Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

Cisplatin and Gemcitabine Hydrochloride With or Without ATR Kinase Inhibitor M6620 in Treating Patients With Metastatic Urothelial Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02567409
Recruitment Status : Recruiting
First Posted : October 5, 2015
Last Update Posted : March 21, 2019
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Brief Summary:
This randomized phase II trial studies how well cisplatin and gemcitabine hydrochloride with or without ATR kinase inhibitor M6620 works in treating patients with urothelial cancer that has spread to other places in the body. 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. ATR kinase inhibitor M6620 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 ATR kinase inhibitor M6620 in treating patients with urothelial cancer.

Condition or disease Intervention/treatment Phase
Metastatic Urothelial Carcinoma of the Renal Pelvis and Ureter Stage IV Bladder Urothelial Carcinoma AJCC v7 Drug: ATR Kinase Inhibitor M6620 Drug: Cisplatin Drug: Gemcitabine Hydrochloride Other: Laboratory Biomarker Analysis Other: Pharmacological Study Phase 2

Detailed Description:

PRIMARY OBJECTIVES:

I. To determine if the addition of ATR kinase inhibitor M6620 (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 ATR kinase inhibitor M6620 IV over 60 minutes on days 2 and 9. Treatment repeats every 21 days for 6 courses 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.


Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 90 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Randomized Phase 2 Trial of Cisplatin/Gemcitabine With or Without M6620 (VX-970) in Metastatic Urothelial Carcinoma
Actual Study Start Date : August 19, 2016
Estimated Primary Completion Date : August 31, 2019


Arm Intervention/treatment
Experimental: Arm A (M6620, 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 ATR kinase inhibitor M6620 IV over 60 minutes on days 2 and 9. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity.
Drug: ATR Kinase Inhibitor M6620
Given IV
Other Names:
  • M 6620
  • M6620
  • VX-970

Drug: Cisplatin
Given IV
Other Names:
  • Abiplatin
  • Blastolem
  • Briplatin
  • CDDP
  • Cis-diammine-dichloroplatinum
  • Cis-diamminedichloridoplatinum
  • Cis-diamminedichloro Platinum (II)
  • Cis-diamminedichloroplatinum
  • Cis-dichloroammine Platinum (II)
  • Cis-platinous Diamine Dichloride
  • Cis-platinum
  • Cis-platinum II
  • Cis-platinum II Diamine Dichloride
  • Cismaplat
  • Cisplatina
  • Cisplatinum
  • Cisplatyl
  • Citoplatino
  • Citosin
  • Cysplatyna
  • DDP
  • Lederplatin
  • Metaplatin
  • Neoplatin
  • Peyrone's Chloride
  • Peyrone's Salt
  • Placis
  • Plastistil
  • Platamine
  • Platiblastin
  • Platiblastin-S
  • Platinex
  • Platinol
  • Platinol- AQ
  • Platinol-AQ
  • Platinol-AQ VHA Plus
  • Platinoxan
  • Platinum
  • Platinum Diamminodichloride
  • Platiran
  • Platistin
  • Platosin

Drug: Gemcitabine Hydrochloride
Given IV
Other Names:
  • dFdCyd
  • Difluorodeoxycytidine Hydrochloride
  • Gemzar
  • LY-188011
  • LY188011

