Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Combination Chemotherapy and Bevacizumab in Treating Patients With Stage IV Colon Cancer That Cannot Be Removed By Surgery

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00321828
Recruitment Status : Completed
First Posted : May 4, 2006
Results First Posted : January 14, 2013
Last Update Posted : January 24, 2013
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
NSABP Foundation Inc

Tracking Information
First Submitted Date  ICMJE May 2, 2006
First Posted Date  ICMJE May 4, 2006
Results First Submitted Date  ICMJE October 31, 2012
Results First Posted Date  ICMJE January 14, 2013
Last Update Posted Date January 24, 2013
Study Start Date  ICMJE March 2006
Actual Primary Completion Date November 2009   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 8, 2013)
Major Morbidity Related to the Intact Primary Tumor [ Time Frame: 24 months ]
Cumulative incidence was used to compute percent probability of morbidity. Cumulative incidence at time t measures the probability of a participant having an event (i.e., Colonic bleeding, perforation, bowel obstruction, or fistula formation requiring surgery or resulting in patient death) over the given duration, t. It involves computing the probability of an event at any observed time (i.e., the number of new cases during a period divided by the number of subjects at risk) and multiplying these successive probabilities by any early computed probability to get the final estimate.
Original Primary Outcome Measures  ICMJE Not Provided
Change History Complete list of historical versions of study NCT00321828 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: January 4, 2010)
  • Local Complications as Assessed by Colonic Obstruction Requiring Hospitalization (But Not Surgery) for Medical Management, Stent Placement, Laser Treatment, or Fulguration [ Time Frame: Time from start of study through year 5 ]
  • Local Complications as Assessed by Gastrointestinal Bleeding Requiring Transfusion But Not Requiring Surgery [ Time Frame: Time from start of study through year 5 ]
  • Local Complications as Assessed by Fistula Formation (Self-draining Enterocutaneous Fistula and Intra-abdominal Abscess Requiring Percutaneous Drainage) Not Requiring Surgery [ Time Frame: Time from start of study through year 5 ]
  • Local Complications as Assessed by Other Events Related to the Intact Primary Tumor Which Require Hospitalization But Not Surgery [ Time Frame: Time from start of study through year 5 ]
  • Serious Adverse Events (Grades 3, 4, and 5) as Defined by CTCAE v3.0 [ Time Frame: Time from start of study through year 5 ]
  • Overall Survival as Measured by Death From Any Cause [ Time Frame: Time from start of study through year 5 ]
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Combination Chemotherapy and Bevacizumab in Treating Patients With Stage IV Colon Cancer That Cannot Be Removed By Surgery
Official Title  ICMJE A Phase II Trial of 5-Fluorouracil, Leucovorin, and Oxaliplatin (mFOLFOX6) Chemotherapy Plus Bevacizumab for Patients With Unresectable Stage IV Colon Cancer and a Synchronous Asymptomatic Primary Tumor
Brief Summary

RATIONALE: Drugs used in chemotherapy, such as fluorouracil, leucovorin, and oxaliplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. 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 help kill them or carry tumor-killing substances to them. Bevacizumab may also stop the growth of colon cancer by blocking blood flow to the tumor. Giving combination chemotherapy together with bevacizumab may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving combination chemotherapy together with bevacizumab works in treating patients with stage IV colon cancer that cannot be removed by surgery.

Detailed Description

OBJECTIVES:

Primary

  • Determine the rate of major morbidity in patients with unresectable stage IV colon cancer and a synchronous asymptomatic primary tumor treated with fluorouracil, leucovorin calcium, and oxaliplatin (mFOLFOX6) in combination with bevacizumab without resection of the primary tumor.

Secondary

  • Determine the rate of specific events related to the intact primary tumor requiring hospitalization or a major intervention but not requiring surgery.
  • Determine the rate of ≥ grade 3 toxicity as defined by the Common Terminology Criteria for Adverse Events version 3.0 (CTCAE v3.0) that is related to study therapy prior to disease progression.
  • Determine overall survival of patients treated with this regimen.

OUTLINE: This is a multicenter study.

Patients receive bevacizumab IV over 30-90 minutes, oxaliplatin IV given concurrently with leucovorin calcium IV over 2 hours on day 1 and fluorouracil IV continuously over 46 hours on days 1 and 2. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed periodically for 5 years after study entry.

PROJECTED ACCRUAL: A total of 90 patients will be accrued for this study.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Colorectal Cancer
Intervention  ICMJE
  • Biological: bevacizumab
    bevacizumab 5 mg/kg IV on day 1 every 14 days until excessive toxicity or disease progression
  • Drug: fluorouracil
    5-FU 400 mg/m2 IV bolus over 2-4 minutes then 2400 mg/m2 IV continuous infusion over 46 hours on day 1 every 14 days until excessive toxicity or disease progression
    Other Name: 5-FU
  • Drug: leucovorin
    leucovorin 400 mg/m2 IV on day 1 every 14 days until excessive toxicity or disease progression
    Other Name: leucovorin calcium
  • Drug: oxaliplatin
    Oxaliplatin 85 mg/m2 IV on day 1 every 14 days until excessive toxicity or disease progression
Study Arms  ICMJE Experimental: Arm 1: Oxaliplatin + Leucovorin + 5-Fluorouracil + Bevacizumab
Oxaliplatin + Leucovorin + 5-Fluorouracil + Bevacizumab
Interventions:
  • Biological: bevacizumab
  • Drug: fluorouracil
  • Drug: leucovorin
  • Drug: oxaliplatin
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: November 9, 2006)
90
Original Enrollment  ICMJE Not Provided
Actual Study Completion Date  ICMJE December 2012
Actual Primary Completion Date November 2009   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

