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.
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.
Overal Status | Start Date | Phase | Study Type |
---|---|---|---|
Recruiting | August 19, 2016 | Phase 2 | Interventional |
Primary Outcome 1 - Measure: Progression-free survival (PFS)
Primary Outcome 1 - Time Frame: Day of randomization, until progression, death, or the start of another treatment, assessed up to 12 months
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
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Gender: All
Minimum Age: 18 Years
Maximum Age: N/A
Healthy Volunteers: No
Name: Sumanta K Pal
Role: Principal Investigator
Affiliation: City of Hope Comprehensive Cancer Center LAO
Facility | Status | Contact |
---|---|---|
Mayo Clinic Hospital Phoenix, Arizona 85054 United States |
Recruiting |
Site Public Contact 855-776-0015 |
Mayo Clinic in Arizona Scottsdale, Arizona 85259 United States |
Recruiting |
Site Public Contact 855-776-0015 |
City of Hope Comprehensive Cancer Center Duarte, California 91010 United States |
Recruiting |
Site Public Contact 800-826-4673 becomingapatient@coh.org |
Los Angeles County-USC Medical Center Los Angeles, California 90033 United States |
Recruiting |
Site Public Contact 323-865-0451 |
USC / Norris Comprehensive Cancer Center Los Angeles, California 90033 United States |
Recruiting |
Site Public Contact 323-865-0451 |
USC Norris Oncology/Hematology-Newport Beach Newport Beach, California 92663 United States |
Recruiting |
Site Public Contact 323-865-0451 |
Stanford Cancer Institute Palo Alto Palo Alto, California 94304 United States |
Active, not recruiting | |
Keck Medical Center of USC Pasadena Pasadena, California 91105 United States |
Recruiting |
Site Public Contact 323-865-0451 |
University of California Davis Comprehensive Cancer Center Sacramento, California 95817 United States |
Recruiting |
Site Public Contact 916-734-3089 |
University of Colorado Hospital Aurora, Colorado 80045 United States |
Recruiting |
Site Public Contact 720-848-0650 |
Mayo Clinic in Florida Jacksonville, Florida 32224-9980 United States |
Recruiting |
Site Public Contact 855-776-0015 |
Emory University Hospital/Winship Cancer Institute Atlanta, Georgia 30322 United States |
Recruiting |
Site Public Contact 404-778-1868 |
University of Kansas Clinical Research Center Fairway, Kansas 66205 United States |
Recruiting |
Site Public Contact 913-945-7552 ctnursenav@kumc.edu |
University of Kansas Hospital-Westwood Cancer Center Westwood, Kansas 66205 United States |
Recruiting |
Site Public Contact 913-945-7552 ctnursenav@kumc.edu |
University of Kentucky/Markey Cancer Center Lexington, Kentucky 40536 United States |
Recruiting |
Site Public Contact 859-257-3379 |
Johns Hopkins University/Sidney Kimmel Cancer Center Baltimore, Maryland 21287 United States |
Recruiting |
Site Public Contact 410-955-8804 jhcccro@jhmi.edu |
Massachusetts General Hospital Cancer Center Boston, Massachusetts 02114 United States |
Recruiting |
Site Public Contact 877-726-5130 |
Brigham and Women's Hospital Boston, Massachusetts 02115 United States |
Recruiting |
Site Public Contact 617-724-5200 |
Beth Israel Deaconess Medical Center Boston, Massachusetts 02215 United States |
Recruiting |
Site Public Contact 617-667-9925 |
Dana-Farber Cancer Institute Boston, Massachusetts 02215 United States |
Recruiting |
Site Public Contact 877-442-3324 |
Wayne State University/Karmanos Cancer Institute Detroit, Michigan 48201 United States |
Recruiting |
Site Public Contact 313-576-9790 ctoadmin@karmanos.org |
Weisberg Cancer Treatment Center Farmington Hills, Michigan 48334 United States |
Recruiting |
Site Public Contact 313-576-9790 ctoadmin@karmanos.org |
Mayo Clinic Rochester, Minnesota 55905 United States |
Recruiting |
Site Public Contact 855-776-0015 |
Siteman Cancer Center at West County Hospital Creve Coeur, Missouri 63141 United States |
Active, not recruiting | |
Washington University School of Medicine Saint Louis, Missouri 63110 United States |
Active, not recruiting | |
Siteman Cancer Center-South County Saint Louis, Missouri 63129 United States |
Active, not recruiting | |
Siteman Cancer Center at Christian Hospital Saint Louis, Missouri 63136 United States |
Active, not recruiting | |
Nebraska Medicine-Bellevue Bellevue, Nebraska 68123 United States |
Recruiting |
Site Public Contact 402-559-6941 unmcrsa@unmc.edu |
Nebraska Medicine-Village Pointe Omaha, Nebraska 68118 United States |
Recruiting |
Site Public Contact 402-559-5600 |
University of Nebraska Medical Center Omaha, Nebraska 68198 United States |
Recruiting |
Site Public Contact 402-559-6941 unmcrsa@unmc.edu |
UNC Lineberger Comprehensive Cancer Center Chapel Hill, North Carolina 27599 United States |
Recruiting |
Site Public Contact 877-668-0683 cancerclinicaltrials@med.unc.edu |
Duke University Medical Center Durham, North Carolina 27710 United States |
Recruiting |
Site Public Contact 888-275-3853 |
Case Western Reserve University Cleveland, Ohio 44106 United States |
Recruiting |
Site Public Contact 800-641-2422 CTUReferral@UHhospitals.org |
Ohio State University Comprehensive Cancer Center Columbus, Ohio 43210 United States |
Recruiting |
Site Public Contact 800-293-5066 Jamesline@osumc.edu |
University of Pittsburgh Cancer Institute (UPCI) Pittsburgh, Pennsylvania 15232 United States |
Recruiting |
Site Public Contact 412-647-8073 |
Vanderbilt Breast Center at One Hundred Oaks Nashville, Tennessee 37204 United States |
Recruiting |
Site Public Contact 800-811-8480 |
Vanderbilt University/Ingram Cancer Center Nashville, Tennessee 37232 United States |
Recruiting |
Site Public Contact 800-811-8480 |
University of Virginia Cancer Center Charlottesville, Virginia 22908 United States |
Recruiting |
Site Public Contact 434-243-6303 PAS9E@virginia.edu |
University of Wisconsin Hospital and Clinics Madison, Wisconsin 53792 United States |
Recruiting |
Site Public Contact 800-622-8922 |