Clinical Trial - NCT02567409

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

Recruiting

Sponsor: National Cancer Institute (NCI)

Collaborators:

Information provided by (Responsible party): Sponsor

ClinicalTrials.gov Identifier: NCT02567409

Protocol Info

Short Description: Cisplatin and Gemcitabine Hydrochloride With or Without ATR Kinase Inhibitor VX-970 in Treating Patients With Metastatic Urothelial Cancer
Long Description: A Randomized Phase 2 Trial of Cisplatin/Gemcitabine with or without VX-970 in Metastatic Urothelial Carcinoma
MGH Status: Open
Sponsor: NCI
Disease Program: GU

Next Steps


If you are interested in this protocol or in other treatment options at Massachusetts General Hospital, please Request a Consultation.




Purpose

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 Title Intervention Phase
Metastatic Urothelial Carcinoma of the Renal Pelvis and Ureter Stage IV Bladder Urothelial Carcinoma AJCC v7 ATR Kinase Inhibitor M6620 Cisplatin Gemcitabine Hydrochloride Laboratory Biomarker Analysis Pharmacological Study Phase 2
Study Type Interventional
Official Title A Randomized Phase 2 Trial of Cisplatin/Gemcitabine With or Without M6620 (VX-970) in Metastatic Urothelial Carcinoma

Primary Outcome Measures

Progression-free survival (PFS) [Time Frame: Day of randomization, until progression, death, or the start of another treatment, assessed up to 12 months] [Designated as safety issue: ]


Secondary Outcome Measures

Overall survival (OS) [Time Frame: Up to 36 months] [Designated as safety issue: ]

Overall response rate assessed by the Response Evaluation Criteria in Solid Tumors version 1.1 [Time Frame: Up to 36 months] [Designated as safety issue: ]

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] [Designated as safety issue: ]

Analysis of potential predictors of response (including p53, p21, and ERCC2 mutations) [Time Frame: Up to 36 months] [Designated as safety issue: ]

Estimated Enrollment: 90
Study Start Date: August 2016
Estimated Study Completion Date:
Estimated Primary Completion Date: August 2019
Arms Assigned Interventions

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.
Other:Pharmacological Study
Correlative studies

Experimental:Arm B (gemcitabine hydrochloride, cisplatin)

Patients receive gemcitabine hydrochloride and cisplatin as in Arm A.

Eligibility

Ages Eligible for Study: N/A-N/A

Genders Eligible for Study: All

Accepts Healthly Volunteers: No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT02567409

Locations

  • United States, Arizona
    • Mayo Clinic Hospital Phoenix, Arizona, United States, 85054
    • Mayo Clinic in Arizona Scottsdale, Arizona, United States, 85259
  • United States, California
    • City of Hope Comprehensive Cancer Center Duarte, California, United States, 91010
    • Los Angeles County-USC Medical Center Los Angeles, California, United States, 90033
    • USC / Norris Comprehensive Cancer Center Los Angeles, California, United States, 90033
    • USC Norris Oncology/Hematology-Newport Beach Newport Beach, California, United States, 92663
    • Stanford Cancer Institute Palo Alto Palo Alto, California, United States, 94304
    • Keck Medical Center of USC Pasadena Pasadena, California, United States, 91105
    • University of California Davis Comprehensive Cancer Center Sacramento, California, United States, 95817
  • United States, Colorado
    • University of Colorado Hospital Aurora, Colorado, United States, 80045
  • United States, Florida
    • Mayo Clinic in Florida Jacksonville, Florida, United States, 32224-9980
  • United States, Georgia
    • Emory University Hospital/Winship Cancer Institute Atlanta, Georgia, United States, 30322
  • United States, Kansas
    • University of Kansas Clinical Research Center Fairway, Kansas, United States, 66205
    • University of Kansas Hospital-Westwood Cancer Center Westwood, Kansas, United States, 66205
  • United States, Kentucky
    • University of Kentucky/Markey Cancer Center Lexington, Kentucky, United States, 40536
  • United States, Maryland
    • Johns Hopkins University/Sidney Kimmel Cancer Center Baltimore, Maryland, United States, 21287
  • United States, Massachusetts
    • Massachusetts General Hospital Cancer Center Boston, Massachusetts, United States, 02114
    • Brigham and Women's Hospital Boston, Massachusetts, United States, 02115
    • Beth Israel Deaconess Medical Center Boston, Massachusetts, United States, 02215
    • Dana-Farber Cancer Institute Boston, Massachusetts, United States, 02215
  • United States, Michigan
    • Wayne State University/Karmanos Cancer Institute Detroit, Michigan, United States, 48201
    • Weisberg Cancer Treatment Center Farmington Hills, Michigan, United States, 48334
  • United States, Minnesota
    • Mayo Clinic Rochester, Minnesota, United States, 55905
  • United States, Missouri
    • Siteman Cancer Center at West County Hospital Creve Coeur, Missouri, United States, 63141
    • Washington University School of Medicine Saint Louis, Missouri, United States, 63110
    • Siteman Cancer Center-South County Saint Louis, Missouri, United States, 63129
    • Siteman Cancer Center at Christian Hospital Saint Louis, Missouri, United States, 63136
  • United States, North Carolina
    • UNC Lineberger Comprehensive Cancer Center Chapel Hill, North Carolina, United States, 27599
    • Duke University Medical Center Durham, North Carolina, United States, 27710
  • United States, Ohio
    • Case Western Reserve University Cleveland, Ohio, United States, 44106
    • Ohio State University Comprehensive Cancer Center Columbus, Ohio, United States, 43210
  • United States, Pennsylvania
    • University of Pittsburgh Cancer Institute (UPCI) Pittsburgh, Pennsylvania, United States, 15232
  • United States, Tennessee
    • Vanderbilt University/Ingram Cancer Center Nashville, Tennessee, United States, 37232
  • United States, Virginia
    • University of Virginia Cancer Center Charlottesville, Virginia, United States, 22908
  • United States, Wisconsin
    • University of Wisconsin Hospital and Clinics Madison, Wisconsin, United States, 53792

Sponsors and Collaborators

National Cancer Institute (NCI)

More Information

No publications provided

Responsible Party: Sponsor
ClinicalTrials.gov Identifier: NCT02567409
Other Study ID Numbers: NCI-2015-01642
Study First Received:
Last Updated:
Health Authority:

Additional relevant MeSH terms:

Carcinoma

Carcinoma, Transitional Cell

Kidney Neoplasms

Ureteral Neoplasms

Cisplatin

Gemcitabine

Next Steps


If you are interested in this protocol or in other treatment options at Massachusetts General Hospital, please Request a Consultation.







ClinicalTrials.gov processed this data on May 30, 2019