Combination Chemotherapy Plus Bevacizumab With or Without Oxaliplatin in Treating Older Patients With Metastatic Colorectal Cancer
- Conditions
- Cognitive/Functional EffectsColorectal CancerNeurotoxicity
- Interventions
- Biological: bevacizumab
- Registration Number
- NCT01279681
- Lead Sponsor
- Alliance for Clinical Trials in Oncology
- Brief Summary
This randomized phase III trial studies how well combination chemotherapy plus bevacizumab with or without oxaliplatin works in treating older patients with colorectal cancer that has spread to other places in the body. Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells. Monoclonal antibodies, such as bevacizumab, may block tumor growth in different ways by targeting certain cells. Bevacizumab may also stop the growth of cancer by blocking blood flow to the tumor. It is not yet known whether combination chemotherapy plus bevacizumab is more effective with or without oxaliplatin in treating colorectal cancer.
- Detailed Description
PRIMARY OBJECTIVES:
I. To compare the progression-free survival (PFS) of elderly patients with metastatic colorectal carcinoma who are randomized to receive fluoropyrimidine (fluorouracil)-based therapy plus bevacizumab, with or without oxaliplatin.
SECONDARY OBJECTIVES:
I. In a prospectively planned pooled analysis with a similar trial to be conducted by the Japanese Clinical Oncology Group (JCOG), evaluate and compare the overall survival (OS) of elderly patients with metastatic colorectal carcinoma who are randomized to receive fluoropyrimidine-based therapy plus bevacizumab, with or without oxaliplatin.
II. To assess and compare response rates and adverse events of elderly patients with metastatic colorectal carcinoma randomized to receive fluoropyrimidine-based therapy plus bevacizumab, with or without oxaliplatin.
OUTLINE: Patients are randomized to 1 of 2 treatment arms and assigned to treatment groups based on physician decision for fluoropyrimidine.
ARM A: Patients receive either 5FU/LV or Capecitabine, plus BEV. 5FU/LV + BEV is comprised of 5FU IV over 46-48 hours, LV calcium IV over 2 hours, and BEV IV over 10-90 minutes on day 1. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity. Capecitabine + BEV is comprised of capecitabine PO BID on days 1-14 and BEV IV over 30-90 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
ARM B: Patients receive either mFOLFOX7 plus BEV, or Capecitabine + OXAL (XELOX) plus BEV. mFOLFOX7 + BEV is comprised of OXAL IV over 2 hours, LV calcium IV over 2 hours, and 5FU IV over 46-48 hours on day 1. Patients also receive BEV IV over 10-90 minutes on day 1. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity. XELOX + BEV is comprised of OXAL IV over 2 hours on day 1 and capecitabine PO BID on days 1-14. Patients also receive BEV IV over 30-90 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up periodically for 5 years.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 32
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm A [fluoropyrimidine + bevacizumab (BEV)] bevacizumab Patients receive either 5FU/LV or Capecitabine, plus BEV. 5FU/LV + BEV is comprised of 5FU IV over 46-48 hours, LV calcium IV over 2 hours, and BEV IV over 10-90 minutes on day 1. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity. Capecitabine + BEV is comprised of capecitabine PO BID on days 1-14 and BEV IV over 30-90 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Arm B [fluoropyrimidine/oxaliplatin (OXAL) + BEV] bevacizumab Patients receive either mFOLFOX7 plus BEV, or Capecitabine + OXAL (XELOX) plus BEV. mFOLFOX7 + BEV is comprised of OXAL IV over 2 hours, LV calcium IV over 2 hours, and 5FU IV over 46-48 hours on day 1. Patients also receive BEV IV over 10-90 minutes on day 1. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity. XELOX + BEV is comprised of OXAL IV over 2 hours on day 1 and capecitabine PO BID on days 1-14. Patients also receive BEV IV over 30-90 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Arm A [fluoropyrimidine + bevacizumab (BEV)] leucovorin calcium Patients receive either 5FU/LV or Capecitabine, plus BEV. 5FU/LV + BEV is comprised of 5FU IV over 46-48 hours, LV calcium IV over 2 hours, and BEV IV over 10-90 minutes on day 1. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity. Capecitabine + BEV is comprised of capecitabine PO BID on days 1-14 and BEV IV over 30-90 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Arm B [fluoropyrimidine/oxaliplatin (OXAL) + BEV] leucovorin calcium Patients receive either mFOLFOX7 plus BEV, or Capecitabine + OXAL (XELOX) plus BEV. mFOLFOX7 + BEV is comprised of OXAL IV over 2 hours, LV calcium IV over 2 hours, and 5FU IV over 46-48 hours on day 1. Patients also receive BEV IV over 10-90 minutes on day 1. