Combination Chemotherapy With or Without Vismodegib in Treating Patients With Advanced Stomach Cancer or Gastroesophageal Junction Cancer
A Randomized, Double Blind Placebo Controlled Phase 2 Study of FOLFOX Plus or Minus GDC-0449 in Patients With Advanced Gastric and Gastroesophageal Junction (GEJ) Carcinoma
9 other identifiers
interventional
124
1 country
30
Brief Summary
This randomized phase II trial studies combination chemotherapy when given together with vismodegib to see how well it works compared with combination chemotherapy without vismodegib in treating patients with advanced stomach cancer or gastroesophageal junction cancer. Drugs used in chemotherapy, such as oxaliplatin, leucovorin calcium, and fluorouracil, 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. Giving more than one drug (combination chemotherapy) may kill more tumor cells. Vismodegib may stop the growth of stomach or gastroesophageal junction cancer by blocking the growth of new blood vessels necessary for tumor growth. It is not yet known whether combination chemotherapy is more effective when given with or without vismodegib in treating stomach cancer and gastroesophageal junction cancer.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started Sep 2009
Longer than P75 for phase_2
30 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
September 1, 2009
CompletedFirst Submitted
Initial submission to the registry
September 22, 2009
CompletedFirst Posted
Study publicly available on registry
September 23, 2009
CompletedPrimary Completion
Last participant's last visit for primary outcome
April 1, 2012
CompletedStudy Completion
Last participant's last visit for all outcomes
October 1, 2014
CompletedResults Posted
Study results publicly available
January 25, 2016
CompletedJanuary 25, 2016
August 1, 2015
2.6 years
September 22, 2009
December 16, 2015
December 16, 2015
Conditions
Outcome Measures
Primary Outcomes (1)
Median Progression-free Survival (PFS)
PFS is defined as the time from randomization until objective tumor progression or death from any cause and is evaluated per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
up to 4 years
Secondary Outcomes (4)
Objective Response Rate
Up to 4 years
Overall Survival
up to 4 years
Incidence of Toxicities (Grade 3 and Higher)
Up to 4 years
Incidence of Toxicities (grades1 and 2)
Up to 4 years
Study Arms (2)
Arm I (FOLFOX regimen and placebo)
EXPERIMENTALPatients receive FOLFOX chemotherapy comprising oxaliplatin IV over 2 hours, leucovorin calcium IV over 2 hours, and fluorouracil bolus and then IV over 46-48 hours on day 1. Patients also receive placebo PO QD on days 1-14. Courses repeat every 2 weeks in the absence of unacceptable toxicity or disease progression.
Arm II (FOLFOX regimen and vismodegib)
EXPERIMENTALPatients receive FOLFOX chemotherapy as in arm I. Patients also receive vismodegib PO on days 1-14. Courses repeat every 2 weeks in the absence of unacceptable toxicity or disease progression.
Interventions
Given IV
Given IV
Given IV
Given PO
Correlative studies
Eligibility Criteria
You may qualify if:
- Patients must have histologically or cytologically confirmed gastric or gastroesophageal junction (GEJ) adenocarcinoma not amenable to surgical resection
- 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) as \>= 20 mm with conventional techniques or as \>= 10 mm with spiral computed tomography (CT) scan
- No prior chemotherapy for advanced disease; patients may have receive adjuvant chemotherapy or chemoradiation if \> 6 months has elapsed since completion of treatment
- Life expectancy of greater than 3 months
- Eastern Cooperative Oncology Group (ECOG) performance status \< 2 (Karnofsky \> 70%)
- Absolute neutrophil count \>= 1,500/mcL
- Platelets \>= 100,000/mcL
- Total bilirubin =\< 1.5 times upper limit of normal (ULN)
- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 X institutional upper limit of normal (=\< 5.0 X institutional upper limit of normal with presence of liver metastases)
- Creatinine =\< 1.5 X institutional upper limit of normal OR creatinine clearance \>= 60 mL/min/1.73 m\^2 for patients with creatinine levels above institutional normal
- Baseline imaging studies performed =\< 28 days of study registration; the treating investigator will determine the appropriate imaging studies, which may include CT scan, magnetic resonance imaging (MRI), and/or fludeoxyglucose F 18 (FDG)-positron emission tomography (PET)/CT
- Must be willing to provide blood and tissue samples for research purposes; patient has the right to later withdraw consent for research studies and/or tissue specimens
- Patients must agree to placement of a central venous catheter for chemotherapy administration
- Patients must be able to swallow whole capsules
