Gastric Cancer, Gastroesophageal Cancer
Conditions
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.
Interventions
DRUGFOLFOX
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
DRUGbevacizumab
bevacizumab will be used at a dose of 10 mg/kg administered every 2 weeks on day one of FOLFOX chemotherapy
Sponsors
Genentech, Inc.
Yale University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Progression Free Survival | Upon completion of study, up to 3 years |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| Overall Survival | Upon completion of study, up to 3 years | — |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| FOLFOX/Bevacizumab Administration 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 | 39 |
| Total | 39 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 4 |
| Overall Study | Investigators' discretion | 2 |
| Overall Study | Progressive disease | 27 |
| Overall Study | Withdrawal by Subject | 3 |
Baseline characteristics
| Characteristic | FOLFOX/Bevacizumab Administration |
|---|---|
| Age, Continuous | 62 years |
| Sex: Female, Male Female | 8 Participants |
| Sex: Female, Male Male | 31 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 16 / 39 |
| serious Total, serious adverse events | 4 / 39 |
Outcome results
Primary
Progression Free Survival
Time frame: Upon completion of study, up to 3 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| FOLFOX/Bevacizumab Administration | Progression Free Survival | 7.8 months |
Secondary
Overall Survival
Time frame: Upon completion of study, up to 3 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| FOLFOX/Bevacizumab Administration | Overall Survival | 14.7 months |
Secondary
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.
Time frame: Upon completion of study
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| FOLFOX/Bevacizumab Administration | Overall Tumor Response Rate by RECIST Criteria | 56.4 percentage of participants |