Other: Laboratory Biomarker Analysis
Correlative studies

Other: Pharmacological Study
Correlative studies

Experimental: Arm B (gemcitabine hydrochloride, cisplatin)
Patients receive gemcitabine hydrochloride and cisplatin as in Arm A.
Drug: Cisplatin
Given IV
Other Names:
  • Abiplatin
  • Blastolem
  • Briplatin
  • CDDP
  • Cis-diammine-dichloroplatinum
  • Cis-diamminedichloridoplatinum
  • Cis-diamminedichloro Platinum (II)
  • Cis-diamminedichloroplatinum
  • Cis-dichloroammine Platinum (II)
  • Cis-platinous Diamine Dichloride
  • Cis-platinum
  • Cis-platinum II
  • Cis-platinum II Diamine Dichloride
  • Cismaplat
  • Cisplatina
  • Cisplatinum
  • Cisplatyl
  • Citoplatino
  • Citosin
  • Cysplatyna
  • DDP
  • Lederplatin
  • Metaplatin
  • Neoplatin
  • Peyrone's Chloride
  • Peyrone's Salt
  • Placis
  • Plastistil
  • Platamine
  • Platiblastin
  • Platiblastin-S
  • Platinex
  • Platinol
  • Platinol- AQ
  • Platinol-AQ
  • Platinol-AQ VHA Plus
  • Platinoxan
  • Platinum
  • Platinum Diamminodichloride
  • Platiran
  • Platistin
  • Platosin

Drug: Gemcitabine Hydrochloride
Given IV
Other Names:
  • dFdCyd
  • Difluorodeoxycytidine Hydrochloride
  • Gemzar
  • LY-188011
  • LY188011

Other: Laboratory Biomarker Analysis
Correlative studies

Other: Pharmacological Study
Correlative studies




Primary Outcome Measures :
  1. Progression-free survival (PFS) [ Time Frame: Day of randomization, until progression, death, or the start of another treatment, assessed up to 12 months ]
    PFS for each arm will be summarized with a Kaplan-Meier plot and 95% confidence intervals (at 3, 6, 9, and 12 months); the one-sided 0.10-level logrank test will be used to compare the two arms.


Secondary Outcome Measures :
  1. Overall survival (OS) [ Time Frame: Up to 36 months ]
    OS for each arm will be summarized with a Kaplan-Meier plot and 95% confidence intervals; the one-sided 0.10-level logrank test will be used to compare the two arms.

  2. Overall response rate assessed by the Response Evaluation Criteria in Solid Tumors version 1.1 [ Time Frame: Up to 36 months ]
    The overall response rate will be calculated as the ratio of the number of eligible randomized patients who experienced a confirmed complete response or partial response divided by the total number of randomized eligible patients who began treatment; 95% confidence intervals will be constructed. Pearson chi-square test will be used to compare the two arms in terms of the overall response rate.

  3. Incidence of toxicity graded according the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 (CTCAE version 5.0 will be utilized for adverse event reporting beginning April 1, 2018) [ Time Frame: Up to 36 months ]
    All observed toxicities will be summarized in terms of type, severity, and time of onset. Tables will be created to summarize these toxicities and side effects, overall by arm and by course. Proportions and associated 95% confidence intervals will be calculated for each arm separately and if indicated, for the difference between the arms. The two treatment arms will be compared using Fisher's exact test when presence of toxicities are dichotomized and by the Cochran-Armitage test for trend if all grades are considered.

  4. Analysis of potential predictors of response (including p53, p21, and ERCC2 mutations) [ Time Frame: Up to 36 months ]
    Archival tumor tissue will be analyzed for the presence of p53, p21, and ERCC2 mutations. For each treatment arm separately and for each of the 3 indicators (one each for presence of p53, p21, and ERCC2 mutations), the hazard ratio will be used to quantify the overall association between that gene and PFS. The Cox proportional hazards model will be used to estimate the interactions between the genes and PFS as well as the interaction between the treatment arm and each of the genes.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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])
  • 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
  • Concomitant administration with strong inhibitors or inducers of CYP3A4 should be avoided; it is important to regularly consult a frequently-updated medical reference for a list of drugs to avoid or minimize use of
  • 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; breastfeeding should be discontinued if the mother is treated with M6620 (VX970); these potential risks may also apply to other agents used in this study
  • Patients with >= grade 2 neuropathy

