Esophageal Cancer, Gastric Cancer
Conditions
Keywords
recurrent gastric cancer, stage III gastric cancer, stage IV gastric cancer, recurrent esophageal cancer, stage III esophageal cancer, stage IV esophageal cancer, adenocarcinoma of the stomach
Brief summary
RATIONALE: 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 kill them or carry tumor-killing substances to them. Bevacizumab may also stop the growth of tumor cells by blocking blood flow to the tumor. Drugs used in chemotherapy, such as oxaliplatin and docetaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving bevacizumab together with oxaliplatin and docetaxel may kill more tumor cells. PURPOSE: This phase II trial is studying how well giving bevacizumab together with oxaliplatin and docetaxel works in treating patients with locally advanced unresectable or metastatic stomach or gastroesophageal junction cancer.
Detailed description
OBJECTIVES: Primary * Determine the time to progression in patients with locally advanced unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma treated with bevacizumab, oxaliplatin, and docetaxel. Secondary * Determine the response rate in patients treated with this regimen. * Determine the toxic effects of this regimen in these patients. * Determine time to treatment failure and overall survival of patients treated with this regimen. * Determine the changes in general and disease-specific quality of life, in terms of response to treatment, in patients treated with this regimen. OUTLINE: This is a multicenter study. Patients receive bevacizumab IV over 30-90 minutes, oxaliplatin IV over 120 minutes, and docetaxel IV over 60 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients achieving a complete response (CR) receive 2 additional courses beyond CR. After completion of study treatment, patients are followed periodically for up to 2 years. PROJECTED ACCRUAL: A total of 38 patients will be accrued for this study within 18-23 months.
Interventions
Must be administered 1st before Docetaxel & Oxaliplatin.7.5 mg/kg, IV, day 1 of each cycle; During the first cycle, bevacizumab will be delivered over 90 + or - 15 minutes. If the 1st IV infusion is tolerated w/o infusion-associated adverse events, the 2nd infusion may be delivered over 60 + or - 10 minutes. If the 60 min infusion is well tolerated, all subsequent infusions may be delivered over 30 min + or - 10 mins.
Must be administered 2nd after Bevacizumab and followed by Oxaliplatin.70 mg/m(2), IV over 60 minutes, day 1 of each cycle;
Must be administered 3rd after Bevacizumab and Docetaxel. 75 mg/m(2), IV over 120 minutes, Day 1 of each cycle.
Sponsors
Study design
Eligibility
Inclusion criteria
DISEASE CHARACTERISTICS: * Histologically confirmed gastric or gastroesophageal junction adenocarcinoma * Locally advanced unresectable or metastatic disease * Measurable disease, defined as ≥ 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques OR ≥ 10mm by spiral CT scan * Bone metastases, ascites, or pleural effusions are not considered measurable disease * Evaluable disease must be present outside previously irradiated field * No CNS or brain metastases PATIENT CHARACTERISTICS: Age * 18 and over Performance status * SWOG 0-1 Life expectancy * Not specified Hematopoietic * Absolute neutrophil count ≥ 1,500/mm\^3 * Platelet count ≥ 100,000/mm\^3 * Hemoglobin ≥ 10 mg/dL * No evidence of bleeding diathesis or coagulopathy Hepatic * AST and ALT ≤ 2.5 times upper limit of normal (ULN) * Alkaline phosphatase ≤ 2.5 times ULN * Bilirubin ≤ ULN * INR \< 1.5 Renal * Creatinine \< 2.0 mg/dL * Urine protein:creatinine ratio \< 1.0 Cardiovascular * No history of deep venous thrombosis requiring anticoagulation * No active angina * No myocardial infarction within the past year * No cerebrovascular accident within the past year * No uncontrolled hypertension (systolic blood pressure \[BP\] \> 170 mm Hg and/or diastolic BP \> 100 mm Hg) despite medical management Other * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception during and for 3 months after completion of study treatment * No peripheral neuropathy \> grade 1 * No history of allergy to any of the study drugs or drugs formulated with polysorbate 80 * No known HIV infection * No active peptic ulcer disease * No serious non-healing wound, ulcer, or bone fracture * No unresolved bacterial infection requiring antibiotics * No other active malignancy within the past 3 years except for cancers that have been treated with a curative intent PRIOR CONCURRENT THERAPY: Biologic therapy * No concurrent immunotherapy Chemotherapy * No prior chemotherapy for gastric cancer unless disease relapsed \> 6 months after completion of non-taxane adjuvant chemotherapy * No other concurrent chemotherapy Endocrine therapy * Not specified Radiotherapy * See Disease Characteristics * At least 3 weeks since radiotherapy Surgery * At least 4 weeks since prior surgery or open biopsy (except indwelling venous catheter placement) * No concurrent surgery Other * At least 4 weeks since prior and no concurrent participation in another experimental drug trial * No concurrent full-dose anticoagulation * No concurrent experimental drugs
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to Progression | After every 2 cycles (1 cycle =21 days) From study registration until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 18 months | Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Response Rate by RECIST Criteria | After every 2 cycles (1 cycle =21 days) | Percentage of Participants with response by RECIST criteria until progression |
| Toxicity Profile | At 21 days following completion of study treatment | Toxicity profile of grade 3 and grade 4 events using the NCI-CTCAE Version 3.0 scale for toxicity grading. |
| Time to Treatment Failure | Every 21 days From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months | Time to treatment failure using the Kaplan-Meier method |
| Overall Survival | Patients will be followed for survival every three months after they are off study or until their disease progresses, for up to two years | Overall survival using the Kaplan-Meier method |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Docetaxel, Oxaliplatin & Bevacizumab Must be administered 1st before Docetaxel & Oxaliplatin.7.5 mg/kg, IV, day 1 of each cycle; During the first cycle, bevacizumab will be delivered over 90 + or - 15 minutes. If the 1st IV infusion is tolerated w/o infusion-associated adverse events, the 2nd infusion may be delivered over 60 + or - 10 minutes. If the 60 min infusion is well tolerated, all subsequent infusions may be delivered over 30 min + or - 10 mins.
