Reolysin in Combination With FOLFOX6 and Bevacizumab or FOLFOX6 and Bevacizumab Alone in Metastatic Colorectal Cancer

• ClinicalTrials.gov Identifier: NCT01622543
• Recruitment Status: Completed
• First Posted: June 19, 2012
• Results First Posted: December 13, 2019
• Last Update Posted: August 23, 2023
• Sponsor: Canadian Cancer Trials Group
• Collaborator: Oncolytics Biotech
• Information provided by (Responsible Party): Canadian Cancer Trials Group

Tracking Information

• First Submitted Date: June 12, 2012
• First Posted Date: June 19, 2012
• Results First Submitted Date: June 26, 2019
• Results First Posted Date: December 13, 2019
• Last Update Posted Date: August 23, 2023
• Actual Study Start Date: October 26, 2012
• Actual Primary Completion Date: January 18, 2017 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 25, 2019)

Progression Free Survival [ Time Frame: 19 months ]

Time from the day of randomization until the first observation of objective disease relapse or progression, or the appearance of new lesions or death due to any cause. If a patient had not relapsed/progressed or died, PFS was censored on the date of last disease assessment defined as the earliest test date of target lesion or non-target lesions (if patient had no target lesions). Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

Original Primary Outcome Measures (submitted: June 14, 2012)

Progression free survival [ Time Frame: 19 months ]

Effect of reolysin in combination with standard FOLFOX6 chemotherapy on the progression free survival of patients with advanced or metastatic colorectal cancer.

Current Secondary Outcome Measures (submitted: November 25, 2019)

• Changes in CEA Levels [ Time Frame: Baseline and at 28 weeks ]
  Changes in CEA level from baseline to week 28 during treatment.
• Objective Response Rate [ Time Frame: 19 months ]
  Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Objective Response Rate =Proportion of (CR + PR) observed over all randomized patients.
• Overall Survival [ Time Frame: From date of randomization to death from any cause or censored at the time of last known alive, assessed up to 49 months ]
  Time from randomization to death from any cause or censored at the time of last known alive

Original Secondary Outcome Measures (submitted: June 14, 2012)

• Changes in CEA levels [ Time Frame: Baseline and at 19 months ]
  To investigate additional potential measures of efficacy.
• Objective response rate [ Time Frame: 19 months ]
  To investigate additional potential measures of efficacy
• Overall survival [ Time Frame: 19 months ]
  The effect of both treatments on overall survival
• Molecular response [ Time Frame: 19 months ]
  Potential molecular factors predictive of response by assessment of archival tumour tissue (including KRAS status)
• Quality of Life [ Time Frame: 19 months ]
  To explore the Quality of Life (as measured by the EORTC QLQC30).

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Reolysin in Combination With FOLFOX6 and Bevacizumab or FOLFOX6 and Bevacizumab Alone in Metastatic Colorectal Cancer
• Official Title: A Randomized Phase II Study of Reolysin in Combination With FOLFOX6 and Bevacizumab or FOLFOX6 and Bevacizumab Alone in Patients With Metastatic Colorectal Cancer.
• Brief 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.
• Detailed Description: Researchers doing this study also want to evaluate the side effects of reolysin when given together with FOLFOX6/ bevacizumab.
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Colorectal Cancer

Intervention

• Drug: Folfox plus Bevacizumab and reolysin
  FOLFOX6/bevacizumab given every 14 days plus reolysin days 1-5 on cycles 1, 2, 4, 6, 8 and alternate cycles thereafter
• Drug: Folfox plus Bevacizumab
  FOLFOX6/bevacizumab given every 14 days.

Study Arms

• Active Comparator: Folfox plus Bevacizumab and Reolysin
  Intervention: Drug: Folfox plus Bevacizumab and reolysin
• Active Comparator: Folfox plus Bevacizumab
  Intervention: Drug: Folfox plus Bevacizumab

Publications *

• Jonker DJ, Tang PA, Kennecke H, Welch SA, Cripps MC, Asmis T, Chalchal H, Tomiak A, Lim H, Ko YJ, Chen EX, Alcindor T, Goffin JR, Korpanty GJ, Feilotter H, Tsao MS, Theis A, Tu D, Seymour L. A Randomized Phase II Study of FOLFOX6/Bevacizumab With or Without Pelareorep in Patients With Metastatic Colorectal Cancer: IND.210, a Canadian Cancer Trials Group Trial. Clin Colorectal Cancer. 2018 Sep;17(3):231-239.e7. doi: 10.1016/j.clcc.2018.03.001. Epub 2018 Mar 8.
• Provencher DM, Gallagher CJ, Parulekar WR, Ledermann JA, Armstrong DK, Brundage M, Gourley C, Romero I, Gonzalez-Martin A, Feeney M, Bessette P, Hall M, Weberpals JI, Hall G, Lau SK, Gauthier P, Fung-Kee-Fung M, Eisenhauer EA, Winch C, Tu D, MacKay HJ. OV21/PETROC: a randomized Gynecologic Cancer Intergroup phase II study of intraperitoneal versus intravenous chemotherapy following neoadjuvant chemotherapy and optimal debulking surgery in epithelial ovarian cancer. Ann Oncol. 2018 Feb 1;29(2):431-438. doi: 10.1093/annonc/mdx754.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: February 13, 2015): 109
• Original Estimated Enrollment (submitted: June 14, 2012): 100
• Actual Study Completion Date: September 12, 2018
• Actual Primary Completion Date: January 18, 2017 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Canada

Administrative Information

• NCT Number: NCT01622543
• Other Study ID Numbers: I210
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Canadian Cancer Trials Group
• Original Responsible Party: NCIC Clinical Trials Group
• Current Study Sponsor: Canadian Cancer Trials Group
• Original Study Sponsor: NCIC Clinical Trials Group
• Collaborators: Oncolytics Biotech

Investigators

• Study Chair: Derek Jonker; Ottawa Health Research Institute - General Division
• Study Chair: Patricia Tang; Tom Baker Cancer Centre, Calgary, Canada

• PRS Account: Canadian Cancer Trials Group
• Verification Date: March 2020