Clinical trial NCT00640471 (phase 3, status: completed)
Conditions: colorectal cancer
ICD codes: C05.2, C10.0, C16.0, C16.4, C17.0, C17.1, C17.2
Drugs: brivanib alaninate
SMILES: C[C@H](COC1=CN2N=CN=C(OC3=CC=C4NC(C)=CC4=C3F)C2=C1C)OC(=O)[C@H](C)N
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