| City: |
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La Crosse |
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State:
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WI |
| Zip Code: |
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54601 |
| Conditions: |
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Colorectal Cancer |
| Purpose: |
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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.
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| Study summary: |
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OBJECTIVES:
Primary
- Compare overall survival of patients with previously untreated metastatic colorectal
cancer treated with cetuximab and/or bevacizumab in combination with either
oxaliplatin, fluorouracil, and leucovorin calcium (FOLFOX) OR irinotecan hydrochloride,
fluorouracil, and leucovorin calcium (FOLFIRI). (Arm III [cetuximab and bevacizumab in
combination with FOLFOX or FOLFIRI] closed to accrual as of 09/10/2009)
Secondary
- Compare response, progression-free survival, time to treatment failure, and duration of
response in patients with unresectable disease treated with these regimens.
- Compare toxicity and 60-day survival of patients with unresectable disease treated with
these regimens.
- Determine whether patients with unresectable disease become eligible for surgical
resection after treatment with these regimens.
OUTLINE: This is a randomized, open-label, multicenter study. Patients are stratified
according to physician-selected chemotherapy (oxaliplatin, leucovorin calcium, and
fluorouracil [FOLFOX] vs irinotecan hydrochloride, leucovorin calcium, or fluorouracil
[FOLFIRI]), prior adjuvant chemotherapy (yes vs no), and prior pelvic radiotherapy (yes vs
no). Patients are randomized to 1 of 3 treatment arms. (Arm III closed to accrual as of
09/10/2009)
- Arm I: Patients receive oxaliplatin IV over 2 hours or irinotecan hydrochloride IV over
30-90 minutes; leucovorin calcium IV over 2 hours; fluorouracil IV continuously over
46-48 hours; and bevacizumab IV over 30-90 minutes on days 1, 15, 29, and 43.
- Arm II: Patients receive oxaliplatin or irinotecan hydrochloride, leucovorin calcium,
and fluorouracil as in arm I. Patients also receive cetuximab IV over 1-2 hours on days
1, 8, 15, 22, 29, 36, 43, and 50.
- Arm III (closed to accrual as of 09/10/2009): Patients receive oxaliplatin or
irinotecan hydrochloride, leucovorin calcium, fluorouracil, and bevacizumab as in arm
I. Patients also receive cetuximab as in arm II.
In all arms, treatment repeats every 56 days for at least 2 courses in the absence of
disease progression, unacceptable toxicity, or planned surgery with curative intent.
For patients whom elective surgery is contemplated, bevacizumab must be discontinued for at
least 8 weeks before surgery and may not be resumed for at least 4 weeks after surgery.
Patients who undergo complete resection of metastatic disease are removed from study.
After completion of study treatment, patients are followed up every 2 months for 5 years and
then every 6 months for 5 years.
PROJECTED ACCRUAL: A total of 2,900 patients will be accrued for this study. |
| Criteria: |
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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 |
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| Study is available at: |
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Gundersen Lutheran Center for Cancer and Blood
La Crosse, WI 54601
United States
Primary Contact:
Clinical Trials Office - Gundersen Lutheran Cancer Center
Email: cancerctr@gundluth.org
Phone: 608-775-2385 |
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If you are interested in this clinical trial please use the contact information above. If you would like to get additional information about this clinical trial please visit ClinicalTrials.gov.
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| Data Source: |
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ClinicalTrials.gov |
| Date Processed: |
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March 21, 2011 |
Modifications to
this listing: |
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Only selected fields are shown, please use the link
above to view all information about this clinical trial. |
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