Bevacizumab: Must be administered 1st before Docetaxel & Oxaliplatin.7.5 mg/kg, IV, day 1 of each cycle; During the first cycle, bevacizumab will be delivered over 90 + or - 15 minutes. If the 1st IV infusion is tolerated w/o infusion-associated adverse events, the 2nd infusion may be delivered over 60 + or - 10 minutes. | 39 |
| Total | 39 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Docetaxel, Oxaliplatin & Bevacizumab |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 11 Participants |
| Age, Categorical Between 18 and 65 years | 28 Participants |
| Region of Enrollment United States | 39 Participants |
| Sex: Female, Male Female | 10 Participants |
| Sex: Female, Male Male | 29 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 23 / 39 |
| serious Total, serious adverse events | 23 / 39 |
Outcome results
Time to Progression
Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions
Time frame: After every 2 cycles (1 cycle =21 days) From study registration until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 18 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Docetaxel, Oxaliplatin & Bevacizumab | Time to Progression | 6.6 months |
Overall Survival
Overall survival using the Kaplan-Meier method
Time frame: Patients will be followed for survival every three months after they are off study or until their disease progresses, for up to two years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Docetaxel, Oxaliplatin & Bevacizumab | Overall Survival | 11.1 months |
Response Rate by RECIST Criteria
Percentage of Participants with response by RECIST criteria until progression
Time frame: After every 2 cycles (1 cycle =21 days)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Docetaxel, Oxaliplatin & Bevacizumab | Response Rate by RECIST Criteria | 42 percentage of responders |
Time to Treatment Failure
Time to treatment failure using the Kaplan-Meier method
Time frame: Every 21 days From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Docetaxel, Oxaliplatin & Bevacizumab | Time to Treatment Failure | 4.5 months |
Toxicity Profile
Toxicity profile of grade 3 and grade 4 events using the NCI-CTCAE Version 3.0 scale for toxicity grading.
Time frame: At 21 days following completion of study treatment
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Docetaxel, Oxaliplatin & Bevacizumab | Toxicity Profile | Nausea | 4 Participants |
| Docetaxel, Oxaliplatin & Bevacizumab | Toxicity Profile | Vomiting | 2 Participants |
| Docetaxel, Oxaliplatin & Bevacizumab | Toxicity Profile | TE Fistula | 1 Participants |
| Docetaxel, Oxaliplatin & Bevacizumab | Toxicity Profile | Hypertension | 2 Participants |
| Docetaxel, Oxaliplatin & Bevacizumab | Toxicity Profile | Venous Thromboemblism | 1 Participants |
| Docetaxel, Oxaliplatin & Bevacizumab | Toxicity Profile | Neutropenia | 13 Participants |
| Docetaxel, Oxaliplatin & Bevacizumab | Toxicity Profile | Leukopenia | 1 Participants |
| Docetaxel, Oxaliplatin & Bevacizumab | Toxicity Profile | GI Perforation | 3 Participants |
| Docetaxel, Oxaliplatin & Bevacizumab | Toxicity Profile | Neuropathy | 5 Participants |
| Docetaxel, Oxaliplatin & Bevacizumab | Toxicity Profile | Diarrhea | 3 Participants |
| Docetaxel, Oxaliplatin & Bevacizumab | Toxicity Profile | Dehydration | 4 Participants |
| Docetaxel, Oxaliplatin & Bevacizumab | Toxicity Profile | Fever | 2 Participants |
| Docetaxel, Oxaliplatin & Bevacizumab | Toxicity Profile | Fatigue | 2 Participants |
| Docetaxel, Oxaliplatin & Bevacizumab | Toxicity Profile | Anorexia | 2 Participants |