Clinical Trial: Carboplatin and Paclitaxel With or Without Viral Therapy in Treating Patients With Recurrent or Metastatic Pancreatic Cancer

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

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

Brief Summary: This phase II trial studies how well carboplatin and paclitaxel with or without viral therapy works in treating patients with pancreatic cancer that has come back or has spread to other places in the body. 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, by stopping them from dividing, or by stopping them from spreading. 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 or without viral therapy in treating pancreatic cancer.

Detailed Summary:

PRIMARY OBJECTIVES:

I. To assess the improvement in progression-free survival with Reolysin (wild-type reovirus), carboplatin, and paclitaxel relative to carboplatin and paclitaxel alone in patients with recurrent or metastatic pancreatic cancer.

SECONDARY OBJECTIVES:

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 carboplatin and paclitaxel (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: 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.

After comp
Sponsor: National Cancer Institute (NCI)

Current Primary Outcome: Progression-free survival using RECIST v. 1.1 [ Time Frame: From study entry to the date of documented progression and/or death, assessed up to 4 years ]

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.


Original Primary Outcome: Progression-free survival of patients treated with Reolysin®, carboplatin, and paclitaxel relative to carboplatin and paclitaxel alone

Current Secondary Outcome:

  • Incidence of severe (grade 3+) 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 4 years ]
    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.
  • Overall response rate (partial or complete response) evaluated using the standard RECIST v. 1.1 [ Time Frame: Up to 4 years ]
    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 4 years ]
    Evaluated and compared between the two treatment groups using log-rank statistics and graphically using the methods of Kaplan and Meier.


Original Secondary Outcome:

  • Overall response rate (partial or complete response)
  • Overall survival
  • Toxicity and tolerability as assessed by NCI CTCAE v 4.0


Information By: National Cancer Institute (NCI)

Dates:
Date Received: January 18, 2011
Date Started: December 2010
Date Completion:
Last Updated: April 24, 2017
Last Verified: April 2017