Trial record 1 of 1 for:    NCT01279681
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Combination Chemotherapy Plus Bevacizumab With or Without Oxaliplatin in Treating Older Patients With Metastatic Colorectal Cancer

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified December 2012 by National Cancer Institute (NCI)
Sponsor:
Collaborators:
Cancer and Leukemia Group B
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01279681
First received: January 18, 2011
Last updated: January 2, 2013
Last verified: December 2012
  Purpose

RATIONALE: 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, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. 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.

PURPOSE: This randomized phase III clinical trial is studying how well combination chemotherapy plus bevacizumab with or without oxaliplatin works in treating older patients with metastatic colorectal cancer.


Condition Intervention Phase
Cognitive/Functional Effects
Colorectal Cancer
Neurotoxicity
Biological: bevacizumab
Drug: capecitabine
Drug: fluorouracil
Drug: leucovorin calcium
Drug: oxaliplatin
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Masking: Open Label
Primary Purpose: Treatment
Official Title: Randomized Phase III Trial of mFOLFOX7 or XELOX Plus Bevacizumab Versus 5-Fluorouracil/Leucovorin or Capecitabine Plus Bevacizumab as First-line Treatment in Elderly Patients With Metastatic Colorectal Cancer

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Progression-free survival, defined as the time (in days) from the date of randomization to the date of documented disease progression or death, whichever occurs first [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Overall survival, defined as the time (in days) from randomization to death [ Designated as safety issue: No ]
  • Response rate, defined as the proportion 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 [ Designated as safety issue: No ]
  • Adverse events as per the CTEP Active Version of the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 grading [ Designated as safety issue: Yes ]

Estimated Enrollment: 380
Study Start Date: January 2011
Estimated Primary Completion Date: August 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm A1
Patients receive fluorouracil IV over 46-48 hours, leucovorin calcium IV over 2 hours, and bevacizumab IV over 10-90 minutes on day 1. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.
Biological: bevacizumab
Given IV
Drug: fluorouracil
Given IV
Drug: leucovorin calcium
Given IV
Experimental: Arm A2
Patients receive capecitabine orally (PO) twice daily on days 1-14 and bevacizumab IV over 30-90 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Biological: bevacizumab
Given IV
Drug: capecitabine
Given orally
Active Comparator: Arm B1
Patients receive mFOLFOX7 comprising oxaliplatin IV over 2 hours, leucovorin calcium IV over 2 hours, and fluorouracil IV over 46-48 hours on day 1. Patients also receive bevacizumab IV over 10-90 minutes on day 1. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.
Biological: bevacizumab
Given IV
Drug: fluorouracil
Given IV
Drug: leucovorin calcium
Given IV
Drug: oxaliplatin
Given IV
Experimental: Arm B2
Patients receive XELOX comprising oxaliplatin IV over 2 hours on day 1 and capecitabine PO twice daily on days 1-14. Patients also receive bevacizumab IV over 30-90 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Biological: bevacizumab
Given IV
Drug: capecitabine
Given orally
Drug: oxaliplatin
Given IV

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   70 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Patients must have metastatic colorectal cancer that has been histologically or cytologically confirmed

    • Histologic confirmation can be obtained from the primary tumor with appropriate imaging studies confirming metastatic spread
  • No known central nervous system or brain metastasis that are either symptomatic or untreated

    • If a patient has a resection of the metastasis and is no longer symptomatic, the patient is eligible for the study
    • Patients with neurological symptoms must undergo a CT scan/MRI of the brain to exclude brain metastasis

PATIENT CHARACTERISTICS:

  • Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0, 1, or 2
  • Life expectancy ≥ 3 months
  • Absolute neutrophil count (ANC) ≥ 1,500/mm^3
  • Peripheral platelet count (PLT) ≥ 100,000/mm^3
  • Hemoglobin (HgB) > 9.0 g/dL
  • Total bilirubin ≤ 1.5 x upper limit of normal (ULN)
  • Aspartate transaminase (AST) ≤ 2.5 x ULN (≤ 5 x ULN for patients with liver involvement)
  • Alkaline phosphatase ≤ 3 x ULN (≤ 5 x ULN for patients with liver involvement)
  • Creatinine ≤ 1.5 x ULN
  • No calculated creatinine clearance < 60 mL/minute

    • NOTE: If calculated creatinine clearance does not meet eligibility requirement, a 24-hour urine can be collected for a creatinine clearance, and the patient can be enrolled if measured creatinine clearance ≥ 60 mL/minute.
  • INR < 1.5 x ULN unless patients are receiving anti-coagulation therapy

    • Patients receiving prophylactic anti-coagulation therapy with an agent such as warfarin or heparin are allowed to participate if INR ≤ 3.0
  • UPC ratio < 1 or urine dipstick < 2+