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02567409


  Hide Study Locations
Locations
Layout table for location information
United States, Arizona
Mayo Clinic Hospital Recruiting
Phoenix, Arizona, United States, 85054
Contact: Site Public Contact    855-776-0015      
Principal Investigator: Parminder Singh         
Mayo Clinic in Arizona Recruiting
Scottsdale, Arizona, United States, 85259
Contact: Site Public Contact    855-776-0015      
Principal Investigator: Parminder Singh         
United States, California
City of Hope Comprehensive Cancer Center Recruiting
Duarte, California, United States, 91010
Contact: Site Public Contact    800-826-4673    becomingapatient@coh.org   
Principal Investigator: Sumanta K. Pal         
Los Angeles County-USC Medical Center Recruiting
Los Angeles, California, United States, 90033
Contact: Site Public Contact    323-865-0451      
Principal Investigator: Sarmad Sadeghi         
USC / Norris Comprehensive Cancer Center Recruiting
Los Angeles, California, United States, 90033
Contact: Site Public Contact    323-865-0451      
Principal Investigator: Sarmad Sadeghi         
USC Norris Oncology/Hematology-Newport Beach Recruiting
Newport Beach, California, United States, 92663
Contact: Site Public Contact    323-865-0451      
Principal Investigator: Sarmad Sadeghi         
Stanford Cancer Institute Palo Alto Active, not recruiting
Palo Alto, California, United States, 94304
Keck Medical Center of USC Pasadena Recruiting
Pasadena, California, United States, 91105
Contact: Site Public Contact    323-865-0451      
Principal Investigator: Sarmad Sadeghi         
University of California Davis Comprehensive Cancer Center Recruiting
Sacramento, California, United States, 95817
Contact: Site Public Contact    916-734-3089      
Principal Investigator: Primo N. Lara         
United States, Colorado
University of Colorado Hospital Recruiting
Aurora, Colorado, United States, 80045
Contact: Site Public Contact    720-848-0650      
Principal Investigator: Thomas W. Flaig         
United States, Florida
Mayo Clinic in Florida Recruiting
Jacksonville, Florida, United States, 32224-9980
Contact: Site Public Contact    855-776-0015      
Principal Investigator: Parminder Singh         
United States, Georgia
Emory University Hospital/Winship Cancer Institute Recruiting
Atlanta, Georgia, United States, 30322
Contact: Site Public Contact    404-778-1868      
Principal Investigator: Bradley C. Carthon         
United States, Kansas
University of Kansas Clinical Research Center Recruiting
Fairway, Kansas, United States, 66205
Contact: Site Public Contact    913-945-7552    ctnursenav@kumc.edu   
Principal Investigator: Rahul A. Parikh         
University of Kansas Hospital-Westwood Cancer Center Recruiting
Westwood, Kansas, United States, 66205
Contact: Site Public Contact    913-945-7552    ctnursenav@kumc.edu   
Principal Investigator: Rahul A. Parikh         
United States, Kentucky
University of Kentucky/Markey Cancer Center Recruiting
Lexington, Kentucky, United States, 40536
Contact: Site Public Contact    859-257-3379      
Principal Investigator: Peng Wang         
United States, Maryland
Johns Hopkins University/Sidney Kimmel Cancer Center Recruiting
Baltimore, Maryland, United States, 21287
Contact: Site Public Contact    410-955-8804    jhcccro@jhmi.edu   
Principal Investigator: Noah M. Hahn         
United States, Massachusetts
Massachusetts General Hospital Cancer Center Recruiting
Boston, Massachusetts, United States, 02114
Contact: Site Public Contact    877-726-5130      
Principal Investigator: Philip J. Saylor         
Brigham and Women's Hospital Recruiting
Boston, Massachusetts, United States, 02115
Contact: Site Public Contact    888-823-5923    ctsucontact@westat.com   
Principal Investigator: Philip J. Saylor         
Beth Israel Deaconess Medical Center Recruiting
Boston, Massachusetts, United States, 02215
Contact: Site Public Contact    617-667-9925      
Principal Investigator: Philip J. Saylor         
Dana-Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02215
