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A Phase III Trial of Irinotecan / 5-FU / Leucovorin or Oxaliplatin / 5-FU/ Leucovorin With Bevacizumab, or Cetuximab (C225), or With the Combination of Bevacizumab and Cetuximab for Patients With Untr

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Trial Conditions
  • Colorectal Cancer
What is the purpose of this trial?

RATIONALE: Monoclonal antibodies, such as cetuximab and 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. Cetuximab may also stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Bevacizumab may also stop the growth of tumor cells by blocking blood flow to the tumor. Drugs used in chemotherapy, such as fluorouracil, leucovorin, oxaliplatin, and irinotecan, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving monoclonal antibodies together with combination chemotherapy may kill more tumor cells. It is not yet known whether combination chemotherapy is more effective with cetuximab and/or bevacizumab in treating patients with colorectal cancer. PURPOSE: This randomized phase III trial is studying cetuximab and/or bevacizumab when given together with combination chemotherapy to compare how well they work in treating patients with metastatic colorectal cancer.

Date & Status

Active, not recruiting

Who can Participate?

Eligibility

Ages:
18 and older

Gender:
Both

Eligibility

DISEASE CHARACTERISTICS:

- Histologically or cytologically confirmed adenocarcinoma of the colon or rectum

- Locally advanced (unresectable) or metastatic disease

- Patients with resected primary tumors who have documented metastases are
eligible

- Separate histological or cytological confirmation is not required from
patients with a history of colorectal cancer (previously treated by
surgical resection) who have now developed radiological or clinical
evidence of metastatic disease, unless 1 of the following is true:

- An interval of > 5 years has elapsed between the primary surgery and
the development of metastatic disease

- The primary cancer was stage I

- Patient must have a wildtype K-ras gene determined by the SWOG Solid Tumor Repository
laboratory or by local CLIA-certified laboratory

- Patients with a mutation in the K-ras gene not allowed

- The intent of this treatment must be indicated as follows:

- Palliative or neoadjuvant treatment with the potential for resection of all
sites of metastatic disease

- At least 1 paraffin block of previously resected primary tumor or tumor deposit
available

- Patients must have a wildtype K-ras gene

- No known CNS metastases or carcinomatous meningitis

PATIENT CHARACTERISTICS:

Performance status

- ECOG 0-1

Life expectancy

- Not specified

Hematopoietic

- Granulocyte count ≥ 1,500/mm^3

- Platelet count ≥ 100,000/mm^3

- Hemoglobin ≥ 9.0 g/dL (transfusion allowed)

- No history of significant bleeding episodes (e.g., hemoptysis or upper or lower
gastrointestinal bleeding) within the past 6 months unless the source of bleeding has
been resected

Hepatic

- Bilirubin ≤ 1.5 mg/dL

- Albumin ≥ 2.5 g/dL

- No evidence of Gilbert's syndrome for patients assigned to receive FOLFIRI
chemotherapy

- Gilbert's syndrome allowed for patients assigned to receive FOLFOX chemotherapy

Renal

- Creatinine ≤ 1.5 times upper limit of normal

- Protein < 1+ by urinalysis

- Protein < 1 g by 24-hour urine collection for patients with protein ≥ 2+ by
urinalysis

Cardiovascular

- No arterial thromboembolic events within the past 6 months, including any of the
following:

- Myocardial infarction

- Transient ischemic attack

- Cerebrovascular accident

- Unstable angina or angina requiring surgical or medical intervention

- No uncontrolled hypertension (i.e., blood pressure ≥ 160/90 on a regimen of
antihypertensive therapy)

- No New York Heart Association class II-IV congestive heart failure

- No clinically significant peripheral artery disease (i.e., claudication on less than
1 block)

Pulmonary

- No interstitial pneumonia

- No extensive or symptomatic interstitial fibrosis of the lung

- No pleural effusion or ascites that causes ≥ grade 2 dyspnea

Gastrointestinal

- No gastrointestinal perforation within past year

- No uncontrolled, predisposing colonic or small bowel disorder (i.e., > 3 watery or
soft stools daily for patients without a colostomy or ileostomy)

- Patients with a colostomy or ileostomy are eligible at the discretion of the
investigator

Neurologic

- No sensory peripheral neuropathy ≥ grade 2 for patients assigned to receive FOLFOX
chemotherapy

- No uncontrolled seizure disorder

- No active neurological disease

Other

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception during and for at least 2-6 months
after completion of study treatment

- No serious nonhealing wound, ulcer, or bone fracture

- No known hypersensitivity to Chinese hamster ovary cell products or recombinant human
or murine antibodies

- No other malignancy within the past 5 years except adequately treated basal cell or
squamous cell skin cancer or carcinoma in situ of the cervix

PRIOR CONCURRENT THERAPY:

Biologic therapy

- No prior agents that target vascular endothelial growth factor (VEGF) or EGF
receptors including protein products, monoclonal antibodies, or antisense therapies

- No prior bevacizumab or cetuximab

- No concurrent prophylactic filgrastim (G-CSF), pegfilgrastim, or sargramostim
(GM-CSF)

Chemotherapy

- See Radiotherapy

- More than 12 months since prior adjuvant chemotherapy (≤ 6 months in duration) that
included fluorouracil alone or in combination with oxaliplatin or irinotecan
hydrochloride

- No prior regional chemotherapy (e.g., hepatic arterial infusion)

- No other concurrent chemotherapy

Endocrine therapy

- No concurrent hormonal therapy except steroids for adrenal failure, hormones for
noncancer-related conditions (e.g., insulin for diabetes), or intermittent
dexamethasone as an antiemetic

Radiotherapy

- Prior radiotherapy with radiosensitizing chemotherapy allowed

- Prior standard adjuvant chemoradiotherapy for rectal cancer allowed

- At least 4 weeks since prior radiotherapy

- No prior radiotherapy to > 25% of bone marrow

- No concurrent palliative radiotherapy except whole brain irradiation for documented
CNS disease

Surgery

- See Disease Characteristics

- At least 4 weeks since prior major surgery

- At least 2 weeks since prior minor surgery

- Insertion of a vascular access device is not considered a prior surgery

- Recovered from all prior surgery

Other

- At least 4 weeks since prior itraconazole or ketoconazole

- No prior tyrosine kinase inhibitor therapy

- No prior systemic treatment for advanced or metastatic colorectal cancer

- No concurrent aprepitant

- Concurrent full-dose anticoagulation (i.e., warfarin) allowed provided all of the
following criteria are met:

- In-range INR (usually 2-3) on a stable dose of oral anticoagulant or stable dose
of low molecular weight heparin

- No active bleeding

- No pathological condition with a high risk of bleeding (e.g., tumor involving
major vessels or known varices)

- Concurrent antiplatelet agents allowed

- Concurrent daily prophylactic aspirin or anticoagulation for atrial fibrillation
allowed

Gender: Both
Steward Physician(s)
  • Alan P. Venook, MD
  • Charles D. Blanke, MD, FACP
Facilities
  • St. Elizabeth's Medical Center - Active, not recruiting
  • Norwood Hospital - Active, not recruiting
Trial Interventions
Biological
  • bevacizumab
  • cetuximab
Drug
  • fluorouracil
  • irinotecan hydrochloride
  • leucovorin calcium
  • oxaliplatin
Physician Researcher

Investigator Name:

  • Alan P. Venook, MD
  • Charles D. Blanke, MD, FACP

Other Information

Sponsor: Cancer and Leukemia Group B
Phase: Phase 3
Trial ID: NCT00265850
Volunteers:  Not Accepting Healthy Volunteers

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