidney, bladder, ureters, and penis. Rare tumors are difficult to study because there are not enough people to conduct large trials for new treatments. Two drugs-sacituzumab govitecan (SG) and atezolizumab-are each approved to treat other cancers. Researchers want to find out if the two drugs used together can help people with GU.
Objective:
To test SG, either alone or combined with atezolizumab, in people with rare GU tumors.
Eligibility:
Adults aged 18 years and older with rare GU tumors. These may include high grade neuroendocrine carcinomas; squamous cell carcinoma of the bladder; primary adenocarcinoma of the bladder; renal medullary carcinoma; or squamous cell carcinoma of the penis.
Design:
Participants will be screened. They will have a physical exam with blood and urine tests. They will have tests of heart function. They will have imaging scans. They may need a biopsy: A small needle will be used to remove a sample of tissue from the tumor.
Both SG and atezolizumab are given through a tube attached to a needle inserted into a vein in the arm.
All participants will receive SG on days 1 and 8 of each 21-day treatment cycle. Some participants will also receive atezolizumab on day 1 of each cycle.
Blood and urine tests, imaging scans, and other exams will be repeated during study visits.
Treatment may continue for up to 5 years.
Follow-up visits will continue for 5 more years.
...
- Detailed Description
Background:
* Urothelial carcinoma (UC) represents the most common histology for tumors of the bladder and urinary tract.
* A minority of patients have primary tumors of the bladder/urinary tract consisting of rare histological variants, including high grade neuroendocrine carcinomas (HGNEC), primary adenocarcinoma of the bladder (urachal or non-urachal), or squamous cell carcinoma. Some tumors may contain elements of UC mixed with these variants or may be entirely composed of such variants.
* Clear cell renal cell carcinoma (ccRCC) is the most common histology for cancers of the renal parenchyma. Renal medullary carcinoma is a rare histology of kidney cancer, which is associated with sickle cell trait and other hemoglobinopathies.
* Rare tumors of the genitourinary (GU) tract often have more aggressive clinical course, but lack standard of care treatment regimens, since these patient populations are poorly represented or excluded from most clinical trials.
* Sacituzumab govitecan (SG) is an antibody-drug conjugate of an IgG 1 monoclonal antibody targeting trophoblastic cell surface antigen 2 (Trop2) with a chemotherapeutic payload of SN-38. SN-38 is an active metabolite of irinotecan and acts as a topoisomerase I inhibitor.
* SG has demonstrated clinical activity in solid tumors. In phase II clinical trials, SG has demonstrated efficacy in metastatic UC after progression on platinum-based chemotherapy and immune checkpoint inhibitor (ICI) therapy.
* Atezolizumab is an anti- programmed death-ligand 1 (PD-L1) ICI that is approved for advanced/metastatic UC in patients ineligible to receive platinum therapy.
* There are currently no clinical trials for SG monotherapy or SG/atezolizumab combination in rare GU tumors.
Objective:
-To determine clinical efficacy of sacituzumab govitecan (SG), either alone or in combination with atezolizumab, as defined by objective response rate (ORR), in participants with rare metastatic non-prostate genitourinary tumors
Eligibility:
* Age \>= 18 years
* ECOG performance status \<= 1
* Histologically confirmed diagnosis of locally advanced (unresectable) or metastatic GU tumors of the following histologies: high grade neuroendocrine carcinomas (HGNEC), squamous cell carcinoma, or primary adenocarcinoma of the bladder or urinary tract; or renal medullary carcinoma or squamous cell carcinoma of the penis.
* Participants must have locally advanced unresectable or metastatic disease on cross-sectional imaging.
* Participants may have received any prior programmed cell death protein 1 (PD-1)/PD-L1 axis ICI treatment.
Design:
* This is an open label, non-randomized phase II trial with two arms.
* All participants will receive SG.
* Participants without prior treatment with any PD-1/PD-L1 axis ICI (checkpoint inhibitor na(SqrRoot) ve) will be eligible to receive concurrent atezolizumab.
* SG will be administered intravenously (IV) at 10 mg/kg on D1 and D8 of 21-day cycles.
* Atezolizumab will be administered IV at 1200mg on D1 of 21-day cycles.
* Treatment will be given in 21-day cycles continuously for a maximum of 5 years, or until signs of progression or intolerable side effects.
* The accrual ceiling will be set at 60 to allow for inevaluable participants and screen failure.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 60
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm 2 Sacituzumab govitecan Treatment with sacituzumab govitecan and atezolizumab Arm 1 Sacituzumab govitecan Treatment with sacituzumab govitecan Arm 2 Atezolizumab Treatment with sacituzumab govitecan and atezolizumab
- Primary Outcome Measures
Name Time Method Objective response rate (ORR) On days 1 and 8 of each cycle and at every restaging (every 9 weeks) until the end of the study therapy and every 9 weeks during follow-up until PD. Percentage of participants by best overall response (e.g., CR, PR, SD, PD) to therapy
- Secondary Outcome Measures
Name Time Method Progression-free survival (PFS) At every restaging (every 9 weeks) until the end of the study therapy and every 9 weeks during follow-up until PD Duration of time from start of treatment to time of progression or death, whichever occurs first
Duration of response (DoR) On days 1 and 8 of each cycle and at every restaging (every 9 weeks) until the end of the study therapy and every 9 weeks during follow-up until PD. Time from start of treatment to disease progression or death in participants who achieve CR or PR
Overall survival (OS) Days 1 and 8 of each cycle, at EoT, at the Safety visit, at follow-up, and every 90 days for up to a total of 5 years after the end of therapy Time from the start of treatment that participants are still alive.
Clinical benefit rate (CBR) At every restaging (every 9 weeks) until the end of the study therapy and every 9 weeks during follow-up until PD Percentage of participant who have achieved CR, PR, and SD while on treatment.
Safety of sacituzumab govitecan with or without atezolizumab From first dose through 30 days after last treatment Adverse events (AEs) will be reported by type and grade of toxicity
Trial Locations
- Locations (1)
National Institutes of Health Clinical Center
🇺🇸Bethesda, Maryland, United States