Study of REOLYSIN® in Combination With FOLFIRI and Bevacizumab in FOLFIRI Naive Patients With KRAS Mutant Metastatic Colorectal Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2014 by Oncolytics Biotech
Sponsor:
Collaborator:
Montefiore Medical Center
Information provided by (Responsible Party):
Oncolytics Biotech
ClinicalTrials.gov Identifier:
NCT01274624
First received: January 7, 2011
Last updated: February 5, 2014
Last verified: February 2014
  Purpose

This is a Phase 1 dose-escalation study with three dose levels to determine the maximum tolerated dose of REOLYSIN® combined with FOLFIRI and bevacizumab.


Condition Intervention Phase
KRAS Mutant Metastatic Colorectal Cancer
Biological: REOLYSIN®
Drug: Irinotecan
Drug: Leucovorin
Drug: Fluorouracil (5-FU)
Drug: Bevacizumab
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Multicenter Phase 1 Study of Intravenous Administration of REOLYSIN® (Reovirus Type 3 Dearing) in Combination With Irinotecan/Fluorouracil/Leucovorin (FOLFIRI) and Bevacizumab in FOLFIRI Naive Patients With KRAS Mutant Metastatic Colorectal Cancer

Resource links provided by NLM:


Further study details as provided by Oncolytics Biotech:

Primary Outcome Measures:
  • Dose limiting toxicity to define maximum tolerated dose and recommended Phase 2 dose [ Time Frame: During the first cycle of treatment (4 week cycle) ] [ Designated as safety issue: Yes ]
  • Pharmacokinetic parameters for irinotecan and 5-FU when combined with REOLYSIN® [ Time Frame: During the first cycle of treatment (4 week cycle) ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • CEA and Objective Response, Clinical Benefit Rate (PR, CR, SD), progression-free survival, and overall survival (PFS and OS) [ Time Frame: Assessed every 8 weeks until disease progression or death ] [ Designated as safety issue: No ]
  • Safety and tolerability of REOLYSIN® when administered in combination with FOLFIRI and bevacizumab [ Time Frame: During study and within 30 days of the last dose of REOLYSIN ] [ Designated as safety issue: Yes ]
  • Correlative studies including determination of specific genetic mutations and aberrant signalling pathways from tumor tissue to identify novel biomarkers of response and efficacy [ Time Frame: During and within 30 days of the last dose of REOLYSIN® ] [ Designated as safety issue: No ]
  • In vitro studies in human-derived colorectal cancer cells including the isogenic cell lines, to study the mechanism and scientific basis of synergy between irinotecan and reovirus [ Time Frame: During study and within 30 days of the last dose of REOLYSIN® ] [ Designated as safety issue: No ]

Estimated Enrollment: 20
Study Start Date: December 2010
Estimated Study Completion Date: October 2015
Estimated Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)
Intervention Details:
    Biological: REOLYSIN®
    1 hour intravenous infusion administered on Days 1, 2, 3, 4, and 5 every 4 weeks.
    Other Name: Reovirus serotype 3 Dearing Strain
    Drug: Irinotecan
    90-minute intravenous infusion on Day 1 every 2 weeks. Dose levels of 125 mg/m2, 150 mg/m2, 150 mg/m2, 180 mg/m2.
    Drug: Leucovorin
    2-hour infusion of 400 mg/m2 on Day 1 every 2 weeks.
    Drug: Fluorouracil (5-FU)
    400 mg/m2 intravenous bolus followed by 2400 mg/m2 as a continuous intravenous infusion over 46 hours administered on Day 1 every 2 weeks.
    Drug: Bevacizumab
    30, 60 or 90 minute infusion on Day 1 every 2 weeks. Dose level 5 mg/kg.
Detailed Description:

Reovirus Serotype 3 - Dearing Strain (REOLYSIN®) is a naturally occurring, ubiquitous, non-enveloped human reovirus. Reovirus has been shown to replicate selectively in Ras-transformed cells causing cell lysis. Activating mutations in ras or mutation in oncogenes signaling through the ras pathway may occur in as many as 80% of human tumors. The specificity of the reovirus for Ras-transformed cells, coupled with its relatively nonpathogenic nature in humans, makes it an attractive anti-cancer therapy candidate. Eligible patients for this study include those with histologically confirmed cancer of the colon or rectum with Kras mutation and measurable disease.

Cetuximab and panitumumab have shown to be ineffective in patients whose tumors have a KRAS mutation. Therefore, currently, for patients with a KRAS mutation, the only option after failure of front-line therapy is irinotecan or FOLFIRI. Over the past year, two randomized phase III trials have demonstrated that OS and PFS for these patients increase when bevacizumab is combined with the standard FOLFIRI therapy.

The trial is a Phase I dose escalation study with four dose levels, comprising cohorts of three to six patients, to determine a maximum tolerated dose and dose-limiting toxicities with the combination of REOLYSIN®, bevacizumab, and FOLFIRI. FOLFIRI and bevacizumab will be administered on the first day of a two week (14-day) cycle, while REOLYSIN® will be administered on days one through five of a four week (28-day) cycle.

