Carboplatin and Paclitaxel With or Without Viral Therapy in Treating Patients With Recurrent or Metastatic Pancreatic Cancer
This phase II clinical trial is studying how well giving carboplatin and paclitaxel with or without viral therapy work in treating patients with recurrent or metastatic pancreatic cancer. Drugs used in chemotherapy, such as carboplatin and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Viral therapy may be able to kill tumor cells without damaging normal cells. It is not yet known whether carboplatin and paclitaxel are more effective with viral therapy in treating pancreatic cancer.
Adenocarcinoma of the Pancreas
Recurrent Pancreatic Cancer
Stage IV Pancreatic Cancer
Biological: wild-type reovirus
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A 2-arm Randomized Phase II Study of Carboplatin, Paclitaxel Plus Reovirus Serotype-3 Dearing Strain (Reolysin®) vs. Carboplatin and Paclitaxel in the First Line Treatment of Patients With Recurrent or Metastatic Pancreatic Cancer|
- Progression-free survival [ Time Frame: From study entry to the date of documented progression and/or death, assessed up to 3 years ] [ Designated as safety issue: No ]The progression-free survival distributions between the two arms will be compared using log-rank tests. Progression-free survival curves will be constructed using the Kaplan-Meier product limit method, and additional analyses will be done using the Cox proportional hazards model.
- Overall response rate (partial or complete response) evaluated using the standard RECIST criteria [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]95% confidence intervals will be calculated. Differences in objective response rates between the treatment arms will be assessed using Fisher's exact test.
- Overall survival [ Time Frame: From study entry to the time of death due to any cause, assessed up to 3 years ] [ Designated as safety issue: No ]Evaluated and compared between the two treatment groups using log-rank statistics and graphically using the methods of Kaplan and Meier.
- Toxicity and tolerability defined as adverse events that are classified as either possibly, probably, or definitely related to study treatment, as assessed by NCI CTCAE version 4.0 [ Time Frame: Up to 3 years ] [ Designated as safety issue: Yes ]The incidence of severe (grade 3+) adverse events or toxicities will be described for each treatment arm, but will also be compared between the arms. Fisher's exact tests will be used to quantitatively compare the incidence of severe as well as specific toxicities of interest between the treatment arms and we will graphically assess differences in maximum grades observed for toxicities between the arms.
|Study Start Date:||December 2010|
|Estimated Primary Completion Date:||December 2014 (Final data collection date for primary outcome measure)|
Experimental: Arm I
Patients receive paclitaxel IV over 3 hours and carboplatin IV over 30 minutes on day 1 and wild-type reovirus IV over 60 minutes on days 1-5. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Biological: wild-type reovirus
Other Name: REOLYSINDrug: carboplatin
Other Names:Drug: paclitaxel
Experimental: Arm II
Patients receive paclitaxel and carboplatin as in arm I. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients with disease progression may crossover to arm I.
Other Names:Drug: paclitaxel
I. To assess the improvement in progression-free survival with Reolysin, carboplatin, and paclitaxel relative to carboplatin and paclitaxel alone in patients with recurrent or metastatic pancreatic cancer.
I. To evaluate the safety and tolerability of Reolysin in combination with carboplatin and paclitaxel versus without Reolysin in patients with recurrent or metastatic pancreas cancer.
II. To compare the treatment groups for other efficacy endpoints such as overall response rate and overall survival.
III. To define how the combination of Reolysin and CP modulate factors regulating immunity to reovirus and its persistence in the system circulation of patients with pancreatic cancer.
IV. To prospectively establish and validate the relationship between Ras mutations in tumor samples and response to Reolysin.
OUTLINE: This is a multicenter study. Patients are randomized to 1 of 2 treatment arms.
ARM I: Patients receive paclitaxel intravenously (IV) over 3 hours and carboplatin IV over 30 minutes on day 1 and wild-type reovirus IV over 60 minutes on days 1-5. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
ARM II: Patients receive paclitaxel and carboplatin as in arm I. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients with disease progression may crossover to arm I.
Blood samples and previously collected tumor tissue samples are analyzed for genetic mutations and/or protein levels of the RAS signaling pathway activation and other correlative studies.
After completion of study therapy, patients are followed up at 1 month and then every 2 months thereafter.
|United States, District of Columbia|
|Lombardi Comprehensive Cancer Center at Georgetown University||Recruiting|
|Washington, District of Columbia, United States, 20057|
|Contact: John L. Marshall 202-444-7064 email@example.com|
|Principal Investigator: John L. Marshall|
|United States, Georgia|
|Atlanta, Georgia, United States, 30322|
|Contact: Bassel F. El-Rayes 404-778-1900 firstname.lastname@example.org|
|Principal Investigator: Bassel F. El-Rayes|
|United States, New York|
|Montefiore Medical Center||Recruiting|
|Bronx, New York, United States, 10467-2490|
|Contact: Santiago Aparo 718-920-4826 email@example.com|
|Principal Investigator: Santiago Aparo|
|Memorial Sloan Kettering Cancer Center||Recruiting|
|New York, New York, United States, 10065|
|Contact: Eileen M. O'Reilly 212-639-6672 firstname.lastname@example.org|
|Principal Investigator: Eileen M. O'Reilly|
|United States, Ohio|
|Ohio State University Medical Center||Recruiting|
|Columbus, Ohio, United States, 43210|
|Contact: Tanios S. Bekaii-Saab 614-293-9863 email@example.com|
|Principal Investigator: Tanios S. Bekaii-Saab|
|United States, Oklahoma|
|University of Oklahoma Health Sciences Center||Recruiting|
|Oklahoma City, Oklahoma, United States, 73104|
|Contact: Shubham Pant 405-271-4022 Shubhamfirstname.lastname@example.org|
|Principal Investigator: Shubham Pant|
|Principal Investigator:||Tanios Bekaii-Saab||Ohio State University|