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

November 5, 2023 updated by: Mohammed Najeeb Al Hallak

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

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Primary Objectives:

  1. Phase I: To determine the recommended phase 2 dose (RP2D) of gemcitabine, nabpaclitaxel and selinexor for untreated metastatic pancreatic cancer [COMPLETED]
  2. Phase I: To determine the safety profile of gemcitabine, nab-paclitaxel and selinexor [COMPLETED]
  3. Phase II: To test whether the combination of gemcitabine and selinexor improves the median overall survival of patients with metastatic pancreatic cancer who have failed frontline non-gemcitabine containing regimens beyond 5.6 months (median overall survival of patient receiving gemcitabine only based on historical data.

Secondary Objectives:

  1. To determine objective response rate to the combination of gemcitabine and selinexor using Response Evaluation Criteria in Solid Tumors (RECIST) criteria.
  2. To assess safety of selinexor in combination with gemcitabine in phase II portion of the study
  3. To determine progression free survival (PFS) in patients treated with gemcitabine and selinexor
  4. To determine the influence of selinexor and gemcitabine on the nuclear expression and localization of tumor suppressor gene proteins.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
15

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Michigan
      • Detroit, Michigan, United States, 48201
        • Barbara Ann Karmanos Cancer Institute
    • New York
      • Stony Brook, New York, United States, 11794
        • Stony Brook University Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

19 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Group I: Phase Ib (gemcitabine, nab-paclitaxel, selinexor)
Patients receive gemcitabine hydrochloride IV, nab-paclitaxel IV, and selinexor PO on days 1, 8, and 15. Cycles repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.
Other: Laboratory Biomarker Analysis
Correlative studies
Other: Pharmacological Study
Correlative studies
Drug: gemcitabine hydrochloride
Given IV
Other Names:
  • Gemzar
  • dFdC
  • Gemcitabine HCI
  • difluorodeoxycytidine hydrochloride
Drug: Nab paclitaxel
Given IV
Other Names:
  • Abraxane
  • ABI 007
  • Protein-bound Paclitaxel
  • Nanoparticle Paclitaxel,
Drug: Selinexor
Given IV
Other Names:
  • KPT-330
  • SINE KPT-330
  • Xpovio
  • CRM1 nuclear export inhibitor KPT-330
  • selective inhibitor of nuclear export KPT-330
Experimental: Group II: Phase II Group I (gemcitabine, selinexor)
Patients receive gemcitabine hydrochloride IV on days 1, 8, and 15. Patients also receive selinexor PO on days 3, 8, and 15 of cycle 1 and on days 1, 8, and 15 for the subsequent cycles. Cycles repeat every 4 weeks in the absence of disease progression or unacceptable toxicity
Other: Laboratory Biomarker Analysis
Correlative studies
Other: Pharmacological Study
Correlative studies
Drug: gemcitabine hydrochloride
Given IV
Other Names:
  • Gemzar
  • dFdC
  • Gemcitabine HCI
  • difluorodeoxycytidine hydrochloride
Drug: Selinexor
Given IV
Other Names:
  • KPT-330
  • SINE KPT-330
  • Xpovio
  • CRM1 nuclear export inhibitor KPT-330
  • selective inhibitor of nuclear export KPT-330
Experimental: GroupIII: Phase II Group II (gemcitabine, selinexor)
Patients receive gemcitabine hydrochloride IV and selinexor PO on days 1, 8, and 15. Cycles repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.
Other: Laboratory Biomarker Analysis
Correlative studies
Other: Pharmacological Study
Correlative studies
Drug: gemcitabine hydrochloride
Given IV
Other Names:
  • Gemzar
  • dFdC
  • Gemcitabine HCI
  • difluorodeoxycytidine hydrochloride
Drug: Selinexor
Given IV
Other Names:
  • KPT-330
  • SINE KPT-330
  • Xpovio
  • CRM1 nuclear export inhibitor KPT-330
  • selective inhibitor of nuclear export KPT-330

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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.
28 days
Proportion of Patients With a Toxic Event, Graded According to NCI CTCAE Version 4.03
Time Frame: Up to 2 years
The reported output is the proportion of patients that had a toxic event along with the associated 90% Wilson's confidence interval.
Up to 2 years
Overall Survival (Phase II)
Time Frame: Up to 7 months post treatment initiation
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.
Up to 7 months post treatment initiation

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
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
Day 1 of course 1 (before selinexor administration, 1, 2, 4 and 8 hours after selinexor administration) and days 2, 3 and 8
Proportion of Patients With a Response
Time Frame: Up to 2 years
Point and 90% Wilson's confidence intervals will be estimated to describe response rate. If the best observed clinical response was complete response or partial response, we consider that the patient responded.
Up to 2 years
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. Both progression and death are considered events for this analysis.
Up to 2 years

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Change in Gene Expression (Including Forkhead Box Protein O, I-kappaB, Cyclin-dependent Kinase Inhibitor 1B, Par4 and Phosphorylated Signal Transducer and Activator of Transcription 3) (Phase II)
Time Frame: Baseline to up to 2 years
Seven patients in each group will yield a two-sided 90% confidence interval with a distance from the mean change to the limits of 0.75 standard deviation units. A two-sided p-value of 0.10 will be used for all analyses.
Baseline to up to 2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Mohammed Najeeb Al Hallak

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
National Cancer Institute (NCI)

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Mohammed N Al Hallak, M.D., Barbara Ann Karmanos Cancer Institute

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
October 31, 2014

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
November 27, 2021

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
April 5, 2023

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
June 23, 2014

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 26, 2014

First Posted (Estimated)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
June 30, 2014

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
November 7, 2023

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 5, 2023

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
November 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 2013-133
  • NCI-2014-01249 (Other Identifier: CTRP (Clinical Trial Reporting Program))

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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