Cetuximab With or Without Brivanib in Treating Patients With K-Ras Wild Type Tumours and Metastatic Colorectal Cancer
Colorectal Cancer
About this trial
This is an interventional treatment trial for Colorectal Cancer focused on measuring recurrent colon cancer, stage IV colon cancer, recurrent rectal cancer, stage IV rectal cancer
Eligibility Criteria
DISEASE CHARACTERISTICS:
Histologically confirmed primary colorectal cancer
- Metastatic disease
- Tumor must be confirmed to be K-Ras wild type (i.e., No K-Ras mutation found) by means of mutation analysis performed on representative samples of diagnostic tumor tissue by a central reference laboratory (archival tumor samples are acceptable for K-Ras mutation analysis)
Must have received a prior thymidylate synthase inhibitor (e.g., fluorouracil, capecitabine, raltitrexed, or tegafur-uracil) for adjuvant and/or metastatic disease
- Thymidylate synthase inhibitor may have been given in combination with oxaliplatin or irinotecan hydrochloride
Must meet one of the following criteria:
- Received and failed* an irinotecan hydrochloride-containing regimen (i.e., single-agent or in combination) for treatment of metastatic disease
- Relapsed within 6 months of completion of an irinotecan hydrochloride-containing adjuvant therapy
- Has documented unsuitability** for an irinotecan hydrochloride-containing regimen NOTE: *Failure is defined as either progression of disease or intolerance to the irinotecan-containing regimen, where intolerance is defined as discontinuation due to any of the following: severe allergic reaction or delayed recovery from toxicity preventing retreatment NOTE: **Documented unsuitability for irinotecan includes known hypersensitivity to irinotecan, abnormal glucuronidation of bilirubin, Gilbert's syndrome, previous pelvic/abdominal irradiation, or elderly with comorbid conditions
Must meet one of the following:
- Received and failed* an oxaliplatin-containing regimen (i.e. single-agent or in combination) for treatment of metastatic disease
- Relapsed within 6 months of completion of an oxaliplatin containing adjuvant therapy
- Has documented unsuitability** for an oxaliplatin-containing regimen NOTE: *Failure is defined as either progression of disease or intolerance to the oxaliplatin-containing regimen, where intolerance is defined as discontinuation due to any of the following: severe allergic reaction, persistent severe neurotoxicity or delayed recovery from toxicity preventing retreatment
NOTE: **Documented unsuitability for oxaliplatin includes known hypersensitivity to oxaliplatin or other platinum compounds, pre-existing renal impairment, or Grade 2 or greater neurosensory neuropathy
- Measurable or evaluable disease
- Patient must consent to provision of, and investigator(s) must confirm access to and agree to submit at the request of the NCIC CTG Central Tumor Bank, a representative formalin fixed paraffin block of tumour tissue
- Patient must consent to provision of a sample of blood
No symptomatic CNS metastases
- Patients with signs or symptoms suggestive of brain metastasis are not eligible unless brain metastases are ruled out by CT or MRI scans
PATIENT CHARACTERISTICS:
Inclusion criteria:
- ECOG performance status 0-2
- Absolute granulocyte count ≥ 1.5 x 10^9/L
- Platelet count ≥ 75 x 10^9/L
- Hemoglobin ≥ 80 g/L
- Total bilirubin ≤ 1.5 times upper limit of normal (ULN) (2.0 times ULN with documented liver metastases)
- ALT and AST ≤ 2.5 times ULN (5.0 times ULN with documented liver metastases)
- Serum creatinine ≤ 1.5 times ULN or creatinine clearance > 50 mL/min
- Magnesium > 0.5 mmol/L (1.2 mg/dL)
- LVEF > 45% by ECHO or MUGA scan
- No proteinuria ≥ 2+ on dipstick or ≥ 1 g on 24 hour urine collection
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception prior to, during, and for 12 weeks after completion of study treatment
- Able (i.e., sufficiently fluent) and willing to complete the quality of life (EORTC QLQ-C30 and Skindex-16) and health utilities questionnaires (HUI3) in either English or French
Exclusion criteria:
