A Randomized Phase II Study of Reolysin in Combination With FOLFOX6 and Bevacizumab or FOLFOX6 and Bevacizumab Alone in Patients With Metastatic Colorectal Cancer.
- 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
- 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
Previous major surgery is permitted provided that it has been at least 21days prior to
patient randomization and that wound healing has occurred.
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 enrolment and the regimen did not include oxaliplatin or
bevacizumab. Exceptions may be made for low dose chemotherapy given as a radiosensitizing
Patients may have received other therapies including immunotherapy, or with signal
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)
Granulocytes (AGC) ≥ 1.5 x 10^9/L Platelets ≥ 100 x 10^9/L
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 ≤ grade 2 (confirmed on 24 hour urine)
- 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.
- 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
- 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, or are unable to discontinue therapy with acetaminophen.
- Patients with history of central nervous system metastases or untreated spinal cord
- 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.