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Bevacizumab and Combination Chemotherapy Before Surgery in Treating Patients With Locally Advanced Esophageal or Stomach Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2014 by Fox Chase Cancer Center
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Fox Chase Cancer Center
ClinicalTrials.gov Identifier:
NCT01212822
First received: September 29, 2010
Last updated: March 17, 2014
Last verified: March 2014
  Purpose

This pilot phase II trial studies how well giving bevacizumab and combination chemotherapy together before surgery works in treating patients with locally advanced esophageal or stomach cancer. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Drugs used in chemotherapy, such as leucovorin calcium, fluorouracil, and oxaliplatin work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving bevacizumab and combination chemotherapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Giving these treatments after surgery may kill any tumor cells that remain after surgery.


Condition Intervention Phase
Adenocarcinoma of the Esophagus
Adenocarcinoma of the Gastroesophageal Junction
Diffuse Adenocarcinoma of the Stomach
Intestinal Adenocarcinoma of the Stomach
Mixed Adenocarcinoma of the Stomach
Squamous Cell Carcinoma of the Esophagus
Stage IA Esophageal Cancer
Stage IA Gastric Cancer
Stage IB Esophageal Cancer
Stage IB Gastric Cancer
Stage IIA Esophageal Cancer
Stage IIA Gastric Cancer
Stage IIB Esophageal Cancer
Stage IIB Gastric Cancer
Stage IIIA Esophageal Cancer
Stage IIIA Gastric Cancer
Stage IIIB Esophageal Cancer
Stage IIIB Gastric Cancer
Stage IIIC Esophageal Cancer
Stage IIIC Gastric Cancer
Biological: bevacizumab
Drug: oxaliplatin
Drug: leucovorin calcium
Drug: fluorouracil
Procedure: therapeutic conventional surgery
Other: laboratory biomarker analysis
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Trial of Pre-operative Bevacizumab and FOLFOX Chemotherapy in Locally Advanced Esophageal Cancer

Resource links provided by NLM:


Further study details as provided by Fox Chase Cancer Center:

Primary Outcome Measures:
  • Disease-free survival [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Complete and partial response to neoadjuvant therapy based on the Response Evaluation Criteria in Solid Tumors (RECIST) [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
    Characterized using proportions and 95% confidence intervals.

  • Overall survival [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
    Characterized using Kaplan-Meier curves.

  • Progression free survival [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
    Characterized using Kaplan-Meier curves.

  • Incidence of toxicities, using the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version (v)4.0 [ Time Frame: Up to 6 weeks after final treatment ] [ Designated as safety issue: Yes ]
    Characterized using means, standard deviations, proportions, and 95% confidence intervals.

  • Change in biomarker levels [ Time Frame: Baseline up to day of surgery ] [ Designated as safety issue: Yes ]
    Means, medians, and standard deviations of the biomarker levels and change in biomarker levels within groups defined by response/resistance outcomes will be reported.


Estimated Enrollment: 39
Study Start Date: April 2011
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (bevacizumab, FOLFOX)

NEOADJUVANT THERAPY: Patients receive bevacizumab IV over 30-90 minutes on day 1. Patients also receive FOLFOX chemotherapy comprising oxaliplatin IV over 2 hours and leucovorin calcium IV over 2 hours on day 1, and fluorouracil IV continuously over 46 hours on days 1-2. Treatment with bevacizumab repeats every 2 weeks for 4 courses and treatment with FOLFOX repeats every 2 weeks for 6 courses in the absence of disease progression or unacceptable toxicity.

SURGERY: Patients then undergo planned surgical resection 4-6 weeks after 6 courses of chemotherapy and at least 8 weeks since the last dose of bevacizumab.

ADJUVANT THERAPY: Beginning 8-10 weeks after surgery, patients receive bevacizumab IV, oxaliplatin IV, leucovorin calcium IV, and fluorouracil IV as in neoadjuvant therapy. Treatment repeats every 2 weeks for 6 courses in the absence of disease progression or unacceptable toxicity.

