Cisplatin and Gemcitabine Hydrochloride With or Without ATR Kinase Inhibitor M6620 in Treating Patients With Metastatic Urothelial Cancer
Status: | Recruiting |
---|---|
Healthy: | No |
Age Range: | 18 - Any |
Updated: | 3/23/2019 |
Start Date: | August 19, 2016 |
A Randomized Phase 2 Trial of Cisplatin/Gemcitabine With or Without M6620 (VX-970) in Metastatic Urothelial Carcinoma
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.
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.
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
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.
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
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.
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
We found this trial at
35
sites
Newport Beach, California 92663
Principal Investigator: Sarmad Sadeghi
Phone: 323-865-0451
Click here to add this to my saved trials
75 Francis street
Boston, Massachusetts 02115
Boston, Massachusetts 02115
(617) 732-5500
Principal Investigator: Philip J. Saylor
Phone: 888-823-5923
Brigham and Women's Hosp Boston’s Brigham and Women’s Hospital (BWH) is an international leader in...
Click here to add this to my saved trials
330 Brookline Ave
Boston, Massachusetts 02215
Boston, Massachusetts 02215
617-667-7000
Principal Investigator: Philip J. Saylor
Phone: 617-667-9925
Beth Israel Deaconess Medical Center Beth Israel Deaconess Medical Center (BIDMC) is one of the...
Click here to add this to my saved trials
1300 Jefferson Park Avenue
Charlottesville, Virginia 22908
Charlottesville, Virginia 22908
434-243-6784
Principal Investigator: Robert Dreicer
Phone: 434-243-6303
University of Virginia Cancer Center We are fortunate in having state of the art clinical...
Click here to add this to my saved trials
1500 E Duarte Rd
Duarte, California 91010
Duarte, California 91010
(626) 256-4673
Principal Investigator: Sumanta K. Pal
Phone: 800-826-4673
City of Hope Comprehensive Cancer Center City of Hope is a leading research and treatment...
Click here to add this to my saved trials
Atlanta, Georgia 30322
Principal Investigator: Bradley C. Carthon
Phone: 404-778-1868
Click here to add this to my saved trials
12605 East 16th Avenue
Aurora, Colorado 80045
Aurora, Colorado 80045
720-848-0000
Principal Investigator: Thomas W. Flaig
Phone: 720-848-0650
University of Colorado Hospital, Site Top medical professionals, superior medicine and progressive change make University...
Click here to add this to my saved trials
401 North Broadway
Baltimore, Maryland 21287
Baltimore, Maryland 21287
410-955-5000
Principal Investigator: Noah M. Hahn
Phone: 410-955-8804
Johns Hopkins University-Sidney Kimmel Cancer Center The name Johns Hopkins has become synonymous with excellence...
Click here to add this to my saved trials
55 Fruit St
Boston, Massachusetts 02114
Boston, Massachusetts 02114
(617) 724-4000
Principal Investigator: Philip J. Saylor
Phone: 877-726-5130
Massachusetts General Hospital Cancer Center An integral part of one of the world
Click here to add this to my saved trials
450 Brookline Ave
Boston, Massachusetts 2215
Boston, Massachusetts 2215
617-632-3000
Principal Investigator: Philip J. Saylor
Phone: 877-442-3324
Dana-Farber Cancer Institute Since it’s founding in 1947, Dana-Farber has been committed to providing adults...
Click here to add this to my saved trials
Chapel Hill, North Carolina 27599
Principal Investigator: Matthew I. Milowsky
Phone: 877-668-0683
Click here to add this to my saved trials
10900 Euclid Ave
Cleveland, Ohio 44106
Cleveland, Ohio 44106
216-368-2000
Principal Investigator: Christopher J. Hoimes
Phone: 800-641-2422
Case Western Reserve Univ Continually ranked among America's best colleges, Case Western Reserve University has...
Click here to add this to my saved trials
Columbus, Ohio 43210
Principal Investigator: Amir Mortazavi
Phone: 800-293-5066
Click here to add this to my saved trials
10 Barnes West Drive
Creve Coeur, Missouri 63141
Creve Coeur, Missouri 63141
Principal Investigator: Joel Picus
Phone: 800-600-3606
Click here to add this to my saved trials
4160 John R St #2122
Detroit, Michigan 48201
Detroit, Michigan 48201
(313) 833-1785
Principal Investigator: Ulka N. Vaishampayan
Phone: 313-576-9790
Wayne State University/Karmanos Cancer Institute Karmanos is based in southeast Michigan, in midtown Detroit, and...
