Phase 2 Study of REOLYSIN® in Combination With Paclitaxel and Carboplatin for Non-Small Cell Lung Cancer With KRAS or EGFR Activation
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.
Carcinoma, Non-small Cell Lung
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||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|
- 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. ] [ Designated as safety issue: No ]
- Determine the median duration of progression-free survival of patients receiving the study treatment. [ Time Frame: during and following study ] [ Designated as safety issue: No ]
- Determine the median to 1-year survival of patients receiving the study treatment. [ Time Frame: up to one year ] [ Designated as safety issue: No ]
- 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® ] [ Designated as safety issue: Yes ]
- Determine the proportion of patients receiving the above treatment who are alive and free of disease progression at 6 months [ Time Frame: 6 months ] [ Designated as safety issue: No ]
|Study Start Date:||March 2009|
|Estimated Study Completion Date:||September 2013|
|Estimated Primary Completion Date:||March 2013 (Final data collection date for primary outcome measure)|
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.
|United States, District of Columbia|
|Georgetown University Medical Center|
|Washington, District of Columbia, United States, 20007|
|United States, Ohio|
|The Ohio State University Medical Center, James Cancer Hospital and Solove Research Institute|
|Columbus, Ohio, United States, 43210|
|Principal Investigator:||Miguel Villalona, MD||Ohio State University|