FOLFOX With Bevacizumab in Metastatic or Unresectable Gastroesophageal and Gastric Cancer

• Sponsor: Yale University (Other)
• Overall Status: Completed
• CT.gov ID: NCT00673673
• Collaborator: Genentech, Inc. (Industry)
• Enrollment: 39
• Locations: 2
• Arm: 1
• Duration (Months): 74
• Patients Per Site: 19.5
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Gastroesophageal Cancer; Gastric Cancer	Drug: FOLFOX; Drug: bevacizumab	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 39 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Study of FOLFOX With Bevacizumab (Avastin(TM)) in Metastatic or Unresectable Gastroesophageal and Gastric Cancer
• Study Start Date: May 1, 2008
• Actual Primary Completion Date: May 1, 2013
• Actual Study Completion Date: Jul 1, 2014

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Progression Free Survival [Upon completion of study, up to 3 years]

Secondary Outcome Measures

1. Overall Tumor Response Rate by RECIST Criteria [Upon completion of study]

   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.

2. Overall Survival [Upon completion of study, up to 3 years]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Medical Oncology & Hematology PC	Hamden	Connecticut	United States
2	Yale University School of Medicine	New Haven	Connecticut	United States	06520

Sponsors and Collaborators

• Yale University
• Genentech, Inc.

Investigators

• Principal Investigator: Jill Lacy, M.D., Yale University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Yale University
• ClinicalTrials.gov Identifier: NCT00673673
• Other Study ID Numbers: 0710003118
• First Posted: May 7, 2008
• Last Update Posted: Feb 4, 2015
• Last Verified: Jan 1, 2015

• Additional relevant MeSH terms: Stomach Neoplasms; Bevacizumab; Fluorouracil

Study Results

Participant Flow

Arm/Group Title	FOLFOX/Bevacizumab Administration
Arm/Group Description	FOLFOX in combination with bevacizumab 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 bevacizumab: bevacizumab will be used at a dose of 10 mg/kg administered every 2 weeks on day one of FOLFOX chemotherapy
Period Title: Overall Study
STARTED	39
COMPLETED	3
NOT COMPLETED	36

Baseline Characteristics

Arm/Group Title	FOLFOX/Bevacizumab Administration
Arm/Group Description	FOLFOX in combination with bevacizumab 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 bevacizumab: bevacizumab will be used at a dose of 10 mg/kg administered every 2 weeks on day one of FOLFOX chemotherapy
Overall Participants	39
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	62
Sex: Female, Male (Count of Participants)
Female	8 20.5%
Male	31 79.5%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	FOLFOX/Bevacizumab Administration
Arm/Group Description	FOLFOX in combination with bevacizumab 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 bevacizumab: bevacizumab will be used at a dose of 10 mg/kg administered every 2 weeks on day one of FOLFOX chemotherapy
Measure Participants	39
Median (95% Confidence Interval) [months]	7.8

2. Secondary Outcome

Title	Overall Tumor Response Rate by RECIST Criteria
Description	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.
Time Frame	Upon completion of study

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	FOLFOX/Bevacizumab Administration
Arm/Group Description	FOLFOX in combination with bevacizumab 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 bevacizumab: bevacizumab will be used at a dose of 10 mg/kg administered every 2 weeks on day one of FOLFOX chemotherapy
Measure Participants	39
Number [percentage of participants]	56.4 144.6%

3. Secondary Outcome

Title	Overall Survival
Time Frame	Upon completion of study, up to 3 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	FOLFOX/Bevacizumab Administration
Arm/Group Description	FOLFOX in combination with bevacizumab 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 bevacizumab: bevacizumab will be used at a dose of 10 mg/kg administered every 2 weeks on day one of FOLFOX chemotherapy
Measure Participants	39
Median (95% Confidence Interval) [months]	14.7

Adverse Events

Time Frame	Toxicity assessment were performed up to 3 years
Arm/Group Title	FOLFOX/Bevacizumab Administration
Arm/Group Description	FOLFOX in combination with bevacizumab 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 bevacizumab: bevacizumab will be used at a dose of 10 mg/kg administered every 2 weeks on day one of FOLFOX chemotherapy
All Cause Mortality
	FOLFOX/Bevacizumab Administration
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	FOLFOX/Bevacizumab Administration
	Affected / at Risk (%)	# Events
Total	4/39 (10.3%)
Blood and lymphatic system disorders
Thromboytopenia	2/39 (5.1%)
Nervous system disorders
Neuropathy	1/39 (2.6%)
Renal and urinary disorders
Proteinuria	1/39 (2.6%)
Other (Not Including Serious) Adverse Events
	FOLFOX/Bevacizumab Administration
	Affected / at Risk (%)	# Events
Total	16/39 (41%)
Blood and lymphatic system disorders
Anemia	1/39 (2.6%)
Neurtropenia	11/39 (28.2%)
Thrombocytopenia	2/39 (5.1%)
Gastrointestinal disorders
Mucositis	1/39 (2.6%)
Dysphagia	1/39 (2.6%)
Diarrhea	3/39 (7.7%)
Abdominal Pain	4/39 (10.3%)
General disorders
Fatigue	3/39 (7.7%)
Electrolytes Imbalence	2/39 (5.1%)
Hepatobiliary disorders
Abnormal Liver Function Tests	3/39 (7.7%)
Nervous system disorders
Neuropathy	8/39 (20.5%)
Renal and urinary disorders
Proteinuria	1/39 (2.6%)
Respiratory, thoracic and mediastinal disorders
Dyspnea	2/39 (5.1%)
Skin and subcutaneous tissue disorders
Hand-Foot Syndrome	1/39 (2.6%)
Vascular disorders
Deep Vein Thrombosis/Pulmonary Embolism	3/39 (7.7%)
Hypertension	1/39 (2.6%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.