Trials / Recruiting
RecruitingNCT06524544
A Study Comparing the Combination of Pembrolizumab and Sacituzumab Govitecan Versus Standard of Care in the Treatment of Advanced Urothelial Cancer
A Phase III Randomized Trial of Pembrolizumab in Combination With Sacituzumab Govitecan vs Standard of Care in Anti-PD(L)1-Resistant Advanced Urothelial Cancer
- Status
- Recruiting
- Phase
- Phase 3
- Study type
- Interventional
- Enrollment
- 320 (estimated)
- Sponsor
- National Cancer Institute (NCI) · NIH
- Sex
- All
- Age
- 18 Years
- Healthy volunteers
- Not accepted
Summary
This phase III trial compares the effectiveness of pembrolizumab and sacituzumab govitecan to standard of care in treating patients with urothelial cancer that has spread to nearby tissue or lymph nodes (locally advanced) or that has spread to other places in the body (metastatic). Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Sacituzumab govitecan is a monoclonal antibody, called sacituzumab, linked to a chemotherapy drug called govitecan. Sacituzumab attaches to TROP2 positive tumor cells in a targeted way and delivers govitecan to kill them. The usual treatment approach is treatment with chemotherapy such as cisplatin, carboplatin, gemcitabine, docetaxel or paclitaxel. Cisplatin is in a class of medications known as platinum-containing compounds. It works by killing, stopping or slowing the growth of tumor cells. Carboplatin is in a class of medications known as platinum-containing compounds. It works in a way similar to the anticancer drug cisplatin, but may be better tolerated than cisplatin. Carboplatin works by killing, stopping or slowing the growth of tumor cells. Gemcitabine is a chemotherapy drug that blocks the cells from making deoxyribonucleic acid and may kill tumor cells. Docetaxel is in a class of medications called taxanes. It stops tumor cells from growing and dividing and may kill them. Paclitaxel is in a class of medications called antimicrotubule agents. It stops tumor cells from growing and dividing and may kill them. Giving pembrolizumab and sacituzumab govitecan may be more effective than usual care of carboplatin or cisplatin with gemcitabine, docetaxel or paclitaxel in treating patients with locally advanced or metastatic urothelial cancer.
Detailed description
PRIMARY OBJECTIVE: I. To compare overall survival (OS) between the therapy of physician choice (TPC) arm and the sacituzumab govitecan + pembrolizumab arm. SECONDARY OBJECTIVES: I. To compare the progression free survival (PFS) between the TPC arm and the sacituzumab govitecan + pembrolizumab arm. II. To evaluate overall response rate (ORR) between the TPC arm and the sacituzumab govitecan + pembrolizumab arm. III. To evaluate clinical benefit rate (complete response \[CR\]/partial response \[PR\] /stable disease \[SD\]) between the TPC arm and the sacituzumab govitecan + pembrolizumab arm. IV. To evaluate duration of response (DoR) between the TPC arm and the sacituzumab govitecan + pembrolizumab arm. V. To evaluate toxicity of the sacituzumab govitecan + pembrolizumab arm using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE). EXPLORATORY HEALTH RELATED QUALITY OF LIFE (HRQOL) OBJECTIVES: I. To compare HRQOL, as assessed by the National Comprehensive Cancer Network/Functional Assessment of Cancer Therapy Bladder Symptom Index-18 (FBISI-18) summary score between patients on the TPC arm versus the sacituzumab govitecan + pembrolizumab arm at 6 months. II. To compare HRQOL change from baseline, as assessed by the FBISI-18 summary score, for patients on the TPC arm versus the sacituzumab govitecan + pembrolizumab arm at baseline, 3, 6, and 12 months. III. To compare the change in patient-reported fatigue from baseline and across 3, 6, and 12 months as measured by the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) summary score; change from baseline will be compared between patients on the TPC arm versus the sacituzumab govitecan + pembrolizumab arm. IV. To compare quality-adjusted survival (overall survival x health utility score assessed by the European Quality of Life Five Dimension Five Level \[EQ-5D-5L\]) between patients on the TPC arm versus the sacituzumab govitecan + pembrolizumab arm. V. To compare time to HRQOL deterioration in global HRQOL, as measured by the FBISI-18 disease-related physical symptom subscale (FBISI-18 disease-related symptoms (DRS) in the physical emotional domains \[DRS-P\]), between patients on the TPC arm versus the sacituzumab govitecan + pembrolizumab arm. OUTLINE: Patients are randomized to 1 of 2 arms. ARM A: Patients receive TPC with carboplatin or cisplatin intravenously (IV) on day 1 and gemcitabine IV on days 1 and 8 of each cycle. Cycles repeat every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients may alternately receive TPC with docetaxel IV on day 1 of each cycle or paclitaxel IV on days 1 and 8 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients additionally undergo blood sample collection and computed tomography (CT) or magnetic resonance imaging (MRI) throughout the study. ARM B: Patients receive sacituzumab govitecan IV over 1-3 hours on days 1 and 8 and pembrolizumab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 21 days for up to 35 cycles or for 2 years of pembrolizumab in the absence of disease progression or unacceptable toxicity. Cycles of sacituzumab govitecan repeats every 21 days in the absence of disease progression or unacceptable toxicity. Patients additional undergo blood sample collection, and CT or MRI throughout the study. After completion of study treatment, patients are followed up at 30 days then once a year for 5 years from the date of randomization.
Conditions
- Locally Advanced Urothelial Carcinoma
- Metastatic Urothelial Carcinoma
- Unresectable Urothelial Carcinoma
Interventions
| Type | Name | Description |
|---|---|---|
| PROCEDURE | Biospecimen Collection | Undergo blood sample collection |
| DRUG | Carboplatin | Given IV |
| DRUG | Cisplatin | Given IV |
| PROCEDURE | Computed Tomography | Undergo CT |
| DRUG | Docetaxel | Given IV |
| DRUG | Gemcitabine | Given IV |
| PROCEDURE | Magnetic Resonance Imaging | Undergo MRI |
| DRUG | Paclitaxel | Given IV |
| BIOLOGICAL | Pembrolizumab | Given IV |
| OTHER | Questionnaire Administration | Ancillary studies |
| BIOLOGICAL | Sacituzumab Govitecan | Given IV |
Timeline
- Start date
- 2025-12-02
- Primary completion
- 2028-12-31
- Completion
- 2028-12-31
- First posted
- 2024-07-29
- Last updated
- 2026-04-15
Locations
114 sites across 1 country: United States
Regulatory
- FDA-regulated drug study
Source: ClinicalTrials.gov record NCT06524544. Inclusion in this directory is not an endorsement.