Combination Chemotherapy With or Without GDC-0449 in Treating Patients With Advanced Stomach Cancer or Gastroesophageal Junction Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00982592
First received: September 22, 2009
Last updated: August 26, 2013
Last verified: August 2013
  Purpose

This randomized phase II trial is studying giving combination chemotherapy together with GDC-0449 to see how well it works compared with giving combination chemotherapy without GDC-0449 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 or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells. GDC-0449 may block the growth of tumor cells. It is not yet known whether combination chemotherapy is more effective when given with or without GDC-0449 in treating stomach cancer and gastroesophageal junction cancer.


Condition Intervention Phase
Adenocarcinoma of the Gastroesophageal Junction
Adenocarcinoma of the Stomach
Recurrent Gastric Cancer
Stage III Gastric Cancer
Stage IV Gastric Cancer
Drug: FOLFOX regimen
Drug: vismodegib
Other: hydrocortisone/placebo
Drug: oxaliplatin
Drug: leucovorin calcium
Drug: fluorouracil
Other: flow cytometry
Other: enzyme-linked immunosorbent assay
Genetic: reverse transcriptase-polymerase chain reaction
Other: laboratory biomarker analysis
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Median progression-free survival [ Time Frame: Time from randomization day until objective or symptomatic progression or death from any cause, assessed up to 2 years ] [ Designated as safety issue: No ]
    The PFS distributions of the two treatment arms will be estimated by Kaplan-Meier survival analysis and the PFS distributions will be compared by an unstratified log-rank test. Ninety-five percent confidence intervals for the Kaplan-Meier PFS estimates will be calculated using Greenwood's formulae.


Secondary Outcome Measures:
  • Objective response rate (CR+PR) [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
    Estimated via binomial proportions. Ninety-five percent confidence intervals will be calculated for the objective response proportion in each group via binomial proportions. Comparison of the objective response rate between the treatment groups will be performed by the chi-square test or Fisher's exact test, as appropriate. Response will be evaluated in this study using the new international criteria proposed by the revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1).

  • Overall survival [ Time Frame: Time from randomization day until death from any cause, assessed up to 2 years ] [ Designated as safety issue: No ]
    Estimated by Kaplan-Meier. The comparison of the overall survival distributions between the treatment groups will be performed by the log-rank test.

  • Toxicity as assessed by NCI CTCAE v4.0 [ Time Frame: Up to 2 years ] [ Designated as safety issue: Yes ]
    The frequency of subjects experiencing toxicities will be tabulated. Exact 95% confidence intervals around the toxicity proportions will be calculated to assess the precision of the obtained estimates.


Estimated Enrollment: 116
Study Start Date: September 2009
Primary Completion Date: April 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I (FOLFOX regimen and placebo)
Patients receive FOLFOX chemotherapy comprising oxaliplatin IV over 2 hours, leucovorin calcium IV over 2 hours, and fluorouracil IV over 46-48 hours on day 1. Patients also receive placebo PO QD on days 1-14. Treatment repeats every 2 weeks in the absence of unacceptable toxicity or disease progression.
Drug: FOLFOX regimen
Given IV
Other Name: FOLinic acid-Fluororuracil-OXaliplatin regimen
Other: hydrocortisone/placebo
Given PO
Drug: oxaliplatin
Given IV
Other Names:
  • 1-OHP
  • Dacotin
  • Dacplat
  • Eloxatin
  • L-OHP
Drug: leucovorin calcium
Given IV
Other Names:
  • CF
  • CFR
  • LV
Drug: fluorouracil
Given IV
Other Names:
  • 5-fluorouracil
  • 5-Fluracil
  • 5-FU
Other: flow cytometry
Correlative studies
Other: enzyme-linked immunosorbent assay
Correlative studies
Other Name: ELISA
Genetic: reverse transcriptase-polymerase chain reaction
Correlative studies
Other Name: RT-PCR
Experimental: Arm II (FOLFOX regimen and vismodegib)
Patients receive FOLFOX chemotherapy as in arm I. Patients also receive hedgehog antagonist GDC-0449 PO on days 1-14. Treatment repeats every 2 weeks in the absence of unacceptable toxicity or disease progression.
Drug: FOLFOX regimen
Given IV
Other Name: FOLinic acid-Fluororuracil-OXaliplatin regimen
Drug: vismodegib
Given PO
Other Names:
  • Erivedge
  • GDC-0449
  • Hedgehog antagonist GDC-0449
Drug: oxaliplatin
Given IV
Other Names:
  • 1-OHP
  • Dacotin
  • Dacplat
  • Eloxatin
  • L-OHP
Drug: leucovorin calcium
Given IV
Other Names:
  • CF
  • CFR
  • LV
Drug: fluorouracil
Given IV
Other Names:
  • 5-fluorouracil
  • 5-Fluracil
  • 5-FU
Other: flow cytometry
Correlative studies
Other: enzyme-linked immunosorbent assay
Correlative studies
Other Name: ELISA
Genetic: reverse transcriptase-polymerase chain reaction
Correlative studies
Other Name: RT-PCR
Other: laboratory biomarker analysis
Correlative studies