- Patients taking medications with narrow therapeutic indices that are metabolized by cytochrome P450 (CYP450), including warfarin sodium (Coumadin), must be on a stable, therapeutic dose and have close monitoring of their levels
- +10 more criteria
You may not qualify if:
- Patients who have had chemotherapy or radiotherapy within 6 months prior to entering the study
- Patients may not be receiving any other investigational agents
- Patients with known brain metastases should be excluded from this clinical trial
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to GDC-0449, 5-fluorouracil or oxaliplatin
- GDC-0449 inhibits cytochrome P450, family 2, subfamily C, polypeptide 8 (CYP2C8), cytochrome P450, family 2, subfamily C, polypeptide 9 (CYP2C9), and cytochrome P450, family 2, subfamily C, polypeptide 19 (CYP2C19) drug metabolism enzymes in vitro at concentrations that may be clinically relevant; therefore, caution should be exercised when dosing GDC-0449 concurrently with medications that are substrates of CYP2C8, CYP2C9, and CYP2C19 and have narrow therapeutic windows
- Patients with malabsorption syndrome or other condition that would interfere with intestinal absorption
- Patients unable to swallow whole capsules
- Patients with clinically active liver disease, including viral or other hepatitis or cirrhosis are ineligible
- Patients with uncontrolled hypocalcemia, hypomagnesemia, hyponatremia or hypokalemia defined as less than the lower limit of normal for the institution, despite adequate electrolyte supplementation are excluded from this study
- Pre-existing \> grade 1 peripheral sensory neuropathy
- Previous or concurrent malignancy; exceptions: treated basal cell or squamous cell skin cancer, in situ cervical cancer, or lobular carcinoma in situ in one breast; or other cancer which the patient has been disease-free ≥5 years
- 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 GDC-0449
- Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (30)
University of California at Davis Cancer Center
Sacramento, California, 95817, United States
University of Chicago
Chicago, Illinois, 60637, United States
Cancer Care Center of Decatur
Decatur, Illinois, 62526, United States
Decatur Memorial Hospital
Decatur, Illinois, 62526, United States
Crossroads Cancer Center
Effingham, Illinois, 62401, United States
NorthShore University HealthSystem-Evanston Hospital
Evanston, Illinois, 60201, United States
Ingalls Memorial Hospital
Harvey, Illinois, 60426, United States
Loyola University Medical Center
Maywood, Illinois, 60153, United States
Illinois CancerCare-Peoria
Peoria, Illinois, 61615, United States
Illinois Oncology Research Association CCOP
Peoria, Illinois, 61615, United States
Memorial Medical Center
Springfield, Illinois, 62781-0001, United States
Fort Wayne Medical Oncology and Hematology Inc-Parkview
Fort Wayne, Indiana, 46845, United States
Indiana University Medical Center
Indianapolis, Indiana, 46202, United States
University of Michigan University Hospital
Ann Arbor, Michigan, 48109, United States
University of Michigan
Ann Arbor, Michigan, 48109, United States
Saint John's Mercy Medical Center
St Louis, Missouri, 63141, United States
Beth Israel Medical Center
New York, New York, 10003, United States
New York University Langone Medical Center
New York, New York, 10016, United States
Saint Luke's Roosevelt Hospital Center - Saint Luke's Division
New York, New York, 10025, United States
Columbia University Medical Center
New York, New York, 10032, United States
Memorial Sloan-Kettering Cancer Center
New York, New York, 10065, United States
Weill Medical College of Cornell University
New York, New York, 10065, United States
Albert Einstein College of Medicine
The Bronx, New York, 10461, United States
New York Cancer Consortium
The Bronx, New York, 10461, United States
Montefiore Medical Center - Moses Campus
The Bronx, New York, 10467-2490, United States
Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center
Columbus, Ohio, 43210, United States
Ohio State University Medical Center
Columbus, Ohio, 43210, United States
University of Pittsburgh
Pittsburgh, Pennsylvania, 15232, United States
Vanderbilt-Ingram Cancer Center
Nashville, Tennessee, 37232, United States
Virginia Commonwealth University
Richmond, Virginia, 23298, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Deirdre Cohen, MD
- Organization
- Perlmutter Cancer Center at NYU Langone
Study Officials
- PRINCIPAL INVESTIGATOR
Deirdre Cohen
NYU Langone Health
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- LTE60
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- DOUBLE
- Who Masked
- PARTICIPANT, INVESTIGATOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
September 22, 2009
First Posted
September 23, 2009
Study Start
September 1, 2009
Primary Completion
April 1, 2012
Study Completion
October 1, 2014
Last Updated
January 25, 2016
Results First Posted
January 25, 2016
Record last verified: 2015-08