FOLFOX With Bevacizumab in Metastatic or Unresectable Gastroesophageal and Gastric Cancer

Phase II Study of FOLFOX With Bevacizumab (Avastin(TM)) in Metastatic or Unresectable Gastroesophageal and Gastric Cancer

This is a Phase II open-label study to determine the anti-tumor efficacy and tolerability of FOLFOX in combination with bevacizumab (Avastin(TM))in patients with metastatic or unresectable gastroesophageal and gastric adenocarcinoma. Our primary objective is to determine the time to progression in patients treated with FOLFOX in combination with bevacizumab.

Study Overview

• Status: Completed
• Conditions: Gastric Cancer; Gastroesophageal Cancer
• Intervention / Treatment: Drug: FOLFOX; Drug: bevacizumab

• Study Type: Interventional
• Enrollment (Actual): 39
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • Hamden, Connecticut, United States
      • Medical Oncology & Hematology PC
    • New Haven, Connecticut, United States, 06520
      • Yale University School Of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Histologically or cytologically documented recurrent, metastatic or unresectable gastroesophageal (Siewert type I, II, III) or gastric adenocarcinoma with measurable or assessable non-measurable disease (RECIST criteria).
• If recurrent or metastatic disease is not histologically confirmed, then documentation by a second radiographic procedure (i.e., PET scan or MRI in addition to CT scan) is required. If the imaging procedure does not confirm recurrent or metastatic disease, biopsy confirmation is required
• 12 months since completion of any prior neoadjuvant or adjuvant therapy (chemotherapy or radiotherapy) for potentially resectable gastroesophageal or gastric adenocarcinoma.
• >4 weeks since major surgery.
• ECOG Performance Status: 0-1
• Life expectancy >12 weeks
• Laboratory parameters as follows: absolute neutrophil count ≥1,500/uL, platelet count ≥100,000/uL, hemoglobin ≥9 g,/dL, creatinine <1.5 X ULN or estimated GFR >30 ml's/min, urinalysis <2+ protein, baseline proteinuria <1000 mg/d or urine protein/creatinine ratio <1, bilirubin <2 X ULN, PT (INR) <1.5 if patient not on anticoagulation, negative pregnancy test in women of childbearing age
• Hypertension must be well controlled (<160/90)
• Paraffin block or slides must be available
• Patients on full-dose anticoagulants must be on a stable dose of warfarin and have an in-range INR or be on a stable dose of low molecular weight heparin.

Exclusion Criteria:

• prior treatment for recurrent, metastatic, or unresectable gastroesophageal or gastric adenocarcinoma
• other concurrent anticancer therapy
• other malignancy within past three years except basal cell carcinoma of the skin, cervical carcinoma in situ, or nonmetastatic prostate cancer known central nervous system metastases or carcinomatous meningitis.
• interstitial pneumonia or extensive and symptomatic interstitial fibrosis of the lung.
• > grade 2 sensory peripheral neuropathy.
• uncontrolled seizure disorder, active neurological disease, or known CNS disease.
• significant cardiac disease, including the following: unstable angina, New York Heart Association class II-IV congestive heart failure, myocardial infarction within six months prior to study enrollment.
• history of hypertensive crisis or hypertensive encephalopathy
• abdominal fistula, gastrointestinal bleeding, or intra-abdominal abscess within the 6 months prior to study enrollment.
• core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to study enrollment.
• major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to study enrollment or anticipation of need for major surgical procedure during the course of the study.
• recent arterial thrombotic events including stroke or TIA within 6 months prior to study enrollment.
• serious or non-healing wound, ulcer or bone fracture.
• active bleeding or pathological condition that carries a high risk of bleeding (e.g., tumor involving major vessels or known varices).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1; FOLFOX in combination with bevacizumab	Drug: FOLFOX; Oxaliplatin 85/mg/m2 IV infused over two hours followed by Leucovorin 400 mg/m2 IV over 2 hours, followed by 5-FU 400 mg/m2 IV bolus, then 2400 mg/m2 continuous IV infusion over 46-48 hours; Other Names: Eloxatin; Fluorouracil; Drug: bevacizumab; bevacizumab will be used at a dose of 10 mg/kg administered every 2 weeks on day one of FOLFOX chemotherapy; Other Names: Avastin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Progression Free Survival	Upon completion of study, up to 3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Tumor Response Rate by RECIST Criteria	Per response evaulation criteria in solid tumors criteria (RECIST) for target lesions assessed by FDG-PET Scans: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.", or similar definition that is accurate and appropriate.	Upon completion of study
Overall Survival		Upon completion of study, up to 3 years

Collaborators and Investigators

• Sponsor: Yale University
• Collaborators: Genentech, Inc.
• Investigators: Principal Investigator: Jill Lacy, M.D., Yale University

Study record dates

Study Major Dates

• Study Start: May 1, 2008
• Primary Completion (Actual): May 1, 2013
• Study Completion (Actual): July 1, 2014

Study Registration Dates

• First Submitted: May 5, 2008
• First Submitted That Met QC Criteria: May 5, 2008
• First Posted (Estimate): May 7, 2008

Study Record Updates

• Last Update Posted (Estimate): February 4, 2015
• Last Update Submitted That Met QC Criteria: January 21, 2015
• Last Verified: January 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Stomach Diseases; Stomach Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Fluorouracil; Bevacizumab
• Other Study ID Numbers: 0710003118