Gemcitabine, Nab-paclitaxel and KPT-330 in Advanced Pancreatic Cancer
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
2 other identifiers
interventional
15
1 country
2
Brief 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). 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_1
Started Oct 2014
Longer than P75 for phase_1
2 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
June 23, 2014
CompletedFirst Posted
Study publicly available on registry
June 30, 2014
CompletedStudy Start
First participant enrolled
October 31, 2014
CompletedPrimary Completion
Last participant's last visit for primary outcome
November 27, 2021
CompletedStudy Completion
Last participant's last visit for all outcomes
April 5, 2023
CompletedResults Posted
Study results publicly available
November 7, 2023
CompletedNovember 7, 2023
November 1, 2023
7.1 years
June 23, 2014
September 13, 2023
November 5, 2023
Conditions
Outcome Measures
Primary Outcomes (3)
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.
28 days
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.
Up to 2 years
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.
Up to 7 months post treatment initiation
Secondary Outcomes (3)
Effects the Study Drug Combination Has on Participants
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
Up to 2 years
Progression Free Survival (Phase II)
Up to 2 years
Other Outcomes (1)
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)
Baseline to up to 2 years
Study Arms (3)
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.
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
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.
Interventions
Given IV
Given IV
Correlative studies
Correlative studies
Given IV
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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
- +5 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (2)
Barbara Ann Karmanos Cancer Institute
Detroit, Michigan, 48201, United States
Stony Brook University Cancer Center
Stony Brook, New York, 11794, United States
Related Publications (1)
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.
PMID: 31831564DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Mohammed Najeeb Al Hallak M.D.
- Organization
- Karmanos Cancer Institute
Study Officials
- PRINCIPAL INVESTIGATOR
Mohammed N Al Hallak, M.D.
Barbara Ann Karmanos Cancer Institute
Publication Agreements
- PI is Sponsor Employee
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR INVESTIGATOR
- PI Title
- Principal Investigator
Study Record Dates
First Submitted
June 23, 2014
First Posted
June 30, 2014
Study Start
October 31, 2014
Primary Completion
November 27, 2021
Study Completion
April 5, 2023
Last Updated
November 7, 2023
Results First Posted
November 7, 2023
Record last verified: 2023-11