Contact: Site Public Contact    877-442-3324      
Principal Investigator: Philip J. Saylor         
United States, Michigan
Wayne State University/Karmanos Cancer Institute Recruiting
Detroit, Michigan, United States, 48201
Contact: Site Public Contact    313-576-9790    ctoadmin@karmanos.org   
Principal Investigator: Ulka N. Vaishampayan         
Weisberg Cancer Treatment Center Recruiting
Farmington Hills, Michigan, United States, 48334
Contact: Site Public Contact    313-576-9790    ctoadmin@karmanos.org   
Principal Investigator: Ulka N. Vaishampayan         
United States, Minnesota
Mayo Clinic Recruiting
Rochester, Minnesota, United States, 55905
Contact: Site Public Contact    855-776-0015      
Principal Investigator: Parminder Singh         
United States, Missouri
Siteman Cancer Center at West County Hospital Active, not recruiting
Creve Coeur, Missouri, United States, 63141
Washington University School of Medicine Active, not recruiting
Saint Louis, Missouri, United States, 63110
Siteman Cancer Center-South County Active, not recruiting
Saint Louis, Missouri, United States, 63129
Siteman Cancer Center at Christian Hospital Active, not recruiting
Saint Louis, Missouri, United States, 63136
United States, North Carolina
UNC Lineberger Comprehensive Cancer Center Recruiting
Chapel Hill, North Carolina, United States, 27599
Contact: Site Public Contact    877-668-0683    cancerclinicaltrials@med.unc.edu   
Principal Investigator: Matthew I. Milowsky         
Duke University Medical Center Recruiting
Durham, North Carolina, United States, 27710
Contact: Site Public Contact    888-275-3853      
Principal Investigator: James L. Abbruzzese         
United States, Ohio
Case Western Reserve University Recruiting
Cleveland, Ohio, United States, 44106
Contact: Site Public Contact    800-641-2422    CTUReferral@UHhospitals.org   
Principal Investigator: Christopher J. Hoimes         
Ohio State University Comprehensive Cancer Center Recruiting
Columbus, Ohio, United States, 43210
Contact: Site Public Contact    800-293-5066    Jamesline@osumc.edu   
Principal Investigator: Amir Mortazavi         
United States, Pennsylvania
University of Pittsburgh Cancer Institute (UPCI) Recruiting
Pittsburgh, Pennsylvania, United States, 15232
Contact: Site Public Contact    412-647-8073      
Principal Investigator: Leonard J. Appleman         
United States, Tennessee
Vanderbilt University/Ingram Cancer Center Recruiting
Nashville, Tennessee, United States, 37232
Contact: Site Public Contact    800-811-8480      
Principal Investigator: Nancy B. Davis         
United States, Virginia
University of Virginia Cancer Center Recruiting
Charlottesville, Virginia, United States, 22908
Contact: Site Public Contact    434-243-6303    PAS9E@virginia.edu   
Principal Investigator: Robert Dreicer         
United States, Wisconsin
University of Wisconsin Hospital and Clinics Recruiting
Madison, Wisconsin, United States, 53792
Contact: Site Public Contact    800-622-8922      
Principal Investigator: Hamid Emamekhoo         
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
Layout table for investigator information
Principal Investigator: Sumanta K Pal City of Hope Comprehensive Cancer Center LAO

Layout table for additonal information
Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT02567409     History of Changes
Other Study ID Numbers: NCI-2015-01642
NCI-2015-01642 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
PHII-135
9947 ( Other Identifier: City of Hope Comprehensive Cancer Center LAO )
9947 ( Other Identifier: CTEP )
N01CM00038 ( U.S. NIH Grant/Contract )
UM1CA186690 ( U.S. NIH Grant/Contract )
UM1CA186717 ( U.S. NIH Grant/Contract )
First Posted: October 5, 2015    Key Record Dates
Last Update Posted: March 21, 2019
Last Verified: February 2019

Additional relevant MeSH terms:
Layout table for MeSH terms
Carcinoma
Carcinoma, Transitional Cell
Kidney Neoplasms
Ureteral Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Kidney Diseases
Urologic Diseases
Ureteral Diseases
Cisplatin
Gemcitabine
Antineoplastic Agents
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs