This phase II trial studies how well cisplatin and gemcitabine hydrochloride with or without berzosertib works in treating patients with urothelial cancer that has spread to other places in the body (metastatic). Drugs used in chemotherapy, such as cisplatin and gemcitabine hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Berzosertib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known if cisplatin and gemcitabine hydrochloride work better alone or with berzosertib in treating patients with urothelial cancer.
PRIMARY OBJECTIVE: I. To determine if the addition of berzosertib (M6620 \[VX-970\]) to cisplatin/gemcitabine hydrochloride (gemcitabine) improves progression-free survival (PFS) relative to cisplatin/gemcitabine alone. SECONDARY OBJECTIVES: I. To compare overall survival (OS) with the addition of M6620 (VX-970) to cisplatin/gemcitabine relative to cisplatin/gemcitabine alone. II. To compare tumor response rate with the addition of M6620 (VX-970) to cisplatin/gemcitabine relative to cisplatin/gemcitabine alone. III. To compare safety with the addition of M6620 (VX-970) to cisplatin/gemcitabine relative to cisplatin/gemcitabine alone. IV. To assess the role of p53 status in predicting response to M6620 (VX-970)-based therapy. OUTLINE: Patients are randomized to 1 of 2 arms. ARM A: Patients receive gemcitabine hydrochloride intravenously (IV) over 30 minutes on days 1 and 8, and cisplatin IV over 60 minutes on day 1. Patients also receive berzosertib IV over 60 minutes on days 2 and 9. Treatment repeats every 21 days for 6 cycles in the absence of disease progression or unacceptable toxicity. ARM B: Patients receive gemcitabine hydrochloride and cisplatin as in Arm A. After completion of study treatment, patients are followed up to 36 months.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
87
Mayo Clinic Hospital in Arizona
Phoenix, Arizona, United States
Mayo Clinic in Arizona
Scottsdale, Arizona, United States
City of Hope Comprehensive Cancer Center
Duarte, California, United States
Los Angeles General Medical Center
Los Angeles, California, United States
USC / Norris Comprehensive Cancer Center
Los Angeles, California, United States
Progression-free Survival (PFS)
Estimated using the product-limit method of Kaplan and Meier. Event defined as progression or death from any cause. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
Time frame: Day of randomization, until progression, or death, assessed up to 12 months
Overall Survival (OS)
Estimated using the product-limit method of Kaplan and Meier. Event defined as death from any cause.
Time frame: Up to 36 months
Confirmed Objective Response Rate
Response was assessed using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Confirmed Objective Response = CR + PR.
Time frame: Up to 36 months
Treatment Limiting Adverse Events
Adverse events that were fatal or led to treatment discontinuation.
Time frame: Assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 36 months.
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
USC Norris Oncology/Hematology-Newport Beach
Newport Beach, California, United States
Stanford Cancer Institute Palo Alto
Palo Alto, California, United States
Keck Medical Center of USC Pasadena
Pasadena, California, United States
University of California Davis Comprehensive Cancer Center
Sacramento, California, United States
UCHealth University of Colorado Hospital
Aurora, Colorado, United States
...and 29 more locations