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Bevacizumab, Oxaliplatin, and Docetaxel in Treating Patients With Locally Advanced Unresectable or Metastatic Stomach or Gastroesophageal Junction Cancer

Phase II Trial of Bevacizumab, Docetaxel, and Oxaliplatin in Gastric and Gastroesophageal Junction Cancer

Status
Completed
Phases
Phase 2
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT00217581
Enrollment
39
Registered
2005-09-22
Start date
2004-10-31
Completion date
2013-01-31
Last updated
2019-03-26

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Esophageal Cancer, Gastric Cancer

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

BIOLOGICALBevacizumab

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.

DRUGDocetaxel

Must be administered 2nd after Bevacizumab and followed by Oxaliplatin.70 mg/m(2), IV over 60 minutes, day 1 of each cycle;

DRUGOxaliplatin

Must be administered 3rd after Bevacizumab and Docetaxel. 75 mg/m(2), IV over 120 minutes, Day 1 of each cycle.

Sponsors

National Cancer Institute (NCI)
CollaboratorNIH
Barbara Ann Karmanos Cancer Institute
Lead SponsorOTHER

Study design

Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE

Eligibility

Sex/Gender
ALL
Age
18 Years to 120 Years
Healthy volunteers
No

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

MeasureTime frameDescription
Time to ProgressionAfter 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 monthsProgression 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

MeasureTime frameDescription
Response Rate by RECIST CriteriaAfter every 2 cycles (1 cycle =21 days)Percentage of Participants with response by RECIST criteria until progression
Toxicity ProfileAt 21 days following completion of study treatmentToxicity profile of grade 3 and grade 4 events using the NCI-CTCAE Version 3.0 scale for toxicity grading.
Time to Treatment FailureEvery 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 monthsTime to treatment failure using the Kaplan-Meier method
Overall SurvivalPatients will be followed for survival every three months after they are off study or until their disease progresses, for up to two yearsOverall survival using the Kaplan-Meier method

Countries

United States

Participant flow

Participants by arm

ArmCount
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
Total39

Withdrawals & dropouts

PeriodReasonFG000
Overall StudyWithdrawal by Subject1

Baseline characteristics

CharacteristicDocetaxel, 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 typeEG000
affected / at risk
deaths
Total, all-cause mortality
— / —
other
Total, other adverse events
23 / 39
serious
Total, serious adverse events
23 / 39

Outcome results

Primary

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

ArmMeasureValue (MEDIAN)
Docetaxel, Oxaliplatin & BevacizumabTime to Progression6.6 months
Secondary

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

ArmMeasureValue (MEDIAN)
Docetaxel, Oxaliplatin & BevacizumabOverall Survival11.1 months
Secondary

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)

ArmMeasureValue (NUMBER)
Docetaxel, Oxaliplatin & BevacizumabResponse Rate by RECIST Criteria42 percentage of responders
Secondary

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

ArmMeasureValue (MEDIAN)
Docetaxel, Oxaliplatin & BevacizumabTime to Treatment Failure4.5 months
Secondary

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

ArmMeasureGroupValue (COUNT_OF_PARTICIPANTS)
Docetaxel, Oxaliplatin & BevacizumabToxicity ProfileNausea4 Participants
Docetaxel, Oxaliplatin & BevacizumabToxicity ProfileVomiting2 Participants
Docetaxel, Oxaliplatin & BevacizumabToxicity ProfileTE Fistula1 Participants
Docetaxel, Oxaliplatin & BevacizumabToxicity ProfileHypertension2 Participants
Docetaxel, Oxaliplatin & BevacizumabToxicity ProfileVenous Thromboemblism1 Participants
Docetaxel, Oxaliplatin & BevacizumabToxicity ProfileNeutropenia13 Participants
Docetaxel, Oxaliplatin & BevacizumabToxicity ProfileLeukopenia1 Participants
Docetaxel, Oxaliplatin & BevacizumabToxicity ProfileGI Perforation3 Participants
Docetaxel, Oxaliplatin & BevacizumabToxicity ProfileNeuropathy5 Participants
Docetaxel, Oxaliplatin & BevacizumabToxicity ProfileDiarrhea3 Participants
Docetaxel, Oxaliplatin & BevacizumabToxicity ProfileDehydration4 Participants
Docetaxel, Oxaliplatin & BevacizumabToxicity ProfileFever2 Participants
Docetaxel, Oxaliplatin & BevacizumabToxicity ProfileFatigue2 Participants
Docetaxel, Oxaliplatin & BevacizumabToxicity ProfileAnorexia2 Participants

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026