    • NOTE: Urine protein must be screened by urine analysis for urine protein creatinine (UPC) ratio or by dipstick. For UPC ratio ≥ 1.0 or urine dipstick ≥ 2+, 24-hour urine protein must be obtained and the level should be < 1,000 mg.
  • No men of childbearing potential who are unwilling to employ adequate contraception during and for 6 months after the last dose of bevacizumab
  • Ability to complete questionnaire(s) by themselves or with assistance
  • Willing to provide mandatory blood samples for correlative research purposes
  • No co-morbid systemic illnesses or other severe concurrent disease that, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of the safety and adverse events of the prescribed regimens
  • No immunocompromised patients (other than that related to the use of corticosteroids) including patients known to be HIV positive with CD4 < 100 cells/uL
  • No uncontrolled intercurrent illness including, but not limited to:

    • Ongoing or active infection
    • Symptomatic congestive heart failure
    • Unstable angina pectoris
    • Cardiac arrhythmia
    • Psychiatric illness/social situations that would limit compliance with study requirements
  • No other active malignancy ≤ 3 years prior to randomization EXCEPT for nonmelanotic skin cancer or carcinoma-in-situ of the cervix
  • No New York Heart Association (NYHA) classification III or IV congestive heart failure
  • No inadequately controlled hypertension (systolic blood pressure of > 150 mm Hg or diastolic blood pressure > 100 mm Hg on anti-hypertensive medications)
  • No significant traumatic injury ≤ 28 days prior to randomization
  • No active or recent hemoptysis (≥ ½ teaspoon of bright red blood per episode) ≤ 30 days prior to randomization
  • No history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess ≤ 6 months prior to randomization
  • No serious non-healing wound, active ulcer, or untreated bone fracture

    • NOTE: Patients with fractures secondary to metastatic disease are eligible after appropriate radiotherapy.
  • No history of hypertensive crisis or hypertensive encephalopathy
  • No patient that has experienced any arterial thromboembolic events including, but not limited to:

    • Myocardial infarction
    • Stroke
    • Transient ischemic attack (TIA)
    • Cerebrovascular accident
    • Unstable angina ≤ 6 months prior to randomization
    • Congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias
  • No significant vascular disease (e.g., aortic aneurysm, aortic dissection) or recent peripheral arterial thrombosis ≤ 6 months prior to randomization
  • No evidence or history of bleeding diathesis (greater than normal risk of bleeding), coagulopathy (in the absence of therapeutic anticoagulation), or hemorrhage/bleeding event > grade 3 ≤ 4 weeks prior to randomization
  • No known hypersensitivity to any of the components of 5-fluorouracil/leucovorin, capecitabine, oxaliplatin, or bevacizumab
  • No clinically significant peripheral neuropathy at the time of randomization (defined in the NCI Common Terminology Criteria for Adverse Events [CTCAE] v4.0 as ≥ grade 2 neurosensory or neuromotor toxicity)

PRIOR CONCURRENT THERAPY:

  • No prior chemotherapy, radiation therapy, immunotherapy, or biological therapy for recurrent or metastatic colorectal cancer

    • NOTE: Prior chemotherapy or radiotherapy is permitted if they had been administered as adjuvant or neoadjuvant therapy and a complete surgical resection of the original colorectal cancer had been achieved.
  • No progressive disease ≤ 12 months of completing oxaliplatin-containing adjuvant therapy
  • No prior radiation to > 30% of the bone marrow at any time
  • No major surgical procedures or open biopsy ≤ 28 days prior to randomization or anticipation of need for elective or planned major surgical procedure during the course of the study
  • No core biopsy or other minor surgical procedures ≤ 7 days prior to randomization

    • NOTE: Placement of a vascular access device is allowed.
  • If there is a history of prior malignancy, patients must not be receiving other specific treatment (other than hormonal therapy) for this prior cancer
  • Not receiving any other investigational agent which would be considered as a treatment for the primary neoplasm
  • Patients receiving full-dose anticoagulants are eligible provided the patient has been on a stable dose, for at least 2 weeks, of low molecular weight heparin or warfarin and has an INR range 2-3
  • No aspirin doses > 325 mg daily
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01279681

Sponsors and Collaborators
North Central Cancer Treatment Group
Cancer and Leukemia Group B
Investigators
Principal Investigator: Axel Grothey, MD Mayo Clinic
Investigator: Nadine J. McCleary, MD, MPH Dana-Farber Cancer Institute
  More Information

Additional Information:
No publications provided

Responsible Party: Axel Grothey, Mayo Clinic Cancer Center
ClinicalTrials.gov Identifier: NCT01279681     History of Changes
Other Study ID Numbers: CDR0000692257, NCCTG-N0949
Study First Received: January 18, 2011
Last Updated: January 2, 2013
Health Authority: Unspecified

Keywords provided by National Cancer Institute (NCI):
neurotoxicity
cognitive/functional effects
stage IVA colon cancer
stage IVA rectal cancer
stage IVB colon cancer
stage IVB rectal cancer
recurrent colon cancer
recurrent rectal cancer

Additional relevant MeSH terms:
Colorectal Neoplasms
Neurotoxicity Syndromes
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Nervous System Diseases
Poisoning
Chemically-Induced Disorders
Bevacizumab
Capecitabine
Oxaliplatin
Fluorouracil
Leucovorin
Levoleucovorin
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Growth Inhibitors
Antineoplastic Agents
Therapeutic Uses
Antimetabolites, Antineoplastic

ClinicalTrials.gov processed this record on September 18, 2014