Clinical Trials /

Gemcitabine, Nab-paclitaxel and KPT-330 in Advanced Pancreatic Cancer

NCT02178436

Description:

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

Related Conditions:
  • Pancreatic Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Selinexor, Gemcitabine Hydrochloride, and Paclitaxel Albumin-Stabilized Nanoparticle Formulation in Treating Patients With Metastatic Pancreatic Cancer
  • 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

Clinical Trial IDs

  • ORG STUDY ID: 2013-133
  • SECONDARY ID: NCI-2014-01249
  • SECONDARY ID: 1403012942
  • SECONDARY ID: 2013-133
  • SECONDARY ID: P30CA022453
  • NCT ID: NCT02178436

Conditions

  • Acinar Cell Adenocarcinoma of the Pancreas
  • Duct Cell Adenocarcinoma of the Pancreas
  • Stage IV Pancreatic Cancer

Interventions

DrugSynonymsArms
gemcitabine hydrochloridedFdC, difluorodeoxycytidine hydrochloride, gemcitabine, GemzarGroup I (selinexor, gemcitabine, nab-paclitaxel)
paclitaxel albumin-stabilized nanoparticle formulationABI-007, nab paclitaxel, nab-paclitaxel, nanoparticle albumin-bound paclitaxelGroup I (selinexor, gemcitabine, nab-paclitaxel)
selinexorCRM1 nuclear export inhibitor KPT-330, KPT-330, selective inhibitor of nuclear export KPT-330, SINE KPT-330Group I (selinexor, gemcitabine, nab-paclitaxel)

Purpose

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 Description

      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.
      Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.

      PHASE II: The first 14 patients with liver metastases are randomized to 1 of 2 treatment
      groups. Remaining patients are assigned to Group II.

      GROUP I: Patients receive gemcitabine hydrochloride IV and paclitaxel albumin-stabilized
      nanoparticle formulation IV as in Phase Ib. Beginning day 3 of course 1, patients also
      receive selinexor PO twice weekly (Mondays and Wednesdays) for 4 weeks. Courses repeat every
      4 weeks in the absence of disease progression or unacceptable toxicity.

      GROUP II: Patients receive gemcitabine hydrochloride, paclitaxel albumin-stabilized
      nanoparticle formulation, and selinexor as in Phase Ib.

      After completion of study treatment, patients are followed up for 2 years.
    

Trial Arms

NameTypeDescriptionInterventions
Group I (selinexor, gemcitabine, nab-paclitaxel)ExperimentalPatients receive gemcitabine hydrochloride IV and paclitaxel albumin-stabilized nanoparticle formulation IV once weekly (Mondays) for 3 weeks. Beginning day 3 of course 1, patients also receive selinexor PO twice weekly (Mondays and Wednesdays) for 4 weeks. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.
  • gemcitabine hydrochloride
  • paclitaxel albumin-stabilized nanoparticle formulation
  • selinexor
Group II (selinexor, gemcitabine, nab-paclitaxel)ExperimentalPatients receive gemcitabine hydrochloride IV and paclitaxel albumin-stabilized nanoparticle formulation IV once weekly (Mondays) for 3 weeks. Patients also receive selinexor PO twice weekly (Mondays and Wednesdays) for 4 weeks. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.
  • gemcitabine hydrochloride
  • paclitaxel albumin-stabilized nanoparticle formulation
  • selinexor

Eligibility Criteria

        Inclusion Criteria:

          -  Written informed consent in accordance with federal, local, and institutional
             guidelines

          -  Patients with metastatic pancreatic adenocarcinoma not treated with chemotherapy for
             metastatic disease

          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0-1

          -  Absolute neutrophil count (ANC) >= 1500/mm^3

          -  Platelet count >= 100,000/mm^3

          -  Bilirubin < 2 times the upper limit of normal (ULN) (except patients with Gilbert's
             syndrome who must have a total bilirubin of < 3 times ULN)

