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BRIEF TITLE: Cisplatin/Gemcitabine With or Without M6620 (VX-970) in Metastatic Urothelial Carcinoma

A Randomized Phase 2 Trial of Cisplatin/Gemcitabine With or Without M6620 (VX-970) in Metastatic Urothelial Carcinoma


  • Org Study ID: NCI-2015-01642
  • Secondary ID: NCI-2015-01642,PHII-135,9947,9947,N01CM00038,UM1CA186690,UM1CA186717
  • NCT ID: NCT02567409
  • NCT Alias:
  • Sponsor: National Cancer Institute (NCI) - NIH
  • Source: 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 (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.

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
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 Outcomes:

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

Condition:

  • Metastatic Bladder Urothelial Carcinoma
  • Metastatic Renal Pelvis and Ureter Urothelial Carcinoma
  • Metastatic Ureter Urothelial Carcinoma
  • Stage IV Bladder Urothelial Carcinoma AJCC v7

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
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Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

Official Information

Name: Sumanta K Pal

Role: Principal Investigator

Affiliation: City of Hope Comprehensive Cancer Center LAO

Locations

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