DISEASE CHARACTERISTICS:

  • Histologically or cytologically confirmed adenocarcinoma of the colon

    • No histological findings other than adenocarcinoma of the colon
    • If the primary colon tumor and the metastatic lesions have been identified at the same time and it is not possible to biopsy the colonic lesion, the patient will be eligible without histologic confirmation of the primary cancer of the colon as long as other radiographic studies or scans document the characteristics of a colon cancer AND the biopsy of a metastatic site confirms diagnosis of adenocarcinoma suggestive of a primary tumor of the colon
  • Unresected primary tumor of the colon AND radiographically confirmed metastatic colon cancer (single or multiple sites of metastases) that are not considered surgically resectable for cure by chest imaging and CT scan or MRI of the abdomen within the past 4 weeks and by endoscopy within the past 8 weeks
  • Asymptomatic primary tumor

    • No obstruction, perforation, or active bleeding requiring transfusion
  • Distal extent of the tumor must be ≥ 12 cm from the anal verge on endoscopy
  • Not a candidate for curative surgical resection of all metastatic and colon primary tumors
  • No evidence of Central Nervous System (CNS) metastases
  • No recurrent local or metastatic disease after prior adjuvant therapy
  • No diagnosis of rectal carcinoma

PATIENT CHARACTERISTICS:

  • Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
  • Absolute neutrophil count ≥ 1200/mm³
  • Platelet count ≥ 100,000/mm³
  • Hemoglobin ≥ 9 g/dL
  • Aspartate aminotransferase (AST) ≤ 2.5 times upper limit of normal (ULN) (≤ 5.0 times ULN if liver metastases are present)
  • Alkaline phosphatase ≤ 3.0 times ULN (≤ 5.0 times ULN if liver metastases are present)
  • Bilirubin ≤ 1.5 times ULN (≤ 2.0 times ULN if liver metastases are present)
  • Creatinine < 1.8 mg/dL
  • Urine dipstick indicating 0-1+ protein

    • If dipstick reading is ≥ 2+, a 24-hour urine collection must demonstrate < 1 g of protein
  • Prothrombin Time and International Normalized Ratio (PT/INR) ≤ 1.5 unless the patient is on therapeutic doses of warfarin, in which case the following criteria must be met:

    • Patient must have an in-range INR (between 2 and 3) on a stable dose of warfarin
    • Patient must not have active bleeding or a pathologic condition that is associated with a high risk of bleeding
  • Patients with a history of non-colorectal malignancies must be disease free for ≥ 5 years prior to study entry and be deemed at low risk for recurrence
  • Patients with the following cancers are eligible if diagnosed and treated within the past 5 years:

    • Carcinoma in situ of the colon
    • Melanoma in situ
    • Basal cell or squamous cell carcinoma of the skin
    • Carcinoma in situ of the cervix
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for 3 months after the completion of study therapy
  • No uncontrolled blood pressure (BP), defined as BP > 150/100 mm Hg
  • No nonmalignant systemic disease that would preclude any of the study therapy drugs, compromise the safety of the patient, or inhibit the patient's ability to participate in the study, including any of the following:

    • New York Heart Association class III or IV cardiac disease
    • Myocardial infarction within the past 6 months
    • Unstable angina within the past 6 months
    • Symptomatic arrhythmia
  • No transient ischemic attack or cerebrovascular accident within the past 6 months
  • No symptomatic peripheral vascular ischemia within the past 6 months
  • No arterial thrombotic event within the past 6 months
  • No gastroduodenal ulcer(s) determined by endoscopy to be active
  • No gastrointestinal perforation within the past 12 months
  • No serious or nonhealing wound, skin ulcer, or bone fracture
  • No significant traumatic injury within the past 28 days
  • No significant episodes of acute bleeding requiring blood transfusion within the past 6 months
  • No clinically significant (≥ grade 2) peripheral neuropathy (neurosensory or neuromotor toxicity)
  • No pulmonary fibrosis or interstitial pneumonitis by chest x-ray
  • No psychiatric or addictive disorders or other conditions that would preclude the patient from meeting study requirements

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • No prior systemic chemotherapy, radiation therapy, or surgery for this malignancy
  • No prior endoscopic management of this malignancy other than biopsy, including endoscopic stent placement, fulguration, or laser treatment
  • More than 30 days since prior investigational drugs
  • More than 28 days since prior major surgical procedure or open biopsy
  • More than 7 days since prior core biopsy or other minor procedure, excluding placement of a vascular access device
  • No concurrent major surgery unrelated to intact primary colon cancer
  • No concurrent radiotherapy
  • No concurrent filgrastim (G-CSF) or pegfilgrastim as primary prophylaxis for neutropenia
  • No concurrent halogenated antiviral agents
  • No other concurrent investigational drugs
  • No other concurrent antineoplastic agents
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00321828
Other Study ID Numbers  ICMJE NSABP C-10
U10CA012027 ( U.S. NIH Grant/Contract )
CDR0000463513 ( Other Identifier: NCI )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party NSABP Foundation Inc
Study Sponsor  ICMJE NSABP Foundation Inc
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Principal Investigator: Norman Wolmark, MD NSABP Foundation Inc
PRS Account NSABP Foundation Inc
Verification Date January 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP