Combination Chemotherapy With or Without GDC-0449 in Treating Patients With Advanced Stomach Cancer or Gastroesophageal Junction Cancer
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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 |
Phase 2 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized 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 |
- Median progression-free survival [ Time Frame: Not Provided ] [ Designated as safety issue: No ]
- Objective response rate [ Time Frame: Not Provided ] [ Designated as safety issue: No ]
- Overall survival [ Time Frame: Not Provided ] [ Designated as safety issue: No ]
- Toxicity as assessed by NCI CTCAE v3.0 [ Time Frame: Not Provided ] [ Designated as safety issue: Yes ]
- Hedgehog-signaling pathway expression [ Time Frame: Not Provided ] [ Designated as safety issue: No ]
- Gene-expression profile and clinical outcome [ Time Frame: Not Provided ] [ Designated as safety issue: No ]
- Shed epitopes as a measure of response in the microenvironment [ Time Frame: Not Provided ] [ Designated as safety issue: No ]
- Circulating endothelial progenitor cells as a marker of response to hedgehog antagonist GDC-0449/placebo treatment [ Time Frame: Not Provided ] [ Designated as safety issue: No ]
- Serum growth-factor levels as a measure of response in the microenvironment [ Time Frame: Not Provided ] [ Designated as safety issue: No ]
| 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
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 oral placebo once daily 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 orally
Drug: oxaliplatin
Given IV
Other Names:
Drug: leucovorin calcium
Given IV
Other Names:
Drug: fluorouracil
Given IV
Other Names:
|
|
Experimental: Arm II
Patients receive FOLFOX chemotherapy as in arm I. Patients also receive oral hedgehog antagonist GDC-0449 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 orally
Other Names:
Drug: oxaliplatin
Given IV
Other Names:
Drug: leucovorin calcium
Given IV
Other Names:
Drug: fluorouracil
Given IV
Other Names:
|
Detailed Description:
PRIMARY OBJECTIVES:
I. To determine if the addition of hedgehog antagonist GDC-0449 (GDC-0449) to FOLFOX chemotherapy improves median progression-free survival (PFS) in the first-line treatment of patients with advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma.
II. To determine the level of baseline hedgehog-pathway activation and correlate with clinical outcome and response to treatment with GDC-0449.
III. To determine a primary gastric cancer gene expression profile that may predict response to GDC-0449.
IV. To determine if serum shed collagen epitopes correlate with clinical outcome and may be used to assess efficacy of GDC-0449 treatment.
V. To determine if circulating endothelial progenitor cells (EPCs) correlate with treatment response and may be used to assess efficacy of GDC-0449 treatment.
VI. To determine if serum expression of VEGF, TGF-β, and IGFBP 3 correlate with clinical outcome and may be used to assess efficacy of GDC-0449 treatment.
SECONDARY OBJECTIVES:
I. To determine if the addition of GDC-0449 to FOLFOX chemotherapy increases overall survival.
II. To determine if the addition of GDC-0449 to FOLFOX chemotherapy increases response rate.
III. To determine if the addition of GDC-0449 to FOLFOX chemotherapy affects toxicity rates.
IV. To assess the hedgehog-pathway expression in those patients who consent to repeat biopsy at week 4-5 and compare to baseline values and clinical outcome.
OUTLINE: This is a multicenter study. Patients are stratified according to institution and disease status (advanced vs metastatic). Patients are randomized to 1 of 2 treatment arms.
ARM I: 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 oral placebo once daily on days 1-14.
ARM II: Patients receive FOLFOX chemotherapy as in arm I. Patients also receive oral hedgehog antagonist GDC-0449 on days 1-14. In both arms, treatment repeats every 2 weeks in the absence of unacceptable toxicity or disease progression.
Tumor tissue and blood samples are collected and analyzed for gene expression and biomarkers.
After completion of study treatment, patients are followed every 3 months.
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Histologically or cytologically confirmed gastric or gastroesophageal junction (GEJ) adenocarcinoma not amenable to surgical resection
- Measurable disease, defined as ≥ 1 lesion that can be accurately measured in ≥ 1 dimension (longest diameter to be recorded) as ≥ 20 mm with conventional techniques or as ≥ 10 mm with spiral CT scan
- Must be willing to provide blood and tissue samples for research purposes
- No known brain metastases
- ECOG performance status (PS) 0-1 or Karnofsky PS 70-100%
- Life expectancy > 3 months
- Absolute neutrophil count ≥ 1,500/mcL
- Platelets ≥ 100,000/mcL
- Total bilirubin ≤ 1.5 times upper limit of normal (ULN)
- AST and ALT ≤ 2.5 times ULN (≤ 5.0 times ULN in the presence of liver metastases)
- Creatinine ≤ 1.5 times ULN OR creatinine clearance ≥ 60 mL/min
- 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 HIV-positive patients
- No other concurrent investigational agents
Contacts and 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 | |
| Decatur Memorial Hospital | |
| Decatur, Illinois, United States, 62526 | |
| Cancer Care Center of Decatur | |
| 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 University Hospital | |
| 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 | |
| Saint Luke's Roosevelt Hospital Center - Saint Luke's Division | |
| New York, New York, United States, 10025 | |
| Beth Israel Medical Center | |
| New York, New York, United States, 10003 | |
| New York University Langone Medical Center | |
| New York, New York, United States, 10016 | |
| Columbia University Medical Center | |
| New York, New York, United States, 10032 | |
| Memorial Sloan Kettering Cancer Center | |
| New York, New York, United States, 10065 | |
| 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 | |
| United States, Pennsylvania | |
| University of Pittsburgh | |
| Pittsburgh, Pennsylvania, United States, 15213 | |
| United States, Tennessee | |
| Vanderbilt University | |
| Nashville, Tennessee, United States, 37232 | |
| United States, Virginia | |
| Virginia Commonwealth University | |
| Richmond, Virginia, United States, 23298 | |
| Principal Investigator: | Deirdre Cohen | New York Cancer Consortium |
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, 09-0356, N01CM00071, N01CM00038, N01CM00070, CDR0000655339 |
| Study First Received: | September 22, 2009 |
| Last Updated: | January 14, 2013 |
| Health Authority: | United States: Food and Drug Administration |
Additional relevant MeSH terms:
|
Stomach Neoplasms Neoplasms, Glandular and Epithelial Neoplasms by Histologic Type Neoplasms Neoplasms, Cystic, Mucinous, and Serous Gastrointestinal Neoplasms Digestive System Neoplasms Neoplasms by Site Hydrocortisone 17-butyrate 21-propionate Hydrocortisone-17-butyrate Adenocarcinoma Adenocarcinoma, Mucinous Carcinoma Digestive System Diseases Gastrointestinal Diseases |
Stomach Diseases Fluorouracil Oxaliplatin Cortisol succinate Hydrocortisone acetate Hydrocortisone Leucovorin Levoleucovorin Antimetabolites Molecular Mechanisms of Pharmacological Action Pharmacologic Actions Antimetabolites, Antineoplastic Antineoplastic Agents Therapeutic Uses Immunosuppressive Agents |
ClinicalTrials.gov processed this record on May 21, 2013