Clinical Trial: Selinexor, Gemcitabine Hydrochloride, and Paclitaxel Albumin-Stabilized Nanoparticle Formulation in Treating Patients With Metastatic Pancreatic Cancer

Study Status: Suspended
Recruit Status: Suspended
Study Type: Interventional

Official Title: A Phase Ib/II Study of the Selective Inhibitor of Nuclear Export (SINE) KPT-330, Gemcitabine and Nab-Paclitaxel in Patients With Metastatic Pancreatic Cancer

Brief Summary: This partially randomized phase Ib/II trial studies the side effects and best dose of selinexor when given together with gemcitabine hydrochloride and paclitaxel albumin-stabilized nanoparticle formulation and to see how well they work in treating patients with pancreatic cancer that has spread to other parts of the body. Drugs used in chemotherapy, such as selinexor, gemcitabine hydrochloride and paclitaxel albumin-stabilized nanoparticle formulation, 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.

Detailed Summary:

PRIMARY OBJECTIVES:

I. To determine the recommended phase 2 dose (RP2D) of gemcitabine (gemcitabine hydrochloride), nab-paclitaxel (paclitaxel albumin-stabilized nanoparticle formulation) and KPT-330 (selinexor) for untreated metastatic pancreatic cancer.

II. To determine the safety profile of gemcitabine, nab-paclitaxel and KPT-330. III. To test whether gemcitabine, nab-paclitaxel and KPT-330 improves overall survival as compared to historical controls comprising of patients with metastatic pancreatic cancer.

SECONDARY OBJECTIVES:

I. To determine objective response rate to combination of gemcitabine, nab-paclitaxel and KPT-330 using Response Evaluation Criteria In Solid Tumors (RECIST) criteria.

II. To confirm safety of KPT-330 at the RP2D in combination with gemcitabine and nab-paclitaxel in phase II arm of the study.

III. To determine progression free survival (PFS) in phase II cohort treated with gemcitabine, nab-paclitaxel and KPT-330.

IV. To determine the influence of KP-330, gemcitabine and nab-paclitaxel on the nuclear expression and localization of tumor suppressor gene proteins.

OUTLINE: This is a phase Ib, dose-escalation study of selinexor followed by phase II.

PHASE IB:

Patients receive gemcitabine hydrochloride intravenously (IV) and paclitaxel albumin-stabilized nanoparticle formulation IV once weekly (Mondays) for 3 weeks. Patients also receive selinexor orally (PO) twice weekly (Mondays and Wednesdays) for 4 weeks
Sponsor: Barbara Ann Karmanos Cancer Institute

Current Primary Outcome:

  • Maximum tolerated dose (MTD) of selinexor, gemcitabine hydrochloride, and paclitaxel albumin-stabilized nanoparticle formulation combination (Phase Ib) [ Time Frame: 28 days ]
    MTD is defined as the lowest dose for which less than a third of patients experience a dose limiting toxicity graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 4.03.
  • Incidence of toxicity graded according to NCI CTCAE version 4.03 (Phase II) [ Time Frame: Up to 2 years ]
    Point and 90% Wilson's confidence intervals will be estimated to describe toxicity rate.
  • Overall survival (Phase II) [ Time Frame: Up to 2 years ]
    Estimated on an intention-to-treat basis (using all registered patients), and on a response-evaluable basis (using all patients who completed at least one 4-week treatment cycle) using the Kaplan-Meier method.


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Effects the study drug combination has on participants [ Time Frame: Day 1 of course 1 (before selinexor administration, 1, 2, 4 and 8 hours after selinexor administration) and days 2, 3 and 8 ]
    Pharmacodynamics of selinexor in combination with gemcitabine hydrochloride and paclitaxel albumin-stabilized nanoparticle formulation
  • Response rate [ Time Frame: Up to 2 years ]
    Point and 90% Wilson's confidence intervals will be estimated to describe response rate.
  • Progression free survival (Phase II) [ Time Frame: Up to 2 years ]
    Estimated on an intention-to-treat basis (using all registered patients), and on a response-evaluable basis (using all patients who completed at least one 4-week treatment cycle) using the Kaplan-Meier method.


Original Secondary Outcome: Same as current

Information By: Barbara Ann Karmanos Cancer Institute

Dates:
Date Received: June 23, 2014
Date Started: October 2014
Date Completion: December 2017
Last Updated: April 5, 2017
Last Verified: April 2017