          -  Alanine aminotransferase (ALT) < 2.5 times ULN

          -  Serum creatinine =< 1.5 mg/dL

          -  Serum albumin >= 3.0 g/dL

          -  Female patients of child-bearing potential must agree to use dual methods of
             contraception and have a negative serum pregnancy test at screening, and male
             patients must use an effective barrier method of contraception if sexually active
             with a female of child-bearing potential; acceptable methods of contraception are
             condoms with contraceptive foam, oral, implantable or injectable contraceptives,
             contraceptive patch, intrauterine device, diaphragm with spermicidal gel, or a sexual
             partner who is surgically sterilized or post-menopausal; for both male and female
             patients, effective methods of contraception must be used throughout the study and
             for three months following the last dose

          -  Patients with history of previously treated malignancies who have no evidence of
             disease for last five years are allowed to participate

        Exclusion Criteria:

          -  Patients who are pregnant or lactating

          -  Radiation, chemotherapy, or immunotherapy or any other anticancer therapy =< 3 weeks
             prior to cycle 1 day 1; mitomycin C or radio-immunotherapy 6 weeks prior to cycle 1
             day 1

          -  Major surgery within four weeks before cycle 1 day 1

          -  Unstable cardiovascular function:

               -  Symptomatic ischemia, or

               -  Uncontrolled clinically significant conduction abnormalities (e.g.: ventricular
                  tachycardia on antiarrhythmics are excluded and 1st degree atrioventricular [AV]
                  block or asymptomatic left anterior fascicular block [LAFB]/right bundle branch
                  block [RBBB] will not be excluded), or

               -  Congestive heart failure (CHF) of New York Heart Association (NYHA) class >= 3,
                  or

               -  Myocardial infarction (MI) within 3 months of cycle 1 day 1 dose

          -  Uncontrolled active infection requiring parenteral antibiotics, antivirals, or
             antifungals within one week prior to first dose

          -  Known to be HIV seropositive who are on anti-HIV drugs because of the unknown
             interactions between these drugs and the study agents

          -  Known active hepatitis A, B, or C infection; or known to be positive for hepatitis C
             virus (HCV) ribonucleic acid (RNA) or HBsAg (hepatitis B virus [HBV] surface antigen)

          -  Patients with active central nervous system (CNS) malignancy; asymptomatic small
             lesions are not considered active; treated lesions may be considered inactive if they
             are stable for at least 3 months

          -  Patients with significantly diseased or obstructed gastrointestinal tract or
             uncontrolled vomiting or diarrhea

          -  Grade >= 2 peripheral neuropathy within 14 days prior to cycle 1 day 1

          -  History of seizures, movement disorders or cerebrovascular accident within the past 5
             years prior to cycle 1 day 1

          -  Patients with muscular degeneration, uncontrolled glaucoma, or markedly decreased
             visual acuity based on physician's assessment

          -  Serious psychiatric or medical conditions that could interfere with treatment

          -  Participation in an investigational anti-cancer study within 3 weeks prior to cycle 1
             day 1

          -  Concurrent therapy with approved or investigational anticancer therapeutic

          -  Presence of clinically significant ascites
      
Maximum Eligible Age:N/A
Minimum Eligible Age:19 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Maximum tolerated dose (MTD) of selinexor, gemcitabine hydrochloride, and paclitaxel albumin-stabilized nanoparticle formulation combination (Phase Ib)
Time Frame:28 days
Safety Issue:
Description: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.

Secondary Outcome Measures

Measure: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
Safety Issue:
Description:Pharmacodynamics of selinexor in combination with gemcitabine hydrochloride and paclitaxel albumin-stabilized nanoparticle formulation
Measure:Response rate
Time Frame:Up to 2 years
Safety Issue:
Description:Point and 90% Wilson's confidence intervals will be estimated to describe response rate.
Measure:Progression free survival (Phase II)
Time Frame:Up to 2 years
Safety Issue:
Description: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.

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Suspended
Lead Sponsor:Barbara Ann Karmanos Cancer Institute

Last Updated

April 5, 2017