Clinical trial NCT00447330: Oxaliplatin, Capecitabine and Avastin for Metastatic Esophagogastric Adenocarcinoma
Official title: A Phase ll Study of Oxaliplatin, Capecitabine, and Bevacizumab in the Treatment of Metastatic Esophagogastric Adenocarcinomas
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Esophageal Neoplasms
Stomach Neoplasms
Neoplasm Metastasis
Keywords: metastatic esophagogastric adenocarcinomas
ESOPHAGEAL CANCER
GASTRIC CANCER
ADENOCARCINOMA
TARGTED THERAPY
BEVACIZUMAB
CAPECITBAINE
OXALIPLATIN
METASTATIC
Lead sponsor: Duke University
Sponsor class: OTHER
Collaborators: name: Hoffmann-La Roche
name: Sanofi
name: Genentech, Inc.
First posted: 2007-03-14
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

Detailed 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 .

Eligibility criteria: 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

Primary outcomes:
measure: Median Progression-Free Survival (PFS)
timeFrame: 5 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
timeFrame: Every 21 days
measure: Response Rate
timeFrame: Every 9 weeks for up to 1 year
measure: Median Survival
timeFrame: 5 years after study start date
Other outcomes:
Locations:
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Winston Salem
country: United States
facility: University of Wake Forest Baptist Medical Center
state: North Carolina
Study officials:
affiliation: Duke University
name: Hope E Uronis, MD
role: PRINCIPAL_INVESTIGATOR
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