Phase 2 Study of REOLYSIN® in Combination With Paclitaxel and Carboplatin for Non-Small Cell Lung Cancer With KRAS or EGFR Activation
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT00861627|
Recruitment Status : Completed
First Posted : March 13, 2009
Last Update Posted : December 2, 2015
|Condition or disease||Intervention/treatment||Phase|
|Carcinoma, Non-small Cell Lung||Biological: REOLYSIN® Drug: Carboplatin Drug: Paclitaxel||Phase 2|
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 (Clinical Trial)|
|Actual Enrollment :||37 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|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|
|Study Start Date :||March 2009|
|Actual Primary Completion Date :||September 2015|
|Actual Study Completion Date :||November 2015|
- Biological: REOLYSIN®
3x10E10 TCID50, 1 hour intravenous infusion, administered on Days 1, 2, 3, 4 and 5 of a 21 day cycleOther Name: reovirus serotype 3 Dearing Strain
- Drug: Carboplatin
5 AUC mg/mL min, 30 min intravenous infusion, given on Day 1 of a 21 day cycle
- Drug: Paclitaxel
175 mg/m2, 3 hour intravenous infusion, given on Day 1 of 21 day cycle
- 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. ]
- Determine the median duration of progression-free survival of patients receiving the study treatment. [ Time Frame: during and following study ]
- Determine the median to 1-year survival of patients receiving the study treatment. [ Time Frame: 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® ]
- Determine the proportion of patients receiving the above treatment who are alive and free of disease progression at 6 months [ Time Frame: 6 months ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00861627
|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|