Phase 2 Study of REOLYSIN® in Combination With Paclitaxel and Carboplatin for Non-Small Cell Lung Cancer With KRAS or EGFR Activation

December 1, 2015 updated by: Oncolytics Biotech

Phase 2 Study of Intravenous Administration of Reovirus Serotype 3 - Dearing Strain (REOLYSIN®) in Combination With Paclitaxel and Carboplatin in Patients With Metastatic or Recurrent Non-Small Cell Lung Cancer Who Have KRAS or EGFR Activated Tumors

The purpose of this Phase 2 study is to investigate whether intravenous administration of a wild type reovirus (REOLYSIN®) in combination with paclitaxel and carboplatin is effective and safe in the treatment of Non-Small Cell Lung Cancer with KRAS or EGFR activation.

Study Overview

Status

Completed

Conditions

Carcinoma, Non-small Cell Lung

Intervention / Treatment

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.

Given the ability of reovirus to replicate and cause oncolysis in Ras-activated cells, the high incidence of K-ras mutations in lung cancers, and the Ras-mediated activation often encountered in EGFR-addicted tumors, the administration of REOLYSIN® in combination with chemotherapy is expected to result in enhanced clinical benefit in non-small cell lung cancer (NSCLC) patients with K-ras mutations and/or EGFR aberrant activation in their tumors. Patients with de novo or acquired EGFR mutations in their tumors that confer resistance to EGFR TKIs (e.g. T790) are expected to benefit as well. This is a single arm, open-label, Phase 2 study of REOLYSIN® given intravenously with paclitaxel and carboplatin every 3 weeks (21 days is defined as a cycle) in NSCLC patients with tumors driven by these pathways.

Paclitaxel at a dose of 175 mg/m2 will be given i.v. as a 3 hour infusion on Day 1 followed by carboplatin given i.v. AUC 5 mg/mL•minute. REOLYSIN® will be given over 60 min on Day 1 (starting after completion of the carboplatin infusion), and on Days 2 - 5. The treatment cycle will be repeated every 21 days.

Patients will receive 4 to 6 cycles of paclitaxel and carboplatin, at the treating physician's discretion according to standard of practice, in conjunction with REOLYSIN®. After completion of the 4 to 6 cycles of paclitaxel and carboplatin, REOLYSIN® may be continued as monotherapy Days 1-5 of each 21 day cycle until there is evidence of disease progression or unacceptable toxicity. Patients may continue to receive therapy under this protocol, provided they have not experienced either progressive disease or unacceptable drug-related toxicity that does not respond to either supportive care or dose reduction.

Study Type

Interventional

Enrollment (Actual)

Phase

Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

United States
- District of Columbia
  - Washington, District of Columbia, United States, 20007
    - Georgetown University Medical Center
- Ohio
  - Columbus, Ohio, United States, 43210
    - The Ohio State University Medical Center, James Cancer Hospital and Solove Research Institute

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

Genders Eligible for Study

All

Description

Inclusion Criteria:

have histologically or cytologically confirmed stage IIIB (pleural effusion; IVA on revised IASLC staging) or stage IV, or recurrent, non-small cell lung cancer with evidence of RAS- or EGFR- activation in their tumors, as defined by EGFR activating mutations in exons 18 to 21, EGFR FISH amplification, or K-ras mutations in exon 2 (codons 12,13,61).
have evidence of measurable disease. For patients previously irradiated, the measurable lesion(s) must be outside of the treated field.
be chemotherapy naïve for their metastatic or recurrent NSCLC. Prior adjuvant chemotherapy or chemo-XRT for treatment of localized disease is allowed, provided it has been ≥ 6 months since the last chemotherapy infusion. Previous radiation for palliative purposes is also allowed, as long as it has been ≥4 weeks from the last dose.
Patients who have been previously treated with EGFR tyrosine kinase inhibitors as their only systemic treatment are eligible, provided this treatment has been discontinued for ≥4 weeks. Patients who have received erlotinib as first line treatment without chemotherapy and experience tumor progression will be eligible.
have NO continuing acute toxic effects (except alopecia) of any prior radiotherapy, chemotherapy, or surgical procedures, i.e., all such effects must have resolved to Common Terminology Criteria for Adverse Events (CTCAE, version 3.0) Grade ≤ 1. Surgery (except biopsies) must have occurred at least 28 days prior to study enrollment.
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 10E9 [SI units 10^9/L]
- Platelets ≥ 100 x10E9 [SI units 10E9/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 ≤ 1.5 x ULN
- AST/ALT ≤ 2.5 x ULN
- Negative pregnancy test for females of childbearing potential.
be willing and able to comply with scheduled visits, the treatment plan, and laboratory tests.

Exclusion Criteria:

Receive concurrent therapy with any other anticancer agent while on study.
Received chemotherapy within 6 months, or radiotherapy or EGFR therapy within 4 weeks, prior to entering the study or have not recovered from adverse events due to agents administered more than 4 weeks earlier.
Have brain metastases. Patients with resected oligometastasis are eligible if post resection MRI demonstrates resolution. Gamma knife treated patients are also eligible, if there are no more than two treated metastases confined to the same area of the brain and a post treatment MRI shows a decrease in the metastases.
Have ≥ grade 2 peripheral neuropathy at baseline.
Have uncontrolled cardiac dysfunction, including a myocardial infarction in the preceding 6 months, or known cardiac ejection fraction < 40%.
Be on immunosuppressive therapy or have known HIV infection or active hepatitis B or C.
Be a pregnant or breast-feeding woman. Female patients of childbearing potential must agree to use effective contraception, must be surgically sterile, or must be postmenopausal. Male patients must agree to use effective contraception or be surgically sterile. Barrier methods are a recommended form of contraception.
Have uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/ social situations that would limit compliance with study requirements.
Have dementia or altered mental status that would prohibit informed consent.
Have any other severe, 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Primary Purpose: Treatment
Allocation: N/A
Interventional Model: Single Group Assignment
Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Determine the objective response rate (complete response (CR) + partial response (PR)) of the treatment regimen in the study population Time Frame: For PR or CR, changes in tumor measurements must be confirmed 4 weeks after the criteria for response are first met.	For PR or CR, changes in tumor measurements must be confirmed 4 weeks after the criteria for response are first met.

Secondary Outcome Measures

Outcome Measure	Time Frame
Determine the median duration of progression-free survival of patients receiving the study treatment. Time Frame: during and following study	during and following study
Determine the median to 1-year survival of patients receiving the study treatment. Time Frame: up to one year	up to one year
Evaluate the safety and tolerability of REOLYSIN® in combination with paclitaxel and carboplatin in this patient population. Time Frame: within 30 days of last dose of REOLYSIN®	within 30 days of last dose of REOLYSIN®
Determine the proportion of patients receiving the above treatment who are alive and free of disease progression at 6 months Time Frame: 6 months	6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Oncolytics Biotech

Investigators

Principal Investigator: Miguel Villalona, MD, Ohio State University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2009

Primary Completion (Actual)

September 1, 2015

Study Completion (Actual)

November 1, 2015

Study Registration Dates

First Submitted

March 12, 2009

First Submitted That Met QC Criteria