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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT02178436
Other study ID # 2013-133
Secondary ID NCI-2014-01249
Status Completed
Phase Phase 1/Phase 2
First received
Last updated
Start date October 31, 2014
Est. completion date April 5, 2023

Study information

Verified date November 2023
Source Barbara Ann Karmanos Cancer Institute
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical 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). 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.


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.


Recruitment information / eligibility

Status Completed
Enrollment 15
Est. completion date April 5, 2023
Est. primary completion date November 27, 2021
Accepts healthy volunteers No
Gender All
Age group 19 Years and older
Eligibility 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 Design


Related Conditions & MeSH terms


Intervention

Drug:
gemcitabine hydrochloride
Given IV
Selinexor
Given IV
Other:
Pharmacological Study
Correlative studies
Laboratory Biomarker Analysis
Correlative studies
Drug:
Nab paclitaxel
Given IV

Locations

Country Name City State
United States Barbara Ann Karmanos Cancer Institute Detroit Michigan
United States Stony Brook University Cancer Center Stony Brook New York

Sponsors (1)

Lead Sponsor Collaborator
Mohammed Najeeb Al Hallak

Country where clinical trial is conducted

United States, 

Outcome

Type Measure Description Time frame Safety issue
Other 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) 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
Primary 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
Primary 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
Primary 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 Effects the Study Drug Combination Has on Participants 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
Secondary 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. Up to 2 years
Secondary 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. Up to 2 years
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