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

This study has been completed.
Sponsor:
Collaborators:
Hoffmann-La Roche
Sanofi
Genentech, Inc.
Information provided by (Responsible Party):
Duke University
ClinicalTrials.gov Identifier:
NCT00447330
First received: March 13, 2007
Last updated: January 28, 2015
Last verified: July 2014
  Purpose

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.


Condition Intervention Phase
Esophageal Neoplasms
Stomach Neoplasms
Neoplasm Metastasis
Drug: capecitabine (Xeloda), oxaliplatin and bevacizumab (Avastin)
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase ll Study of Oxaliplatin, Capecitabine, and Bevacizumab in the Treatment of Metastatic Esophagogastric Adenocarcinomas

Resource links provided by NLM:


Further study details as provided by Duke University:

Primary Outcome Measures:
  • Median Progression-Free Survival (PFS) [ Time Frame: 5 years from study start date ] [ Designated as safety issue: No ]
    Time in months from the start of study treatment to the date of first progression (PD) according to the RECIST criteria, or death due to any cause. PER RECIST, a PD is indicated when there is at least a 20% increase in the sum of the longest diameters from target lesions relative to the smallest sum recorded since treatment is initiated. Median PFS was estimated using a Kaplan-Meier curve, and is the time at which 50% of patients remain alive without disease progression.


Secondary Outcome Measures:
  • 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 ]
    Number of subjects who experienced an adverse event

  • Response Rate [ Time Frame: Every 9 weeks for up to 1 year ] [ Designated as safety issue: No ]
    The proportion of patients for whom the best overall response is complete response (CR) or partial response (PR). A CR occurs when all lesions disappear; whereas, a PR is indicated when there is at least a 30% decrease in the sum of the longest diameters (LD) of the target lesion. A PD (progressive disese) occurs when there is at least a 20% increase in the sum of the LD relative to the smallest sum LD recorded since treatment is initiated. Disease is considered stable if there is no response and no PD. All patients were assigned a best response for inclusion in this calculation in accordance with the protocol.

  • Median Survival [ Time Frame: 5 years after study start date ] [ Designated as safety issue: No ]
    Time in months from the start of study treatment to date of death due to any cause. Median survival was estimated using a Kaplan-Meier curve and is the time point at which 50% of patients remain alive.


Enrollment: 60
Study Start Date: February 2007
Study Completion Date: July 2014
Primary Completion Date: January 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1 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.


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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00447330

Locations
United States, North Carolina
Duke University Medical Center
Durham, North Carolina, United States, 27710
University of Wake Forest Baptist Medical Center
Winston Salem, North Carolina, United States, 27157-0001
Sponsors and Collaborators
Duke University
Hoffmann-La Roche
Sanofi
Genentech, Inc.
Investigators
Principal Investigator: Hope E Uronis, MD Duke University
  More Information

Publications:
Jemal, A., et al., Cancer statistics, 2005. CA Cancer J Clin, 2005. 55(1): p. 10-30.
Sumpter, K., et al. Randomised, mulitcenter phase III study comparing capecitabine with fluorouracil and oxaliplatin with cisplatin in patients with advanced oesophagogastric cancer: confirmation of dose escalation. in Proc Am Soc Clin Onocol. 2003.
Miller, K.D., et al. E2100: A randomized phase III trial of paclitaxel versus paclitaxel plus bevacizumab as first line threapy for locally recurrent or metastatic breast cancer. in American Society for Clinical Oncology. 2005. Orlando, FL.
Goldberg, R.M., et al. N9741: oxaliplatin (Oxal) or CPT-11 + 5-fluorouracil (5FU)/leucovorin (LV) or oxal + CPT-11 in advanced colorectal cancer (CRC). Updated efficacy and quality of life (QOL) data from an intergroup study. in Proc Am Soc Clin Oncol. 2003.
Ishitsuka, H., T. Ishikawa, and Y. Fukase. Capecitabine and the dThdPase up-regulators IFN-gamma or taxol showed synergistic activity in human cancer xenografts. in Proc Am Assoc Cancer Res. 1996.
Hurwitz, H., S.N. Holden, and S.G. Eckhardt, Clinical evaluation of ZD6474, an orally active inhibitor of VEGF signaling in patients with solid tumors. Proceedings of the American Society of Clinical Oncology, 2002. 21: p. Abstract 325.
Brookmeyer, R. and J.J. Crowley, A confidence interval for the median survival time. Biometrics, 1982. 38: p. 29-41.

Responsible Party: Duke University
ClinicalTrials.gov Identifier: NCT00447330     History of Changes
Other Study ID Numbers: Pro00008710, 11100, 8797
Study First Received: March 13, 2007
Results First Received: January 20, 2015
Last Updated: January 28, 2015
Health Authority: United States: Food and Drug Administration

Keywords provided by Duke University:
metastatic esophagogastric adenocarcinomas
ESOPHAGEAL CANCER
GASTRIC CANCER
ADENOCARCINOMA
TARGTED THERAPY
BEVACIZUMAB
CAPECITBAINE
OXALIPLATIN
METASTATIC

Additional relevant MeSH terms:
Adenocarcinoma
Esophageal Neoplasms
Neoplasm Metastasis
Neoplasms
Carcinoma
Digestive System Diseases
Digestive System Neoplasms
Esophageal Diseases
Gastrointestinal Diseases
Gastrointestinal Neoplasms
Head and Neck Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Glandular and Epithelial
Neoplastic Processes
Pathologic Processes
Bevacizumab
Capecitabine
Oxaliplatin
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Growth Inhibitors
Growth Substances
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on March 30, 2015