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity. XELOX + BEV is comprised of OXAL IV over 2 hours on day 1 and capecitabine PO BID on days 1-14. Patients also receive BEV IV over 30-90 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Arm A [fluoropyrimidine + bevacizumab (BEV)] capecitabine Patients receive either 5FU/LV or Capecitabine, plus BEV. 5FU/LV + BEV is comprised of 5FU IV over 46-48 hours, LV calcium IV over 2 hours, and BEV IV over 10-90 minutes on day 1. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity. Capecitabine + BEV is comprised of capecitabine PO BID on days 1-14 and BEV IV over 30-90 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Arm A [fluoropyrimidine + bevacizumab (BEV)] fluorouracil Patients receive either 5FU/LV or Capecitabine, plus BEV. 5FU/LV + BEV is comprised of 5FU IV over 46-48 hours, LV calcium IV over 2 hours, and BEV IV over 10-90 minutes on day 1. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity. Capecitabine + BEV is comprised of capecitabine PO BID on days 1-14 and BEV IV over 30-90 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Arm B [fluoropyrimidine/oxaliplatin (OXAL) + BEV] capecitabine Patients receive either mFOLFOX7 plus BEV, or Capecitabine + OXAL (XELOX) plus BEV. mFOLFOX7 + BEV is comprised of OXAL IV over 2 hours, LV calcium IV over 2 hours, and 5FU IV over 46-48 hours on day 1. Patients also receive BEV IV over 10-90 minutes on day 1. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity. XELOX + BEV is comprised of OXAL IV over 2 hours on day 1 and capecitabine PO BID on days 1-14. Patients also receive BEV IV over 30-90 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Arm B [fluoropyrimidine/oxaliplatin (OXAL) + BEV] fluorouracil Patients receive either mFOLFOX7 plus BEV, or Capecitabine + OXAL (XELOX) plus BEV. mFOLFOX7 + BEV is comprised of OXAL IV over 2 hours, LV calcium IV over 2 hours, and 5FU IV over 46-48 hours on day 1. Patients also receive BEV IV over 10-90 minutes on day 1. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity. XELOX + BEV is comprised of OXAL IV over 2 hours on day 1 and capecitabine PO BID on days 1-14. Patients also receive BEV IV over 30-90 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Arm B [fluoropyrimidine/oxaliplatin (OXAL) + BEV] oxaliplatin Patients receive either mFOLFOX7 plus BEV, or Capecitabine + OXAL (XELOX) plus BEV. mFOLFOX7 + BEV is comprised of OXAL IV over 2 hours, LV calcium IV over 2 hours, and 5FU IV over 46-48 hours on day 1. Patients also receive BEV IV over 10-90 minutes on day 1. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity. XELOX + BEV is comprised of OXAL IV over 2 hours on day 1 and capecitabine PO BID on days 1-14. Patients also receive BEV IV over 30-90 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
- Primary Outcome Measures
Name Time Method Progression-Free Survival Up to 5 years Progression was defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), 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. Progression free survival was defined as the time (in months) from the date of randomization to the date of documented disease progression or death, whichever occurs first. Patients were followed until progression (and progression was declared) regardless of whether the patient was on the first line treatment or not. Patients who progress following a missed scan will have their date of progression back-dated to the date of missing scan. Patients without a progression who are still alive at the time of analysis will be censored at the date of last follow-up.
- Secondary Outcome Measures
Name Time Method Overall Survival Up to 5 years Overall survival was defined as the time (in months) from randomization to death.
Number of Participants With Grade 3 Adverse Events At Least Possibly Related to Treatment Up to 42 days after treatment discontinuation Adverse events were assessed using the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0
Response Rate, Defined as the Percentage of Patients in Each Arm Who Have an Objective Status of Complete Response or Partial Response, Confirmed by a Second Assessment Measured at Least 6 Weeks From the Initial Assessment Up to 5 years Response was defined using Response Evaluation Criteria In Solid Tumors (RECIST) criteria:
* Complete Response (CR): disappearance of all target lesions;
* Partial Response (PR) 30% decrease in sum of longest diameter of target lesions;
* Progressive Disease (PD): 20% increase in sum of longest diameter of target lesions;
* Stable Disease (SD): small changes that do not meet above criteria.
Response rate is reported as the percentage of participants who achieved Complete Response or Partial Response.