Reolysin in Combination With FOLFOX6 and Bevacizumab or FOLFOX6 and Bevacizumab Alone in Metastatic Colorectal Cancer
Condition: Colorectal Cancer
MeSH terms: Colorectal Neoplasms
Intervention: Folfox plus Bevacizumab and reolysin; Folfox plus Bevacizumab
Intervention description: FOLFOX6/bevacizumab given every 14 days plus reolysin days 1-5 on cycles 1, 2, 4, 6, 8 and alternate cycles thereafter; FOLFOX6/bevacizumab given every 14 days.
Intervention MeSH terms: Leucovorin; Bevacizumab; Fluorouracil; Oxaliplatin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 109.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The purpose of this study is to find out if giving reolysin in combination with FOLFOX6/
      bevacizumab can offer better results than standard therapy with FOLFOX6/ bevacizumab.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must have a histological diagnosis of colorectal adenocarcinoma.

          -  All patients must have a formalin fixed paraffin embedded tissue block (from their
             primary or metastatic tumour) available for translational studies and must have
             provided informed consent for the release of the block.

          -  Presence of clinically and/or radiologically documented disease. All radiology studies
             must be performed within 28 days prior to randomization (within 35 days if negative).
             All patients must have measurable disease as defined by RECIST 1.1.

        The criteria for defining measurable disease are as follows:

        Chest X-ray ≥ 20 mm CT/MRI scan (with slice thickness of < 5 mm) ≥ 10 mm longest diameter
        Physical exam (using calipers) ≥ 10 mm Lymph nodes by CT scan ≥ 15 mm measured in short
        axis

          -  Patients must have advanced and or metastatic disease, for which no curative therapy
             exists and for which systemic therapy is indicated.

          -  ECOG performance of 0, 1 or 2.

          -  Age ≥ 18 years of age.

          -  Previous Therapy

        Surgery:

        Previous major surgery is permitted provided that it has been at least 21days prior to
        patient randomization and that wound healing has occurred.

        Chemotherapy:

        Patients may NOT have received any prior cytotoxic chemotherapy for advanced or metastatic
        disease. Prior adjuvant fluoropyrimidine-based therapy is permitted provided completed at
        least one year prior to enrollment and the regimen did not include oxaliplatin or
        bevacizumab. Exceptions may be made for low dose chemotherapy given as a radiosensitizing
        agent.

        Other Therapy:

        Patients may have received other therapies including immunotherapy, or with signal
        transduction inhibitors, providing that the patient has recovered from all reversible drug
        related toxicity (with the exception of alopecia) and adequate washout period has been met.

        Radiation:

        Prior external beam radiation is permitted provided a minimum of 4 weeks has elapsed
        between the last dose and enrollment to the trial. Exceptions may be made for low dose,
        non-myelosuppressive radiotherapy after consultation with NCIC CTG.

          -  Laboratory Requirements (must be done within 7 days prior to randomization)

        Hematology:

        Granulocytes (AGC) ≥ 1.5 x 10^9/L Platelets ≥ 100 x 10^9/L

        Biochemistry:

        Serum creatinine ≤ 1.5 x ULN Total bilirubin ≤ 1.0 x ULN (unless elevated secondary to
        conditions such as Gilbert's disease) ALT and AST ≤ 3 x ULN (Note: ≤ 5 x ULN if documented
        liver metastasis) Proteinuria < 2g/24 hrs (screen using spot testing; if ≥ grade 2 repeat
        with mid-stream urine - if still ≥ grade 2 then urine collection for 24 hours to confirm
        <2g/24hrs)

          -  Patient consent must be appropriately obtained in accordance with applicable local and
             regulatory requirements. Each patient must sign a consent form prior to enrollment in
             the trial to document their willingness to participate.

        Patients who cannot give informed consent (i.e. mentally incompetent patients, or those
        physically incapacitated such as comatose patients) are not to be recruited into the study.
        Patients competent but physically unable to sign the consent form may have the document
        signed by their nearest relative or legal guardian. Each patient will be provided with a
        full explanation of the study before consent is requested.

          -  Patients must be accessible for treatment and follow-up. Patients registered on this
             trial must be treated and followed at the participating centre. This implies there
             must be reasonable geographical limits (for example: 2 hour's driving distance) placed
             on patients being considered for this trial. Investigators must assure themselves that
             the patients registered on this trial will be available for complete documentation of
             the treatment, adverse events, response assessment and follow-up.

          -  Patient is able (i.e. sufficiently fluent) and willing to complete the quality of life
             (EORTC QLQ-C30) in either English or French. The baseline assessment must already have
             been completed. Inability (illiteracy in English or French, loss of sight, or other
             equivalent reason) to complete the questionnaires will not make the patient ineligible
             for the study. However, ability but unwillingness to complete the questionnaires will
             make the patient ineligible. The baseline assessment must be completed within 14 days
             prior to randomization.

          -  In accordance with NCIC CTG policy, protocol treatment is to begin within 5 working
             days of patient randomization.

        Exclusion Criteria:

          -  Patients with a history of other malignancies, except for adequately treated
             non-melanoma skin cancer or solid tumours curatively treated with no evidence of
             disease for ≥ 3 years. (Please call NCIC CTG if any questions about the interpretation
             of this criterion).

          -  Patients who are on immunosuppressive therapy or have known HIV infection or active
             hepatitis B or C.

          -  Patients with active or uncontrolled infections or with serious illnesses or medical
             conditions which would not permit the patient to be managed according to the protocol.

          -  Patients with significant cardiac (including uncontrolled hypertension) or pulmonary
             disease, or active CNS disease or infection.

          -  Patients are not eligible if they have a known hypersensitivity to the study drug(s)
             or their components.

          -  Patients with history of central nervous system metastases or untreated spinal cord
             compression.

          -  Patients who have had prior treatment with oxaliplatin or bevacizumab, who have
             contraindications to treatment with 5FU (for e.g. known DPD deficiency or severe
             cardiac disease), and or neuropathy > grade 1.

          -  Patients who are not sterile unless they use an adequate method of birth control.