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Acinar Cell Adenocarcinoma of the PancreasPhase 1/2NCT02178436

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

A Phase 1/2 study testing gemcitabine hydrochloride, Selinexor and Pharmacological Study in people with Acinar Cell Adenocarcinoma of the Pancreas and Duct Cell Adenocarcinoma of the Pancreas, run by Mohammed Najeeb Al Hallak at 2 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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). Read more about this study

Who is it for?
Ages 19 years and older
What is being tested?
gemcitabine hydrochloride, Selinexor and Pharmacological Study
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
15 participants
Where
2 sitesUnited States
Study dates
31 Oct 2014to 5 Apr 2023
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 19 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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)
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  • 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

Who cannot join

  • 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
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  • 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

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • Barbara Ann Karmanos Cancer Institute

    Detroit, Michigan, 48201

  • Stony Brook University Cancer Center

    Stony Brook, New York, 11794

Other trials in United States

About this study

Official title: 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.

Read the 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.
Being tested
gemcitabine hydrochloride, Selinexor, Pharmacological Study, Laboratory Biomarker Analysis, Nab paclitaxel
Medical subject headings
Pancreatic Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • gemcitabine hydrochlorideDrug

    Also called dFdC, difluorodeoxycytidine hydrochloride, Gemcitabine HCI, Gemzar

    Given IV

  • SelinexorDrug

    Also called KPT-330, Xpovio, CRM1 nuclear export inhibitor KPT-330, selective inhibitor of nuclear export KPT-330

    Given IV

  • Pharmacological StudyOther

    Correlative studies

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • Nab paclitaxelDrug

    Also called ABI 007, Abraxane, Protein-bound Paclitaxel, Nanoparticle Paclitaxel,

    Given IV

Study groups in NCT02178436
Study groupRoleWhat they receive
Group I: Phase Ib (gemcitabine, nab-paclitaxel, selinexor)ExperimentalPatients 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.
Receives: Drug: gemcitabine hydrochloride; Drug: Selinexor; Other: Pharmacological Study; Other: Laboratory Biomarker Analysis; Drug: Nab paclitaxel
Group II: Phase II Group I (gemcitabine, selinexor)ExperimentalPatients 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
Receives: Drug: gemcitabine hydrochloride; Drug: Selinexor; Other: Pharmacological Study; Other: Laboratory Biomarker Analysis
GroupIII: Phase II Group II (gemcitabine, selinexor)ExperimentalPatients 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.
Receives: Drug: gemcitabine hydrochloride; Drug: Selinexor; Other: Pharmacological Study; Other: Laboratory Biomarker Analysis

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Maximum Tolerated Dose (MTD) of Selinexor, Gemcitabine Hydrochloride, and Paclitaxel Albumin-stabilized Nanoparticle Formulation Combination (Phase Ib)

    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.

    Measured: 28 days

  2. Proportion of Patients With a Toxic Event, Graded According to NCI CTCAE Version 4.03

    The reported output is the proportion of patients that had a toxic event along with the associated 90% Wilson's confidence interval.

    Measured: Up to 2 years

  3. Overall Survival (Phase II)

    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.

    Measured: Up to 7 months post treatment initiation

Secondary outcomes (3)

  1. Effects the Study Drug Combination Has on Participants

    Pharmacodynamics of selinexor in combination with gemcitabine hydrochloride and paclitaxel albumin-stabilized nanoparticle formulation

    Measured: Day 1 of course 1 (before selinexor administration, 1, 2, 4 and 8 hours after selinexor administration) and days 2, 3 and 8

  2. Proportion of Patients With a Response

    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.

    Measured: Up to 2 years

  3. Progression Free Survival (Phase II)

    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.

    Measured: Up to 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted30 Jun 2014 (estimated)
  2. Study start31 Oct 2014
  3. Primary completion27 Nov 2021
  4. Study completion5 Apr 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
Phase I is completed, due to Dose Limiting Toxicities (DLT).
Masking
None (open label)
Enrolment
15 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02178436
Sponsor's protocol ID
2013-133
Other IDs
NCI-2014-01249
Status last verified
Nov 2023
First submitted
23 Jun 2014
Last updated
7 Nov 2023
Data monitoring committee
Yes

Publications

  • Azmi AS, Khan HY, Muqbil I, Aboukameel A, Neggers JE, Daelemans D, Mahipal A, Dyson G, Kamgar M, Al-Hallak MN, Tesfaye A, Kim S, Shidham V, M Mohammad R, Philip PA. Preclinical Assessment with Clinical Validation of Selinexor with Gemcitabine and Nab-Paclitaxel for the Treatment of Pancreatic Ductal Adenocarcinoma. Clin Cancer Res. 2020 Mar 15;26(6):1338-1348. doi: 10.1158/1078-0432.CCR-19-1728. Epub 2019 Dec 12.

    PubMed 31831564

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing gemcitabine hydrochloride, Selinexor and Pharmacological Study in people with Acinar Cell Adenocarcinoma of the Pancreas and Duct Cell Adenocarcinoma of the Pancreas, run by Mohammed Najeeb Al Hallak at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 7 Nov 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 7 Nov 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Maximum Tolerated Dose (MTD) of Selinexor, Gemcitabine Hydrochloride, and Paclitaxel Albumin-stabilized Nanoparticle Formulation Combination (Phase Ib) (time frame: 28 days). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02178436, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Nov 2023.

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