- A history of other malignancies, except: adequately treated nonmelanoma skin cancer, curatively treated in situ cancer of the cervix, or other solid tumors curatively treated with no evidence of disease for ≥ 5 years
- Any active disease condition which would render the protocol treatment dangerous or impair the ability of the patient to receive protocol therapy
- Any condition (e.g., psychological, geographical, etc.) that does not permit compliance with the protocol
Uncontrolled or significant cardiovascular disease including any of the following:
- Myocardial infarction within 12 months
- Uncontrolled angina within 6 months
- Clinically significant congestive heart failure
- Stroke, transient ischemic attack, or other ischemic event within 12 months
- Severe cardiac valve dysfunction
- Uncontrolled hypertension (consistent elevation of systolic BP > 150 and diastolic BP > 100 mmHg)
History of a thromboembolic event in the last 6 months despite being treated with anticoagulation
- Patients are eligible if they have experienced a thromboembolic event greater than 6 months previously and have initiated and are stable on anticoagulation or if they have previously initiated and are stable on anticoagulation for prevention of thromboembolic events
- Severe restrictive lung disease or radiological pulmonary findings of "interstitial lung disease" on the baseline chest x-ray which, in the opinion of the investigator, represents significant pathology
- Serious non-healing wounds, ulcers, or bone fractures
- History of allergy to brivanib (alaninate or related drug class
- Unable to swallow tablets
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
- Adequately recovered from recent surgery, chemotherapy and/or radiation therapy
- At least 4 weeks must have elapsed from major surgery, prior chemotherapy, prior treatment with an investigational agent or prior radiation therapy
- No prior cetuximab or other therapy* with targets the EGFR pathway (e.g., erlotinib hydrochloride, gefitinib hydrochloride, panitumumab)
- May have received a single prior regimen which targets the VEGFR pathway (e.g., bevacizumab , vatalanib, AZD2171, sorafenib tosylate, sunitinib malate, or others)
- No prior murine monoclonal antibody therapy (e.g., edrecolomab)
- No other concurrent chemotherapy
- No other concurrent therapies targeting the EGFR pathway (e.g., erlotinib, gefitinib, panitumumab, or others) or other therapies targeting the VEGFR pathway (e.g., bevacizumab , vatalanib, AZD2171, sorafenib tosylate, sunitinib malate, or others)
- Concurrent antihypertensive therapies allowed
- Concurrent aspirin allowed
- No other concurrent noncytotoxic experimental agents
Sites / Locations
- Tom Baker Cancer Centre
- Cross Cancer Institute
- BCCA - Abbotsford Centre
- BCCA - Cancer Centre for the Southern Interior
- BCCA - Fraser Valley Cancer Centre
- BCCA - Vancouver Cancer Centre
- CancerCare Manitoba
- The Moncton Hospital
- The Vitalite Health Network - Dr. Leon Richard
- Atlantic Health Sciences Corporation
- Dr. H. Bliss Murphy Cancer Centre
- The Royal Victoria Hospital
- Juravinski Cancer Centre at Hamilton Health Sciences
- Cancer Centre of Southeastern Ontario at Kingston
- Grand River Regional Cancer Centre
- London Regional Cancer Program
- Stronach Regional Health Centre at Southlake
- Lakeridge Health Oshawa
- Ottawa Health Research Institute - General Division
- Algoma District Cancer Program
- Niagara Health System
- Thunder Bay Regional Health Science Centre
- Toronto East General Hospital
- Odette Cancer Centre
- St. Michael's Hospital
- Univ. Health Network-Princess Margaret Hospital
- PEI Cancer Treatment Centre,Queen Elizabeth Hospital
- Hopital Charles LeMoyne
- L'Hotel-Dieu de Levis
- CHUM - Hopital Notre-Dame
- McGill University - Dept. Oncology
- Hopital du Sacre-Coeur de Montreal
- CHUQ-Pavillon Hotel-Dieu de Quebec
- CHA-Hopital Du St-Sacrement
- Centre hospitalier universitaire de Sherbrooke
- Allan Blair Cancer Centre
- Saskatoon Cancer Centre
Arms of the Study
Arm 1
Arm 2
Active Comparator
Active Comparator
Brivanib
Placebo