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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
  • Must be willing to provide blood and tissue samples for research purposes
  • No known brain metastases
  • Eastern Cooperative Oncology Group (ECOG) performance status < 2 (Karnofsky > 70%)
  • Life expectancy > 3 months
  • Absolute neutrophil count >= 1,500/mcL
  • Platelets >= 100,000/mcL
  • Total bilirubin =< 1.5 times upper limit of normal (ULN)
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 times ULN (=< 5.0 times ULN in the presence of liver metastases)
  • Creatinine =< 1.5X institutional upper limit of normal OR creatinine clearance >= 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use 2 forms of effective contraception (i.e., barrier contraception and one other method of contraception) for >= 4 weeks before, during, and >= 12 months after completion of study treatment
  • Must agree to placement of a central venous catheter for chemotherapy administration
  • No history of allergic reactions attributed to compounds of similar chemical or biologic composition to hedgehog antagonist GDC-0449, fluorouracil, or oxaliplatin
  • No malabsorption syndrome or other condition that would interfere with intestinal absorption
  • Able to swallow whole capsules
  • No clinically active liver disease, including viral or other hepatitis or cirrhosis
  • No uncontrolled hypocalcemia, hypomagnesemia, hyponatremia, or hypokalemia defined as less than the lower limit of normal for the institution, despite adequate electrolyte supplementation
  • No pre-existing peripheral sensory neuropathy > grade 1
  • No previous or other concurrent malignancy, except treated basal cell or squamous cell skin cancer, in situ cervical cancer, lobular carcinoma in situ in one breast, or other cancer from which the patient has been disease-free >= 5 years
  • No 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
  • Medications with narrow therapeutic indices that are metabolized by cytochrome P450 (CYP450), including warfarin sodium (coumadin) are allowed as long as on a stable therapeutic dose
  • More than 6 months since prior adjuvant chemotherapy or chemoradiation
  • No prior chemotherapy for advanced disease
  • No concurrent combination antiretroviral therapy for human immunodeficiency virus (HIV)-positive patients
  • No other concurrent investigational agents
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00982592

Locations
United States, California
UC Davis Comprehensive Cancer Center
Sacramento, California, United States, 95817
United States, Illinois
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, United States, 60637-1470
Cancer Care Center of Decatur
Decatur, Illinois, United States, 62526
Decatur Memorial Hospital
Decatur, Illinois, United States, 62526
Crossroads Cancer Center
Effingham, Illinois, United States, 62401
Evanston CCOP-NorthShore University HealthSystem
Evanston, Illinois, United States, 60201
Ingalls Memorial Hospital
Harvey, Illinois, United States, 60426
Loyola University Medical Center
Maywood, Illinois, United States, 60153
Illinois CancerCare-Peoria
Peoria, Illinois, United States, 61615
Illinois Oncology Research Association CCOP
Peoria, Illinois, United States, 61615
Memorial Medical Center
Springfield, Illinois, United States, 62781-0001
United States, Indiana
Fort Wayne Medical Oncology and Hematology Inc - State Boulevard
Fort Wayne, Indiana, United States, 46845
Indiana University Medical Center
Indianapolis, Indiana, United States, 46202
United States, Michigan
University of Michigan
Ann Arbor, Michigan, United States, 48109
United States, Missouri
Saint John's Mercy Medical Center
Saint Louis, Missouri, United States, 63141
United States, New York
Albert Einstein College of Medicine
Bronx, New York, United States, 10461
Montefiore Medical Center
Bronx, New York, United States, 10467-2490
New York Cancer Consortium
Bronx;, New York, United States, 10461
Memorial Sloan Kettering Cancer Center
New York, New York, United States, 10065
Beth Israel Medical Center
New York, New York, United States, 10003
Columbia University Medical Center
New York, New York, United States, 10032
New York University Langone Medical Center
New York, New York, United States, 10016
Saint Luke's Roosevelt Hospital Center - Saint Luke's Division
New York, New York, United States, 10025
Weill Medical College of Cornell University
New York, New York, United States, 10065
United States, Ohio
Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center
Columbus, Ohio, United States, 43210
Ohio State University Medical Center
Columbus, Ohio, United States, 43210
United States, Pennsylvania
University of Pittsburgh
Pittsburgh, Pennsylvania, United States, 15232
United States, Tennessee
Vanderbilt-Ingram Cancer Center
Nashville, Tennessee, United States, 37232
United States, Virginia
Virginia Commonwealth University
Richmond, Virginia, United States, 23298
Sponsors and Collaborators
Investigators
Principal Investigator: Deirdre Cohen New York University Langone Medical Center
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00982592     History of Changes
Other Study ID Numbers: NCI-2011-01425, NCI-2011-01425, 09-0356, CDR0000655339, NYU 09-0356, 8376, N01CM00070, N01CM00071, N01CM00038, P30CA016087
Study First Received: September 22, 2009
Last Updated: August 26, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Adenocarcinoma
Stomach Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Stomach Diseases
Fluorouracil
Oxaliplatin
Cortisol succinate
Hydrocortisone acetate
Hydrocortisone 17-butyrate 21-propionate
Hydrocortisone
Hydrocortisone-17-butyrate
Leucovorin
Levoleucovorin
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antimetabolites, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on July 22, 2014