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

NCT01274624 | Completed Phase 1

• 1 other identifier: REO 022
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

KRAS Mutant Metastatic Colorectal Cancer

Keywords

Colorectal; Cancer; REOLYSIN®; Chemotherapy; FOLFIRI; Reovirus; Oncolytic virus; Fluorouracil; Irinotecan; Leucovorin; Bevacizumab

Outcome Measures

Primary Outcomes (2)

• Dose limiting toxicity to define maximum tolerated dose and recommended Phase 2 dose

  During the first cycle of treatment (4 week cycle)

• Pharmacokinetic parameters for irinotecan and 5-FU when combined with REOLYSIN®

  During the first cycle of treatment (4 week cycle)

Secondary Outcomes (4)

• CEA and Objective Response, Clinical Benefit Rate (PR, CR, SD), progression-free survival, and overall survival (PFS and OS)

  Assessed every 8 weeks until disease progression or death

• Safety and tolerability of REOLYSIN® when administered in combination with FOLFIRI and bevacizumab

  During study and within 30 days of the last dose of REOLYSIN

• Correlative studies including determination of specific genetic mutations and aberrant signalling pathways from tumor tissue to identify novel biomarkers of response and efficacy

  During and within 30 days of the last dose of REOLYSIN®

• 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

  During study and within 30 days of the last dose of REOLYSIN®

Interventions

REOLYSIN® BIOLOGICAL

1 hour intravenous infusion administered on Days 1, 2, 3, 4, and 5 every 4 weeks.

Also known as: Reovirus serotype 3 Dearing Strain

Irinotecan DRUG

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.

Leucovorin DRUG

2-hour infusion of 400 mg/m2 on Day 1 every 2 weeks.

Fluorouracil (5-FU) DRUG

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.

Bevacizumab DRUG

30, 60 or 90 minute infusion on Day 1 every 2 weeks. Dose level 5 mg/kg.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 an oxaliplatin-based chemotherapy regimen in the metastatic setting or relapsed within 6 months of completion of adjuvant therapy containing oxaliplatin.
• 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 been resolved.
• Be at least 18 years of age.
• 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 liver metastases)

You may not qualify if:

• 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 \>20 Gy of radiation to the pelvis.
• Have received chemotherapy, immunotherapy, hormonal therapy or had major surgery within 28 days; or received radiotherapy within 14 days; or minor surgery within 7 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.

Sponsors & Collaborators

• Oncolytics Biotech: lead
• Montefiore Medical Center: collaborator

Study Sites (2)

New York Presbyterian Hospital/ Weill Cornell Medical College

New York, New York, 10065, United States

Location

Montefiore Medical Center/Albert Einstein College of Medicine

The Bronx, New York, 10461, United States

Location

MeSH Terms

Conditions

Neoplasms

Interventions

reolysin; Irinotecan; Leucovorin; Fluorouracil; Bevacizumab

Intervention Hierarchy (Ancestors)

Camptothecin; Alkaloids; Heterocyclic Compounds; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 7, 2011
• First Posted: January 11, 2011
• Study Start: December 1, 2010
• Primary Completion: February 1, 2018
• Study Completion: November 1, 2018
• Last Updated: December 19, 2018

Record last verified: 2018-12

Locations

US (2)