Biological: bevacizumab
Given IV
Other Names:
  • anti-VEGF humanized monoclonal antibody
  • anti-VEGF monoclonal antibody
  • Avastin
  • rhuMAb VEGF
Drug: oxaliplatin
Given IV
Other Names:
  • 1-OHP
  • Dacotin
  • Dacplat
  • Eloxatin
  • L-OHP
Drug: leucovorin calcium
Given IV
Other Names:
  • CF
  • CFR
  • LV
Drug: fluorouracil
Given IV
Other Names:
  • 5-fluorouracil
  • 5-Fluracil
  • 5-FU
Procedure: therapeutic conventional surgery
Undergo surgical resection
Other: laboratory biomarker analysis
Correlative studies

Detailed Description:

PRIMARY OBJECTIVES:

I. To investigate two-year disease-free survival in patients with resectable esophageal and gastroesophageal (GE) junction cancer treated with perioperative bevacizumab and leucovorin calcium, fluorouracil, and oxaliplatin (FOLFOX).

SECONDARY OBJECTIVES:

I. To assess, by pathological examination after surgical resection, complete and partial response to neoadjuvant therapy.

II. To characterize overall and progression free survival. III. To compare baseline and post-chemotherapy/bevacizumab tissues for biomarkers predicting response or resistance to this approach.

IV. To investigate safety in this setting.

OUTLINE:

NEOADJUVANT THERAPY: Patients receive bevacizumab intravenously (IV) over 30-90 minutes on day 1. Patients also receive FOLFOX chemotherapy comprising oxaliplatin IV over 2 hours and leucovorin calcium IV over 2 hours on day 1, and fluorouracil IV continuously over 46 hours on days 1-2. Treatment with bevacizumab repeats every 2 weeks for 4 courses and treatment with FOLFOX repeats every 2 weeks for 6 courses in the absence of disease progression or unacceptable toxicity.

SURGERY: Patients then undergo planned surgical resection 4-6 weeks after 6 courses of chemotherapy and at least 8 weeks since the last dose of bevacizumab.

ADJUVANT THERAPY: Beginning 8-10 weeks after surgery, patients receive bevacizumab IV, oxaliplatin IV, leucovorin calcium IV, and fluorouracil IV as in neoadjuvant therapy. Treatment repeats every 2 weeks for 6 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 4 months for 1 year, every 6 months for 2 years, and then annually thereafter.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients must have biopsy proven adenocarcinoma, squamous cell carcinoma or undifferentiated carcinoma of the esophagus, GE junction and/or gastric cardia
  • Patients must have potentially resectable disease by the thoracic, minimally invasive or transhiatal approach

    • No portion of the lesion may be within 5 cm of the cricopharyngeus
    • Patient must be considered medically fit for surgery with average or below average risk
    • T1-3 or T4 with local invasion confined to diaphragm, pleura or pericardium
    • No myocardial infarction within 12 months of enrollment
  • Patients must have Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
  • White blood cells (WBC) >= 3,500/mm^3
  • Platelet count >= 100,000/mm^3
  • Serum creatinine (Cr) =< 1.5 mg and/or creatinine clearance >= 60 cc/min
  • Bilirubin must be < upper limit of normal (ULN) unless the patient has a chronic grade 1 bilirubin elevation due to Gilbert's disease or similar syndrome due to slow conjugation of bilirubin
  • Alkaline phosphatase must be < ULN
  • Aspartate aminotransferase (AST) & alanine aminotransferase (ALT) must be < ULN
  • Urine protein/creatinine (UPC) ratio of < 1.0 or dipstick for protein of < 2+, Common Terminology Criteria for Adverse Events version 4.0 (CTCAE v 4) grade < 2; patients with a UPC ratio >= 1.0 or dipstick of 2+ must undergo a 24-hour urine collection and must demonstrate < 1 gm of protein in order to participate
  • Patients must give written informed consent and Health Insurance Portability and Accountability Act (HIPAA) consent

Exclusion Criteria:

