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

• Sponsor: Barbara Ann Karmanos Cancer Institute (Other)
• Overall Status: Completed
• CT.gov ID: NCT00217581
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 39
• Locations: 4
• Arm: 1
• Actual Duration (Months): 99
• Patients Per Site: 9.8
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Esophageal Cancer; Gastric Cancer	Biological: Bevacizumab; Drug: Docetaxel; Drug: Oxaliplatin	Phase 2

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.

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 Trial of Bevacizumab, Docetaxel, and Oxaliplatin in Gastric and Gastroesophageal Junction Cancer
• Actual Study Start Date: Oct 1, 2004
• Actual Primary Completion Date: Nov 1, 2012
• Actual Study Completion Date: Jan 1, 2013

Arms and Interventions

Arm

Intervention/Treatment

Experimental: 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.

Biological: 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.; Other Names: Avastin ; Drug: Docetaxel; Must be administered 2nd after Bevacizumab and followed by Oxaliplatin.70 mg/m(2), IV over 60 minutes, day 1 of each cycle; Other Names: Taxotere ; Drug: Oxaliplatin; Must be administered 3rd after Bevacizumab and Docetaxel. 75 mg/m(2), IV over 120 minutes, Day 1 of each cycle.; Other Names: Eloxatin

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. Response Rate by RECIST Criteria [After every 2 cycles (1 cycle =21 days)]

   Percentage of Participants with response by RECIST criteria until progression

2. 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.

3. 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

4. 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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 120 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan	United States	48109-0942
2	Barbara Ann Karmanos Cancer Institute	Detroit	Michigan	United States	48201-1379
3	Veterans Affairs Medical Center - Detroit	Detroit	Michigan	United States	48201
4	Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center	Columbus	Ohio	United States	43210-1240

Sponsors and Collaborators

• Barbara Ann Karmanos Cancer Institute
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Philip A. Philip, MD, PhD, FRCP, Barbara Ann Karmanos Cancer Institute
• Principal Investigator: Basil El-Rayes, MD, Barbara Ann Karmanos Cancer Institute

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Clinical trial summary from the National Cancer Institute's PDQ® database

Publications

None provided.

• Responsible Party: Philip Philip, Principal Investigator, Barbara Ann Karmanos Cancer Institute
• ClinicalTrials.gov Identifier: NCT00217581
• Other Study ID Numbers: CDR0000441641; P30CA022453; WSU-D-2840; UMCC-2005-052; AVENTIS-WSU-D-2840
• First Posted: Sep 22, 2005
• Last Update Posted: Mar 26, 2019
• Last Verified: Mar 1, 2019

• Keywords provided by Philip Philip, Principal Investigator, Barbara Ann Karmanos Cancer Institute: 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
• Additional relevant MeSH terms: Stomach Neoplasms; Esophageal Neoplasms; Bevacizumab; Docetaxel; Oxaliplatin

Study Results

Participant Flow

Arm/Group Title	Docetaxel, Oxaliplatin & Bevacizumab
Arm/Group Description	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.
Period Title: Overall Study
STARTED	39
COMPLETED	38
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	Docetaxel, Oxaliplatin & Bevacizumab
Arm/Group Description	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.
Overall Participants	39
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	28 71.8%
>=65 years	11 28.2%
Sex: Female, Male (Count of Participants)
Female	10 25.6%
Male	29 74.4%
Region of Enrollment (Count of Participants)
United States	39 100%

Outcome Measures

1. Primary Outcome

Title	Time to Progression
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Docetaxel, Oxaliplatin & Bevacizumab
Arm/Group Description	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.
Measure Participants	38
Median (95% Confidence Interval) [months]	6.6

2. Secondary Outcome

Title	Response Rate by RECIST Criteria
Description	Percentage of Participants with response by RECIST criteria until progression
Time Frame	After every 2 cycles (1 cycle =21 days)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Docetaxel, Oxaliplatin & Bevacizumab
Arm/Group Description	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. If the 60 min infusion is well tolerated, all subsequent infusions may be delivered over 30 min + or - 10 mins. Docetaxel: Must be administered 2nd after Bevacizumab and followed by Oxaliplatin.70 mg/m(2), IV over 60 minutes, day 1 of each cycle;
Measure Participants	38
Number (95% Confidence Interval) [percentage of responders]	42

