- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02567409
Cisplatin and Gemcitabine Hydrochloride With or Without Berzosertib in Treating Patients With Metastatic Urothelial Cancer
A Randomized Phase 2 Trial of Cisplatin/Gemcitabine With or Without M6620 (VX-970) in Metastatic Urothelial Carcinoma
Study Overview
Status
Conditions
Intervention / Treatment
Detailed 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.
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
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Arizona
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Phoenix, Arizona, United States, 85054
- Mayo Clinic Hospital in Arizona
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Scottsdale, Arizona, United States, 85259
- Mayo Clinic in Arizona
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California
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Duarte, California, United States, 91010
- City of Hope Comprehensive Cancer Center
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Los Angeles, California, United States, 90033
- USC / Norris Comprehensive Cancer Center
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Los Angeles, California, United States, 90033
- Los Angeles General Medical Center
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Newport Beach, California, United States, 92663
- USC Norris Oncology/Hematology-Newport Beach
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Palo Alto, California, United States, 94304
- Stanford Cancer Institute Palo Alto
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Pasadena, California, United States, 91105
- Keck Medical Center of USC Pasadena
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Sacramento, California, United States, 95817
- University of California Davis Comprehensive Cancer Center
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Colorado
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Aurora, Colorado, United States, 80045
- UCHealth University of Colorado Hospital
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Florida
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Jacksonville, Florida, United States, 32224-9980
- Mayo Clinic in Florida
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Georgia
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Atlanta, Georgia, United States, 30322
- Emory University Hospital/Winship Cancer Institute
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Kansas
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Fairway, Kansas, United States, 66205
- University of Kansas Clinical Research Center
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Westwood, Kansas, United States, 66205
- University of Kansas Hospital-Westwood Cancer Center
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Kentucky
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Lexington, Kentucky, United States, 40536
- University of Kentucky/Markey Cancer Center
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Maryland
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Baltimore, Maryland, United States, 21287
- Johns Hopkins University/Sidney Kimmel Cancer Center
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Massachusetts
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Boston, Massachusetts, United States, 02215
- Beth Israel Deaconess Medical Center
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Boston, Massachusetts, United States, 02215
- Dana-Farber Cancer Institute
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Boston, Massachusetts, United States, 02115
- Brigham and Women's Hospital
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Boston, Massachusetts, United States, 02114
- Massachusetts General Hospital Cancer Center
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Michigan
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Detroit, Michigan, United States, 48201
- Wayne State University/Karmanos Cancer Institute
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Farmington Hills, Michigan, United States, 48334
- Weisberg Cancer Treatment Center
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Minnesota
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Rochester, Minnesota, United States, 55905
- Mayo Clinic in Rochester
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Missouri
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Creve Coeur, Missouri, United States, 63141
- Siteman Cancer Center at West County Hospital
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Saint Louis, Missouri, United States, 63110
- Washington University School of Medicine
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Saint Louis, Missouri, United States, 63129
- Siteman Cancer Center-South County
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Saint Louis, Missouri, United States, 63136
- Siteman Cancer Center at Christian Hospital
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Nebraska
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Bellevue, Nebraska, United States, 68123
- Nebraska Medicine-Bellevue
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Omaha, Nebraska, United States, 68198
- University of Nebraska Medical Center
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Omaha, Nebraska, United States, 68118
- Nebraska Medicine-Village Pointe
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North Carolina
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Chapel Hill, North Carolina, United States, 27599
- UNC Lineberger Comprehensive Cancer Center
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Durham, North Carolina, United States, 27710
- Duke University Medical Center
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Ohio
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Cleveland, Ohio, United States, 44106
- Case Western Reserve University
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Columbus, Ohio, United States, 43210
- Ohio State University Comprehensive Cancer Center
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Pennsylvania
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Pittsburgh, Pennsylvania, United States, 15232
- University of Pittsburgh Cancer Institute (UPCI)
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Tennessee
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Nashville, Tennessee, United States, 37232
- Vanderbilt University/Ingram Cancer Center
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Nashville, Tennessee, United States, 37204
- Vanderbilt Breast Center at One Hundred Oaks
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Virginia
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Charlottesville, Virginia, United States, 22908
- University of Virginia Cancer Center
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Wisconsin
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Madison, Wisconsin, United States, 53792
- University of Wisconsin Carbone Cancer Center
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
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 Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Arm A (berzosertib, gemcitabine hydrochloride, cisplatin)
Patients receive gemcitabine hydrochloride 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.
|
Given IV
Other Names:
Given IV
Other Names:
Given IV
Other Names:
|
Experimental: Arm B (gemcitabine hydrochloride, cisplatin)
Patients receive gemcitabine hydrochloride and cisplatin as in Arm A.
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Given IV
Other Names:
Given IV
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Progression-free Survival (PFS)
Time Frame: Day of randomization, until progression, or death, assessed up to 12 months
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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.
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Day of randomization, until progression, or death, assessed up to 12 months
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Overall Survival (OS)
Time Frame: Up to 36 months
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Estimated using the product-limit method of Kaplan and Meier.
Event defined as death from any cause.
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Up to 36 months
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Confirmed Objective Response Rate
Time Frame: Up to 36 months
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Response was assessed using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
Confirmed Objective Response = CR + PR.
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Up to 36 months
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Treatment Limiting Adverse Events
Time Frame: Assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 36 months.
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Adverse events that were fatal or led to treatment discontinuation.
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Assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 36 months.
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Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Sumanta K Pal, City of Hope Comprehensive Cancer Center LAO
Publications and helpful links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimated)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- NCI-2015-01642 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
- UM1CA186690 (U.S. NIH Grant/Contract)
- UM1CA186717 (U.S. NIH Grant/Contract)
- PHII-135
- 9947 (Other Identifier: CTEP)
- N01CM00038 (U.S. NIH Grant/Contract)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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