Sacituzumab Govitecan With or Without Atezolizumab Immunotherapy in Rare Genitourinary Tumors (SMART) Such as Small Cell, Adenocarcinoma, and Squamous Cell Bladder/Urinary Tract Cancer, Renal Medullary Carcinoma and Penile Cancer

Renal Medullary Carcinoma Clinical Trial

Official title: A Phase II Study of Sacituzumab Govitecan With or Without Atezolizumab Immunotherapy in Rare Genitourinary Tumors (SMART) Such as Small Cell, Adenocarcinoma, and Squamous Cell Bladder/Urinary Tract Cancer, Renal Medullary Carcinoma and Penile Cancer

Status Not yet recruiting

Clinical Trial 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 small cell carcinoma of the bladder; 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.

Clinical Trial 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 small cell carcinoma, 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: small cell carcinoma, 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. ;

Related Conditions & MeSH terms

• Adenocarcinoma
• Carcinoma
• Carcinoma, Neuroendocrine
• Carcinoma, Small Cell
• Carcinoma, Squamous Cell
• Kidney Neoplasms
• Penile Neoplasms
• Renal Medullary Carcinoma
• Small Cell Lung Carcinoma
• Squamous Cell Carcinoma of the Bladder
• Squamous Cell Carcinoma of the Penis
• Thyroid Neoplasms
• Urinary Bladder Neoplasms
• Urologic Neoplasms

• NCT number: NCT06161532
• Study type: Interventional
• Source: National Institutes of Health Clinical Center (CC)
• Contact: Lisa Ley, R.N.
• Phone: (240) 858-3524
• Email: lisa.ley@nih.gov
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: June 26, 2024
• Completion date: November 1, 2028