  • Patients with prior chemotherapy for any malignant disorder, thoracic radiotherapy or prior surgical resection of an esophageal tumor are ineligible
  • Patients with biopsy-proven invasion of the tracheobronchial tree or tracheo-esophageal fistula are ineligible
  • Patients with a history of a curatively treated malignancy must be disease-free for at least two years and have a survival prognosis that is greater than five years
  • Eligible patients of reproductive potential (both sexes) must agree to use an accepted and effective method of contraceptive during study therapy and for at least 6 months after the completion of bevacizumab; women must not be pregnant or breast-feeding because the study drugs administered may cause harm to an unborn fetus or breastfeeding child; all females of childbearing potential must have a serum pregnancy test to rule out pregnancy within 7 days prior to registration
  • Patients with a history of hypertension must measure < 150/90 mmHg and be on a stable regimen of anti-hypertensive therapy; patients with a history of hypertension who have a blood pressure of 150/90 mmHg, or greater are not eligible; patients with a history of hypertension who have a blood pressure of < 150/90 mmHg but are not on a stable regimen of anti-hypertensive therapy, are not eligible
  • Any prior history of hypertensive crisis or hypertensive encephalopathy
  • New York Association (NYHA) grade II or greater congestive heart failure
  • Patients must not have a serious or non-healing wound, skin ulcers or unhealed bone fracture, or known human immunodeficiency virus (HIV) infection
  • Patients with >= grade 2 neuropathy are not eligible
  • Patients must not have had significant traumatic injury within 28 days prior to randomization
  • Patients with PT (INR) > 1.5 are not eligible; the patient may not be receiving full-dose anticoagulation; prophylactic or full dose anticoagulation are permitted post-resection or for treatment of an intercurrent thrombotic event
  • Patients with non-malignant systemic disease (cardiovascular, renal, hepatic, etc.) that would preclude any of the study therapy drugs are not eligible; specifically excluded are the following conditions: current symptomatic arrhythmia, symptomatic peripheral vascular disease
  • Patients with a history of the following within 12 months of study entry are not eligible: arterial thromboembolic events, unstable angina
  • Any history of stroke or transient ischemic attack
  • Significant vascular disease (i.e. aortic dissection, aortic aneurysm)
  • Patients with psychiatric or addictive disorders or other conditions that, in the opinion of the investigator, would preclude them from meeting the study requirements are not eligible
  • Distant metastases
  • History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to study enrollment
  • Known hypersensitivity to any component of bevacizumab
  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: NCT01212822

Locations
United States, Ohio
Case Western Reserve University Not yet recruiting
Cleveland, Ohio, United States, 44106
Contact: Michael K. Gibson    216-844-5220    michael.gibson@uhhospitals.org   
Principal Investigator: Michael K. Gibson         
United States, Pennsylvania
Fox Chase Cancer Center Recruiting
Philadelphia, Pennsylvania, United States, 19111-2497
Contact: Crystal Denlinger, MD    215-214-1676    crystal.denlinger@fccc.edu   
Principal Investigator: Crystal Denlinger, MD         
University of Pittsburgh Cancer Institute Recruiting
Pittsburgh, Pennsylvania, United States, 15232
Contact: Weijing Sun    412-831-9748      
Principal Investigator: Weijing Sun, MD         
Sponsors and Collaborators
Fox Chase Cancer Center
Investigators
Principal Investigator: Barbara Burtness Fox Chase Cancer Center
  More Information

No publications provided

Responsible Party: Fox Chase Cancer Center
ClinicalTrials.gov Identifier: NCT01212822     History of Changes
Other Study ID Numbers: FER-GI-029, NCI-2013-00603, IRB#10-022, FER-GI-029, P30CA006927
Study First Received: September 29, 2010
Last Updated: March 17, 2014
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Adenocarcinoma
Carcinoma, Squamous Cell
Esophageal Neoplasms
Stomach Neoplasms
Carcinoma
Digestive System Diseases
Digestive System Neoplasms
Esophageal Diseases
Gastrointestinal Diseases
Gastrointestinal Neoplasms
Head and Neck Neoplasms
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Glandular and Epithelial
Neoplasms, Squamous Cell
Stomach Diseases
Antibodies
Antibodies, Monoclonal
Bevacizumab
Fluorouracil
Leucovorin
Levoleucovorin
Oxaliplatin
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Antidotes
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents

ClinicalTrials.gov processed this record on November 27, 2014