Click here to add this to my saved trials
2301 Erwin Rd
Durham, North Carolina 27710
Durham, North Carolina 27710
919-684-8111
Principal Investigator: James L. Abbruzzese
Phone: 888-275-3853
Duke Univ Med Ctr As a world-class academic and health care system, Duke Medicine strives...
Click here to add this to my saved trials
Fairway, Kansas 66205
Principal Investigator: Rahul A. Parikh
Phone: 913-945-7552
Click here to add this to my saved trials
Farmington Hills, Michigan 48334
Principal Investigator: Ulka N. Vaishampayan
Phone: 313-576-9790
Click here to add this to my saved trials
4500 San Pablo Rd S
Jacksonville, Florida 32224
Jacksonville, Florida 32224
(904) 953-2000
Principal Investigator: Parminder Singh
Phone: 855-776-0015
Mayo Clinic Florida Thousands of people come to Mayo Clinic in Jacksonville, Fla., annually for...
Click here to add this to my saved trials
Lexington, Kentucky
Principal Investigator: Peng Wang
Phone: 859-257-3379
Click here to add this to my saved trials
1983 Marengo St
Los Angeles, California 90033
Los Angeles, California 90033
(323) 226-2622
Principal Investigator: Sarmad Sadeghi
Phone: 323-865-0451
Los Angeles County-USC Medical Center The origins of LAC+USC Medical Center date back to 1878,...
Click here to add this to my saved trials
1441 Eastlake Ave
Los Angeles, California 90033
Los Angeles, California 90033
(323) 865-3000
Principal Investigator: Sarmad Sadeghi
Phone: 323-865-0451
U.S.C./Norris Comprehensive Cancer Center The USC Norris Comprehensive Cancer Center, located in Los Angeles, is...
Click here to add this to my saved trials
600 Highland Ave
Madison, Wisconsin 53792
Madison, Wisconsin 53792
(608) 263-6400
Principal Investigator: Hamid Emamekhoo
Phone: 800-622-8922
University of Wisconsin Hospital and Clinics UW Health strives to meet the health needs of...
Click here to add this to my saved trials
Nashville, Tennessee 37232
Principal Investigator: Nancy B. Davis
Phone: 800-811-8480
Click here to add this to my saved trials
875 Blake Wilbur Drive
Palo Alto, California 94304
Palo Alto, California 94304
Principal Investigator: Sandy Srinivas
Phone: 650-498-7061
Click here to add this to my saved trials
Pasadena, California 91105
Principal Investigator: Sarmad Sadeghi
Phone: 323-865-0451
Click here to add this to my saved trials
Click here to add this to my saved trials
Pittsburgh, Pennsylvania 15232
Principal Investigator: Leonard J. Appleman
Phone: 412-647-8073
Click here to add this to my saved trials
Rochester, Minnesota 55905
Principal Investigator: Parminder Singh
Phone: 855-776-0015
Click here to add this to my saved trials
Sacramento, California 95817
Principal Investigator: Primo N. Lara
Phone: 916-734-3089
Click here to add this to my saved trials
660 S Euclid Ave
Saint Louis, Missouri 63110
Saint Louis, Missouri 63110
(314) 362-5000
Principal Investigator: Joel Picus
Phone: 800-600-3606
Washington University School of Medicine Washington University Physicians is the clinical practice of the School...
Click here to add this to my saved trials
Saint Louis, Missouri 63129
Principal Investigator: Joel Picus
Phone: 800-600-3606
Click here to add this to my saved trials
11155 Dunn Road
Saint Louis, Missouri 63136
Saint Louis, Missouri 63136
Principal Investigator: Joel Picus
Phone: 800-600-3606
Click here to add this to my saved trials
13400 E. Shea Blvd.
Scottsdale, Arizona 85259
Scottsdale, Arizona 85259
480-301-8000
Principal Investigator: Parminder Singh
Phone: 855-776-0015
Mayo Clinic Arizona Mayo Clinic in Arizona provides medical care for thousands of people from...
Click here to add this to my saved trials
Westwood, Kansas 66205
Principal Investigator: Rahul A. Parikh
Phone: 913-945-7552
Click here to add this to my saved trials