The study is expected to enroll 20 to 32 patients.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria: Each patient MUST:

  • Have histologically confirmed cancer of the colon or rectum with radiologically documented and measurable metastases (high CEA alone is insufficient for study entry).
  • Have received 3 or fewer regimens in the metastatic setting.
  • Not have received prior FOLFIRI or irinotecan in the metastatic setting.
  • Have his/her tumor assessed for KRAS status and found to be mutation positive.
  • Have NO continuing acute toxic effects (except alopecia) of any prior radiotherapy, chemotherapy, or surgical procedures, i.e., all such effects must have resolved.
  • Have an ECOG Performance Score of ≤ 2.
  • Have a life expectancy of at least 3 months.
  • Have baseline laboratory results as follows:

    • Absolute neutrophil count (ANC) ≥ 1.5 x 10^9 [SI unit 10^9/L]
    • Platelets ≥ 100 x10^9 [SI units 10^9/L] (without platelet transfusion)
    • Hemoglobin ≥ 9.0 g/dL [SI units gm/L] (with or without RBC transfusion)
    • Serum creatinine ≤ 1.5 x upper limit of normal (ULN)
    • Bilirubin ≤ ULN
    • AST/ALT ≤ 2.5 x ULN (≤ 5 x ULN if with liver metastases)
    • Negative pregnancy test for females with childbearing potential.
  • Have signed an informed consent indicating that the patient is aware of the neoplastic nature of their disease and have been informed of the procedures of the protocol, the experimental nature of the therapy, alternatives, potential benefits, side effects, risks, and discomforts.
  • Be willing and able to comply with scheduled visits, the treatment plan, and laboratory tests.
  • Be medically eligible to receive bevacizumab

Exclusion Criteria: No patient may:

  • Receive concurrent therapy with any other investigational anticancer agent while on study.
  • Have previously received irinotecan or FOLFIRI in the metastatic setting (patient is eligible if he/she had received irinotecan or FOLFIRI as adjuvant therapy more than 6 months before entry into the study)
  • Have brain metastases.
  • Be on immunosuppressive therapy or have known HIV infection or active hepatitis B or C.
  • Have received chemotherapy, radiotherapy, immunotherapy or hormonal therapy or had surgery (except biopsies) within 28 days prior to receiving the study drug.
  • Be a pregnant or breast-feeding woman. Female patients of childbearing potential must agree to use effective contraception, be surgically sterile, or be postmenopausal. Male patients must agree to use effective contraception or be surgically sterile. Barrier methods are a recommended form of contraception.
  • Have clinically significant cardiac disease (New York Heart Association, Class III or IV) including pre-existing arrhythmia, uncontrolled angina pectoris, myocardial infarction within 1 year prior to study entry, or Grade 2 or higher compromised left ventricular ejection fraction.
  • Have dementia or altered mental status that would prohibit informed consent.
  • Have any other acute, or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration or may interfere with the interpretation of study results and, in the judgment of the Principal Investigator, would make the patient inappropriate for this study.
  • Have uncontrolled hypertension, proteinuria, or recent major surgery (all clinical parameters related to bevacizumab use). Any other clinical parameter considered important should be discussed with the medical monitor.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01274624

Locations
United States, New York
Montefiore Medical Center/Albert Einstein College of Medicine Recruiting
Bronx, New York, United States, 10461
Contact: Mohammed Ghalib, MD    718-405-8515    mhghalib@montefiore.org   
Principal Investigator: Sanjay Goel, MD         
New York Presbyterian Hospital/ Weill Cornell Medical College Recruiting
New York, New York, United States, 10065
Contact: June Greenberg    212-746-2651    jdg2002@med.cornell.edu   
Principal Investigator: Alison Ocean, MD         
United States, Ohio
The Ohio State University Recruiting
Columbus, Ohio, United States, 43210
Contact: Tanios Bekaii-Saab, MD    614-293-4372    Tanios.Saab@osumc.edu   
Principal Investigator: Tanios Bekaii-Saab, MD         
Sponsors and Collaborators
Oncolytics Biotech
Montefiore Medical Center
  More Information

No publications provided

Responsible Party: Oncolytics Biotech
ClinicalTrials.gov Identifier: NCT01274624     History of Changes
Other Study ID Numbers: REO 022
Study First Received: January 7, 2011
Last Updated: February 5, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Oncolytics Biotech:
Colorectal
Cancer
REOLYSIN®
Chemotherapy
FOLFIRI
Reovirus
Oncolytic virus
Fluorouracil
Irinotecan
Leucovorin
Bevacizumab

Additional relevant MeSH terms:
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Fluorouracil
Irinotecan
Bevacizumab
Leucovorin
Levoleucovorin
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antimetabolites, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Vitamin B Complex
Vitamins
Micronutrients
Growth Substances
Antidotes

ClinicalTrials.gov processed this record on August 21, 2014