Overview

This trial is active, not recruiting.

Conditions esophageal neoplasms, stomach neoplasms, neoplasm metastasis
Treatment capecitabine (xeloda), oxaliplatin and bevacizumab (avastin)
Phase phase 2
Sponsor Duke University
Collaborator Hoffmann-La Roche
Start date February 2007
End date January 2014
Trial size 37 participants
Trial identifier NCT00447330, 11100, 8797, Pro00008710

Summary

The purpose of this study is to evaluate the progression free survival of capecitabine (Xeloda), oxaliplatin and bevacizumab (Avastin) in previously untreated metastatic esophagogastric adenocarcinomas.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation non-randomized
Endpoint classification safety/efficacy study
Intervention model single group assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
capecitabine (xeloda), oxaliplatin and bevacizumab (avastin)
Capecitabine will be administered orally at a twice daily dose of 850 mg/m2 (equivalent to a total daily dose of 1700 mg/m2) given days 1-14 of the three week cycle. Oxaliplatin will be administered at the dose of 130 mg/m2 given as a 2-hour intravenous infusion on day 1 of a three week cycle. Bevacizumab will be administered at a dose of 15 mg/kg given as a 30-90 minute intravenous infusion on day 1 of a three week cycle following the administration of oxaliplatin.

Primary Outcomes

Measure
To evaluate the progression free survival (PFS) of the combination of bevacizumab, oxaliplatin and capecitabine in patients with previously untreated metastatic esophagogastric adenocarcinoma
time frame: 2+ years from study start date

Secondary Outcomes

Measure
To assess the safety and tolerability of the combination of bevacizumab, oxaliplatin and capecitabine in patients with previously untreated metastatic esophagogastric adenocarcinoma
time frame: Every 21 days
To assess response rate (RR) in patients treated with the combination
time frame: Every 9 weeks
To preliminarily assess overall survival (OS) in patients treated with the combination
time frame: 2 years after study start date
To evaluate the effect of the combination therapy on blood based biomarkers of angiogenesis
time frame: Biomarker cycle days 1 and 8 and 15
To assess the effect of the bevacizumab monotherapy on tumor and wound angiogenesis, using Immunoblotting, ELISA, and mRNA expression analyses
time frame: 2 years after study start date

Eligibility Criteria

Male or female participants at least 18 years old.

Primary Inclusion Criteria: - Histologically or cytologically documented and radiographically measurable adenocarcinoma of the esophagus or stomach that is metastatic/recurrent and not amenable to potentially curative treatment - No prior therapy for metastatic disease - Prior radiation therapy is permitted, provided it is completed > 28 days prior to day 1 of study drug - Normal organ and marrow function - Karnofsky Performance Status 70-100% Primary Exclusion Criteria: - Unstable or poorly controlled hypertension > 150/100 mm Hg - Arterial thromboembolic events within 6 months - Clinically significant uncontrolled cardiac disease - Significant proteinuria at baseline - Grade 2 or greater peripheral neuropathy - History of abdominal fistula, GI perforation, or intra-abdominal abscess within 6 months

Additional Information

Official title A Phase ll Study of Oxaliplatin, Capecitabine, and Bevacizumab in the Treatment of Metastatic Esophagogastric Adenocarcinomas
Principal investigator Hope E Uronis, MD
Description The number of new cases of esophageal and gastric cancers in the United States in 2005 is 14520 for esophageal cancer and 21860 for gastric cancer. Unfortunately, esophageal and gastric cancers will also account for 13570 and 11550 deaths, respectively, in 2005. The 5 year survival rates for metastatic gastroesophageal, GE junctional, and gastric cancers are less than 5%. The major current treatment modality for patients with advanced esophageal, GE junctional, and gastric adenocarcinomas is systemic chemotherapy. We seek to investigate the efficacy of capecitabine and oxaliplatin in combination with bevacizumab as first line treatment for metastatic esophagogastric cancers. The choice of capecitabine and oxaliplatin is made to develop a user-friendly biologically-based regimen, offering patients oral capecitabine in place of continuous 5FU infusion pumps. Since capecitabine can be given crushed this regimen may both be active and user-friendly. Preliminary data in colorectal cancer suggest that the regimen of capecitabine, oxaliplatin, and bevacizumab has comparable activity to FOLFOX-bevacizumab. The goal of the proposed regimen is to define a capecitabine and oxaliplatin-based regimen that optimizes biological approaches over cytotoxic approaches. The addition of bevacizumab to chemotherapy regimens for metastatic colorectal cancer, metastatic non-small cell lung cancer, and metastatic breast cancer has shown to improve response rates and overall survival. If active, this regimen could serve as a first line comparator to the capecitabine, oxaliplatin, and epirubicin combination. This approach will also help to simplify regimen development across gastrointestinal cancers. In addition to the primary efficacy endpoint of this protocol, several correlative endpoints will also be examined in an exploratory manner. The importance of developing blood-based and tumor biomarkers has been extensively reviewed. However, the role of such predictive markers has not been well studied for XELOX-A. This information is important since it may help define which populations are most likely to benefit and most likely to suffer significant toxicity from this important GI cancer regimen. This biomarker approach may also help understand and define mechanisms of sensitivity, resistance, and toxicity that may be used to guide future hypothesis-driven studies designed to improve the efficacy and safety of this regimen. The correlative biomarker endpoints include serum, plasma and urine biomarkers (e.g. VEGF and bFGF), a wound healing model of angiogenesis, and tumor biopsy studies .
Trial information was received from ClinicalTrials.gov and was last updated in July 2014.
Information provided to ClinicalTrials.gov by Duke University.