Cisplatin and Gemcitabine Hydrochloride with or without ATR Kinase Inhibitor M6620 in Treating Patients with Metastatic Urothelial Cancer

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Status: Active

Description

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 (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. 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.

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

Locations & Contacts

Arizona

Phoenix
Mayo Clinic Hospital
Status: Active
Contact: Site Public Contact
Phone: 855-776-0015
Scottsdale
Mayo Clinic in Arizona
Status: Active
Contact: Site Public Contact
Phone: 855-776-0015

California

Duarte
City of Hope Comprehensive Cancer Center
Status: Active
Contact: Site Public Contact
Phone: 800-826-4673
Email: becomingapatient@coh.org
Los Angeles
Los Angeles County-USC Medical Center
Status: Active
Contact: Site Public Contact
Phone: 323-865-0451
USC / Norris Comprehensive Cancer Center
Status: Active
Contact: Site Public Contact
Phone: 323-865-0451
Newport Beach
USC Norris Oncology / Hematology-Newport Beach
Status: Active
Contact: Site Public Contact
Phone: 323-865-0451
Pasadena
Keck Medical Center of USC Pasadena
Status: Active
Contact: Site Public Contact
Phone: 323-865-0451
Sacramento
University of California Davis Comprehensive Cancer Center
Status: Active
Contact: Site Public Contact
Phone: 916-734-3089

Colorado

Aurora
University of Colorado Hospital
Status: Active
Contact: Site Public Contact
Phone: 720-848-0650

Florida

Jacksonville
Mayo Clinic in Florida
Status: Active
Contact: Site Public Contact
Phone: 855-776-0015

Georgia

Atlanta
Emory University Hospital / Winship Cancer Institute
Status: Active
Contact: Site Public Contact
Phone: 404-778-1868

Kansas

Fairway
University of Kansas Clinical Research Center
Status: Active
Contact: Site Public Contact
Phone: 913-945-7552
Email: ctnursenav@kumc.edu
Westwood
University of Kansas Hospital-Westwood Cancer Center
Status: Active
Contact: Site Public Contact
Phone: 913-945-7552
Email: ctnursenav@kumc.edu

Kentucky

Lexington
University of Kentucky / Markey Cancer Center
Status: Active
Contact: Site Public Contact
Phone: 859-257-3379

Maryland

Baltimore
Johns Hopkins University / Sidney Kimmel Cancer Center
Status: Active
Contact: Site Public Contact
Phone: 410-955-8804
Email: jhcccro@jhmi.edu

Massachusetts

Boston
Beth Israel Deaconess Medical Center
Status: Active
Contact: Site Public Contact
Phone: 617-667-9925
Brigham and Women's Hospital
Status: Active
Contact: Site Public Contact
Phone: 617-724-5200
Dana-Farber Cancer Institute
Status: Active
Contact: Site Public Contact
Phone: 877-442-3324
Massachusetts General Hospital Cancer Center
Status: Active
Contact: Site Public Contact
Phone: 877-726-5130

Michigan

Detroit
Wayne State University / Karmanos Cancer Institute
Status: Active
Contact: Site Public Contact
Phone: 313-576-9790
Email: ctoadmin@karmanos.org
Farmington Hills
Weisberg Cancer Treatment Center
Status: Active
Contact: Site Public Contact
Phone: 313-576-9790
Email: ctoadmin@karmanos.org

Minnesota

Rochester
Mayo Clinic
Status: Active
Contact: Site Public Contact
Phone: 855-776-0015

Nebraska

Bellevue
Nebraska Medicine-Bellevue
Status: Active
Contact: Site Public Contact
Phone: 402-559-6941
Email: unmcrsa@unmc.edu
Omaha
Nebraska Medicine-Village Pointe
Status: Active
Contact: Site Public Contact
Phone: 402-559-5600
University of Nebraska Medical Center
Status: Active
Contact: Site Public Contact
Phone: 402-559-6941
Email: unmcrsa@unmc.edu

North Carolina

Chapel Hill
UNC Lineberger Comprehensive Cancer Center
Status: Active
Contact: Site Public Contact
Phone: 877-668-0683
Email: cancerclinicaltrials@med.unc.edu
Durham
Duke University Medical Center
Status: Active
Contact: Site Public Contact
Phone: 888-275-3853

Ohio

Cleveland
Case Western Reserve University
Status: Active
Contact: Site Public Contact
Phone: 800-641-2422
Email: CTUReferral@UHhospitals.org
Columbus
Ohio State University Comprehensive Cancer Center
Status: Active
Contact: Site Public Contact
Phone: 800-293-5066
Email: Jamesline@osumc.edu

Pennsylvania

Pittsburgh
University of Pittsburgh Cancer Institute (UPCI)
Status: Active
Contact: Site Public Contact
Phone: 412-647-8073

Tennessee

Nashville
Vanderbilt Breast Center at One Hundred Oaks
Status: Active
Contact: Site Public Contact
Phone: 800-811-8480
Vanderbilt University / Ingram Cancer Center
Status: Active
Contact: Site Public Contact
Phone: 800-811-8480

Virginia

Charlottesville
University of Virginia Cancer Center
Status: Active
Contact: Site Public Contact
Phone: 434-243-6303
Email: PAS9E@virginia.edu

Wisconsin

Madison
University of Wisconsin Hospital and Clinics
Status: Active
Contact: Site Public Contact
Phone: 800-622-8922

Trial Objectives and Outline

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 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.

Trial Phase & Type

Trial Phase

Phase II

Trial Type

Treatment

Lead Organization

Lead Organization
City of Hope Comprehensive Cancer Center LAO

Principal Investigator
Sumanta Kumar Pal

Trial IDs

Primary ID 9947
Secondary IDs NCI-2015-01642, PHII-135
Clinicaltrials.gov ID NCT02567409