3. Secondary Outcome

Title	Toxicity Profile
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Docetaxel, Oxaliplatin & Bevacizumab
Arm/Group Description	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. If the 60 min infusion is well tolerated, all subsequent infusions may be delivered over 30 min + or - 10 mins. Docetaxel: Must be administered 2nd after Bevacizumab and followed by Oxaliplatin.70 mg/m(2), IV over 60 minutes, day 1 of each cycle;
Measure Participants	38
Neutropenia	13 33.3%
Leukopenia	1 2.6%
GI Perforation	3 7.7%
TE Fistula	1 2.6%
Hypertension	2 5.1%
Venous Thromboemblism	1 2.6%
Neuropathy	5 12.8%
Nausea	4 10.3%
Vomiting	2 5.1%
Diarrhea	3 7.7%
Dehydration	4 10.3%
Fever	2 5.1%
Fatigue	2 5.1%
Anorexia	2 5.1%

4. Secondary Outcome

Title	Time to Treatment Failure
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Docetaxel, Oxaliplatin & Bevacizumab
Arm/Group Description	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. If the 60 min infusion is well tolerated, all subsequent infusions may be delivered over 30 min + or - 10 mins. Docetaxel: Must be administered 2nd after Bevacizumab and followed by Oxaliplatin.70 mg/m(2), IV over 60 minutes, day 1 of each cycle;
Measure Participants	38
Median (95% Confidence Interval) [months]	4.5

5. Secondary Outcome

Title	Overall Survival
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Docetaxel, Oxaliplatin & Bevacizumab
Arm/Group Description	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. If the 60 min infusion is well tolerated, all subsequent infusions may be delivered over 30 min + or - 10 mins. Docetaxel: Must be administered 2nd after Bevacizumab and followed by Oxaliplatin.70 mg/m(2), IV over 60 minutes, day 1 of each cycle;
Measure Participants	38
Median (95% Confidence Interval) [months]	11.1

Adverse Events

Arm/Group Title	Docetaxel, Oxaliplatin & Bevacizumab
Arm/Group Description	Administered 1st before Docetaxel & Oxaliplatin.7.5 mg/kg, IV, day 1 of each cycle; 1st cycle, bevacizumab will be delivered over 90 +/- 15 mins. If the 1st IV infusion is tolerated w/o infusion-associated adverse events, the 2nd infusion may be delivered over 60 +/- 10 mins. If the 60 min infusion is well tolerated, all subsequent infusions may be delivered over 30 min +/- 10 mins. Bevacizumab: 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 +/- 15 mins. If the 1st IV infusion is tolerated w/o infusion-associated adverse events, the 2nd infusion may be delivered over 60 +/- 10 mins. If the 60 min infusion is well tolerated, all subsequent infusions may be delivered over 30 min +/- 10 mins. Docetaxel: Must be administered 2nd after Bevacizumab then Oxaliplatin.70 mg/m(2), IV over 60 minutes, day 1 of each cycle;
All Cause Mortality
	Docetaxel, Oxaliplatin & Bevacizumab
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Docetaxel, Oxaliplatin & Bevacizumab
	Affected / at Risk (%)	# Events
Total	23/39 (59%)
Gastrointestinal disorders
Nausea	4/39 (10.3%)	4
Late Dehydration	3/39 (7.7%)	3
Gastrointestinal (GI) Perforation (not graded)	2/39 (5.1%)	2
Vomiting	2/39 (5.1%)	2
General disorders
Fatigue	2/39 (5.1%)	2
Fever	2/39 (5.1%)	2
Investigations
Neutrophils	13/39 (33.3%)	13
White Blood Count (WBC)	1/39 (2.6%)	1
Metabolism and nutrition disorders
Dehydration	4/39 (10.3%)	4
Nervous system disorders
Acute Neuropathy	2/39 (5.1%)	2
Renal and urinary disorders
Proteinuria	1/39 (2.6%)	1
Vascular disorders
Hypertension	2/39 (5.1%)	2
Other (Not Including Serious) Adverse Events
	Docetaxel, Oxaliplatin & Bevacizumab
	Affected / at Risk (%)	# Events
Total	23/39 (59%)
Gastrointestinal disorders
Nausea	10/39 (25.6%)	10
Late Diarrhea	12/39 (30.8%)	12
Vomiting	4/39 (10.3%)	4
General disorders
Fatigue	14/39 (35.9%)	14
Investigations
WBC	2/39 (5.1%)	2
Hemoglobin (HGB)	3/39 (7.7%)	3
Nervous system disorders
Acute Neuropathy	9/39 (23.1%)	9
Chronic Neuropathy	5/39 (12.8%)	5
Vascular disorders
Hypertension	5/39 (12.8%)	5

Limitations/Caveats

The trial completed its planned accrual. There were no significant limitations.

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.