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BRIEF TITLE: A Randomized Phase 2 Trial of Cisplatin/Gemcitabine With or Without VX-970 in Metastatic Urothelial Carcinoma

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


  • Org Study ID: NCI-2015-01642
  • Secondary ID: NCI-2015-01642,PHII-135,9947,9947,N01CM00038,P30CA033572,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 VX-970 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 VX-970 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 VX-970 in treating patients with urothelial cancer.

Detailed Description


PRIMARY OBJECTIVES:

I. To determine if the addition of ATR kinase inhibitor VX-970 (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 VX-970 to cisplatin/gemcitabine
relative to cisplatin/gemcitabine alone.

II. To compare tumor response rate with the addition of VX-970 to cisplatin/gemcitabine
relative to cisplatin/gemcitabine alone.

III. To compare safety with the addition of VX-970 to cisplatin/gemcitabine relative to
cisplatin/gemcitabine alone.

IV. To assess the role of p53 status in predicting response to 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 VX-970 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.

Overal Status Start Date Phase Study Type
Recruiting August 19, 2016 Phase 2 Interventional

Primary Outcomes:

Primary Outcome 1 - Measure: Progression-free survival

Primary Outcome 1 - Time Frame: Day of randomization, until progression, death, or the start of another treatment, assessed up to 12 months

Condition:

  • Metastatic Urothelial Carcinoma of the Renal Pelvis and Ureter
  • Stage IV Bladder Urothelial Carcinoma

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

- 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 normal institutional limits

- 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 or calculated clearance

- 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 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 VX-970, 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 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 Pal

Role: Principal Investigator

Affiliation: City of Hope Comprehensive Cancer Center LAO

Locations

Facility Status Contact
City of Hope Comprehensive Cancer Center LAO
Duarte, California 91010
United States
Recruiting Sumanta K. Pal
800-826-4673
becomingapatient@coh.org
City of Hope Comprehensive Cancer Center
Duarte, California 91010
United States
Recruiting Sumanta K. Pal
800-826-4673
becomingapatient@coh.org
Los Angeles County-USC Medical Center
Los Angeles, California 90033
United States
Recruiting Tanya B. Dorff
323-865-0451
USC / Norris Comprehensive Cancer Center
Los Angeles, California 90033
United States
Recruiting Tanya B. Dorff
323-865-0451
Stanford Cancer Institute
Palo Alto, California 94304
United States
Recruiting Sandy Srinivas
650-498-7061
clinicaltrials@med.stanford.edu
Keck Medical Center of USC Pasadena
Pasadena, California 91105
United States
Recruiting Tanya B. Dorff
323-865-0451
University of California Davis Comprehensive Cancer Center
Sacramento, California 95817
United States
Recruiting Primo N. Lara
916-734-3089
University of Colorado Cancer Center - Anschutz Cancer Pavilion
Aurora, Colorado 80045
United States
Recruiting Thomas W. Flaig
720-848-0650
Emory University/Winship Cancer Institute
Atlanta, Georgia 30322
United States
Recruiting Bradley C. Carthon
404-778-1868
University of Kentucky/Markey Cancer Center
Lexington, Kentucky 40536
United States
Recruiting Peng Wang
859-257-3379
Johns Hopkins University/Sidney Kimmel Cancer Center
Baltimore, Maryland 21287
United States
Recruiting Noah M. Hahn
410-955-8804
jhcccro@jhmi.edu
Massachusetts General Hospital Cancer Center
Boston, Massachusetts 02114
United States
Recruiting Philip J. Saylor
877-726-5130
psaylor@mgh.harvard.edu
Brigham and Women's Hospital
Boston, Massachusetts 02115
United States
Recruiting Philip J. Saylor
877-726-5130
psaylor@mgh.harvard.edu
Beth Israel Deaconess Medical Center
Boston, Massachusetts 02215
United States
Recruiting Philip J. Saylor
877-726-5130
psaylor@mgh.harvard.edu
Dana-Farber Cancer Institute
Boston, Massachusetts 02215
United States
Recruiting Philip J. Saylor
877-726-5130
psaylor@mgh.harvard.edu
Wayne State University/Karmanos Cancer Institute
Detroit, Michigan 48201
United States
Recruiting Ulka N. Vaishampayan
313-576-9363
Barnes-Jewish West County Hospital
Creve Coeur, Missouri 63141
United States
Recruiting Joel Picus
800-600-3606
info@siteman.wustl.edu
Washington University School of Medicine
Saint Louis, Missouri 63110
United States
Recruiting Joel Picus
800-600-3606
info@siteman.wustl.edu
Siteman Cancer Center-South County
Saint Louis, Missouri 63129
United States
Recruiting Joel Picus
800-600-3606
info@siteman.wustl.edu
UNC Lineberger Comprehensive Cancer Center
Chapel Hill, North Carolina 27599
United States
Recruiting Matthew I. Milowsky
877-668-0683
cancerclinicaltrials@med.unc.edu
Duke University Medical Center
Durham, North Carolina 27710
United States
Recruiting Herbert I. Hurwitz
888-275-3853
Case Western Reserve University
Cleveland, Ohio 44106
United States
Recruiting Christopher J. Hoimes
800-641-2422
christopher.hoimes@case.edu
Ohio State University Comprehensive Cancer Center
Columbus, Ohio 43210
United States
Recruiting Amir Mortazavi
800-293-5066
Jamesline@osumc.edu
University of Pittsburgh Cancer Institute (UPCI)
Pittsburgh, Pennsylvania 15232
United States
Recruiting Rahul A. Parikh
412-647-8073
Vanderbilt University/Ingram Cancer Center
Nashville, Tennessee 37232
United States
Recruiting David D. Chism
800-811-8480
University of Virginia Cancer Center
Charlottesville, Virginia 22908
United States
Recruiting Robert Dreicer
434-243-6322
JME3D@hscmail.mcc.virginia.edu
University of Wisconsin Hospital and Clinics
Madison, Wisconsin 53792
United States
Recruiting Hamid Emamekhoo
800-622-8922