Bladder Cancer Clinical Trial

Cisplatin and Gemcitabine Hydrochloride With or Without Berzosertib in Treating Patients With Metastatic Urothelial Cancer

Summary

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.

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Full Description

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.

View Eligibility Criteria

Eligibility Criteria

Inclusion Criteria:

Patients must have histologically or cytologically confirmed metastatic urothelial carcinoma; urothelial cancer derived from the bladder, ureter or upper tract is permitted
Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as >= 20 mm (>= 2 cm) with conventional techniques or as >= 10 mm (>= 1 cm) with spiral computed tomography (CT) scan, magnetic resonance imaging (MRI), or calipers by clinical exam
Patients must have access to archival tumor tissue for proposed correlative studies; these may be derived from transurethral resection of bladder tumors (TURBT), cystectomy, or biopsy; if archival tissue is not available for proposed correlatives, patients may be enrolled at the discretion of the study principal investigator (PI) (SKP)
No prior cytotoxic chemotherapy for metastatic disease; prior immunotherapy is permitted
At least 12 months have elapsed since platinum-based peri-operative treatment
Karnofsky >= 70% (Eastern Cooperative Oncology Group [ECOG] performance status 0-1)
Life expectancy of greater than 3 months
Leukocytes >= 3,000/mcL
Absolute neutrophil count >= 1,500/mcL
Platelets >= 100,000/mcL
Total bilirubin within institutional upper limit of normal
Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional upper limit of normal
Creatinine clearance >= 50 mL/min by either measured (using the Cockcroft-Gault, Modification of Diet in Renal Disease [MDRD] or Chronic Kidney Disease Epidemiology [CKD-EPI] formula) or calculated clearance (i.e. glomerular filtration rate [GFR])
The effects of M6620 (VX-970) on the developing human fetus are unknown; for this reason and because DNA-damage response (DDR) inhibitors as well as other therapeutic agents used in this trial may have teratogenic potential, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately; men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 6 months after completion of M6620 (VX-970) administration
Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

Radiotherapy within 4 weeks of protocol therapy
Patients who are receiving any other investigational agents
History of allergic reactions attributed to compounds of similar chemical or biologic composition to M6620 (VX970), cisplatin, or gemcitabine
M6620 (VX-970) is primarily metabolized by CYP3A4; therefore, concomitant administration with strong inhibitors or inducers of CYP3A4 should be avoided; because the lists of these agents are constantly changing, it is important to regularly consult a frequently-updated medical reference for a list of drugs to avoid or minimize use of; Patient Drug Information Handout and Wallet Card should be provided to patients; as part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product
Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
Pregnant women are excluded from this study because M6620 (VX-970) as a DNA-damage response (DDR) inhibitor may have the potential for teratogenic or abortifacient effects; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with M6620 (VX-970), breastfeeding should be discontinued if the mother is treated with M6620 (VX-970); these potential risks may also apply to other agents used in this study
Patients with >= grade 2 neuropathy

Study is for people with:

Bladder Cancer

Phase:

Phase 2

Estimated Enrollment:

87

Study ID:

NCT02567409

Recruitment Status:

Active, not recruiting

Sponsor:

National Cancer Institute (NCI)

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There are 36 Locations for this study

See Locations Near You

Mayo Clinic Hospital in Arizona
Phoenix Arizona, 85054, United States
Mayo Clinic in Arizona
Scottsdale Arizona, 85259, United States
City of Hope Comprehensive Cancer Center
Duarte California, 91010, United States
Los Angeles General Medical Center
Los Angeles California, 90033, United States
USC / Norris Comprehensive Cancer Center
Los Angeles California, 90033, United States
USC Norris Oncology/Hematology-Newport Beach
Newport Beach California, 92663, United States
Stanford Cancer Institute Palo Alto
Palo Alto California, 94304, United States
Keck Medical Center of USC Pasadena
Pasadena California, 91105, United States
University of California Davis Comprehensive Cancer Center
Sacramento California, 95817, United States
UCHealth University of Colorado Hospital
Aurora Colorado, 80045, United States
Mayo Clinic in Florida
Jacksonville Florida, 32224, United States
Emory University Hospital/Winship Cancer Institute
Atlanta Georgia, 30322, United States
University of Kansas Clinical Research Center
Fairway Kansas, 66205, United States
University of Kansas Hospital-Westwood Cancer Center
Westwood Kansas, 66205, United States
University of Kentucky/Markey Cancer Center
Lexington Kentucky, 40536, United States
Johns Hopkins University/Sidney Kimmel Cancer Center
Baltimore Maryland, 21287, United States
Massachusetts General Hospital Cancer Center
Boston Massachusetts, 02114, United States
Brigham and Women's Hospital
Boston Massachusetts, 02115, United States
Beth Israel Deaconess Medical Center
Boston Massachusetts, 02215, United States
Dana-Farber Cancer Institute
Boston Massachusetts, 02215, United States
Wayne State University/Karmanos Cancer Institute
Detroit Michigan, 48201, United States
Weisberg Cancer Treatment Center
Farmington Hills Michigan, 48334, United States
Mayo Clinic in Rochester
Rochester Minnesota, 55905, United States
Siteman Cancer Center at West County Hospital
Creve Coeur Missouri, 63141, United States
Washington University School of Medicine
Saint Louis Missouri, 63110, United States
Siteman Cancer Center-South County
Saint Louis Missouri, 63129, United States
Siteman Cancer Center at Christian Hospital
Saint Louis Missouri, 63136, United States
Nebraska Medicine-Bellevue
Bellevue Nebraska, 68123, United States
Nebraska Medicine-Village Pointe
Omaha Nebraska, 68118, United States
University of Nebraska Medical Center
Omaha Nebraska, 68198, United States
UNC Lineberger Comprehensive Cancer Center
Chapel Hill North Carolina, 27599, United States
Duke University Medical Center
Durham North Carolina, 27710, United States
Case Western Reserve University
Cleveland Ohio, 44106, United States
Ohio State University Comprehensive Cancer Center
Columbus Ohio, 43210, United States
University of Pittsburgh Cancer Institute (UPCI)
Pittsburgh Pennsylvania, 15232, United States
Vanderbilt Breast Center at One Hundred Oaks
Nashville Tennessee, 37204, United States
Vanderbilt University/Ingram Cancer Center
Nashville Tennessee, 37232, United States
University of Virginia Cancer Center
Charlottesville Virginia, 22908, United States
University of Wisconsin Carbone Cancer Center - University Hospital
Madison Wisconsin, 53792, United States

How clear is this clinincal trial information?

Study is for people with:

Bladder Cancer

Phase:

Phase 2

Estimated Enrollment:

87

Study ID:

NCT02567409

Recruitment Status:

Active, not recruiting

Sponsor:


National Cancer Institute (NCI)

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