|Phase II||Biomarker/Laboratory analysis, Treatment||Closed||18 and over||NCI||NCI-2011-01425|
09-0356, CDR0000655339, NYU 09-0356, 8376, N01CM00070, N01CM00071, N01CM00038, P30CA016087, NYCC-09-0356, NCT00982592
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.
Further Study Information
I. To determine if the addition of GDC-0449 to FOLFOX chemotherapy improves median progression free survival (PFS) in the first line treatment of patients with advanced gastric and gastroesophageal junction (GEJ) adenocarcinoma.
I. To determine if the addition of GDC-0449 to FOLFOX chemotherapy affects overall survival.
II. To determine if the addition of GDC-0449 to FOLFOX chemotherapy affects response rate.
III. To determine if the addition of GDC-0449 to FOLFOX chemotherapy affects toxicity rates in the first line treatment of patients with advanced gastric and GEJ adenocarcinoma.
I. To determine the level of baseline hedgehog pathway activation and correlate with clinical outcome and response to treatment with GDC-0449.
II. In those patients who consent to repeat biopsy at week 4-5, hedgehog pathway expression will again be assessed (every attempt will be made to obtain repeat biopsy from the same site as the initial biopsy) and compared to baseline values and clinical outcome.
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 (EPC)'s correlate with treatment response and may be used to assess efficacy of GDC-0449 treatment.
VI. To determine if hedgehog pathway expression is downregulated in EPC's following treatment with GDC-0449.
VII. To determine if serum expression of vascular endothelial growth factor (VEGF), transforming growth factor (TGF)-beta, and insulin-like growth factor binding protein (IGFBP) 3 correlate with clinical outcome and may be used to assess efficacy of GDC-0449 treatment.
VIII. To determine if Her2 expression is predictive in assessing the efficacy of GDC-0449 treatment. Of note, Her2 status will be collected retrospectively for those patients who were tested as part of standard of care established in October 2010.
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 intravenously (IV) over 2 hours, leucovorin calcium IV over 2 hours, and fluorouracil IV over 46-48 hours on day 1. Patients also receive placebo orally (PO) once daily (QD) on days 1-14.
ARM II: Patients receive FOLFOX chemotherapy as in arm I. Patients also receive hedgehog antagonist GDC-0449 PO on days 1-14. In both arms, treatment repeats every 2 weeks in the absence of unacceptable toxicity or disease progression.
After completion of study treatment, patients are followed up every 3 months.
- 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
Trial Lead Organizations/Sponsors
National Cancer Institute
|Deirdre Cohen||Principal Investigator|
|New York Cancer Consortium|
|Deirdre J Cohen||Ph: 212-731-5656|
Link to the current ClinicalTrials.gov record.
NLM Identifer NCT00982592
ClinicalTrials.gov processed this data on October 17, 2013
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