Oxaliplatin, Capecitabine and Avastin for Metastatic Esophagogastric Adenocarcinoma (XAGastric)

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Hoffmann-La Roche
Sanofi
Genentech
Information provided by (Responsible Party):
Duke University
ClinicalTrials.gov Identifier:
NCT00447330
First received: March 13, 2007
Last updated: July 11, 2014
Last verified: July 2014

March 13, 2007
July 11, 2014
February 2007
January 2014   (final data collection date for primary outcome 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 ] [ Designated as safety issue: No ]
Disease response assessed by CT/MRI every 9 weeksusing RECIST criteria.
Complete list of historical versions of study NCT00447330 on ClinicalTrials.gov Archive Site
  • 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 ] [ Designated as safety issue: Yes ]
  • To assess response rate (RR) in patients treated with the combination [ Time Frame: Every 9 weeks ] [ Designated as safety issue: No ]
  • To preliminarily assess overall survival (OS) in patients treated with the combination [ Time Frame: 2 years after study start date ] [ Designated as safety issue: No ]
  • To evaluate the effect of the combination therapy on blood based biomarkers of angiogenesis [ Time Frame: Biomarker cycle days 1 and 8 and 15 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
Not Provided
Not Provided
Not Provided
 
Oxaliplatin, Capecitabine and Avastin for Metastatic Esophagogastric Adenocarcinoma
A Phase ll Study of Oxaliplatin, Capecitabine, and Bevacizumab in the Treatment of Metastatic Esophagogastric Adenocarcinomas

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.

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 .

Interventional
Phase 2
Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Esophageal Neoplasms
  • Stomach Neoplasms
  • Neoplasm Metastasis
Drug: 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.

Experimental: 1
Intervention: Drug: capecitabine (Xeloda), oxaliplatin and bevacizumab (Avastin)

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
37
January 2015
January 2014   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00447330
Pro00008710, 11100, 8797
Yes
Duke University
Duke University
  • Hoffmann-La Roche
  • Sanofi
  • Genentech
Principal Investigator: Hope E Uronis, MD Duke University
Duke University
July 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP