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

Brief summary public domain (ClinicalTrials.gov)

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.

Detailed description public domain (ClinicalTrials.gov)

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.

Posted results (ClinicalTrials.gov registry) · primary outcome public domain (ClinicalTrials.gov)

Maximum Tolerated Dose (MTD) of Selinexor, Gemcitabine Hydrochloride, and Paclitaxel Albumin-stabilized Nanoparticle Formulation Combination (Phase Ib) [28 days]. Number, milligrams. Group I: Phase Ib (Gemcitabine, Nab-paclitaxel, Selinexor) (n=9): 80.

Posted results (ClinicalTrials.gov registry) · primary outcome public domain (ClinicalTrials.gov)

Proportion of Patients With a Toxic Event, Graded According to NCI CTCAE Version 4.03 [Up to 2 years]. Number, proportion of patients (90% Confidence Interval). Group I: Phase Ib (Gemcitabine, Nab-paclitaxel, Selinexor) (n=9): 1.00 (0.77 to 1.00); GroupIII: Phase II Group II (Gemcitabine, Selinexor) (n=4): 0.75 (0.36 to 0.94).

Posted results (ClinicalTrials.gov registry) · primary outcome public domain (ClinicalTrials.gov)

Overall Survival (Phase II) [Up to 7 months post treatment initiation]. Median, months (90% Confidence Interval). Group I: Phase Ib (Gemcitabine, Nab-paclitaxel, Selinexor) (n=9): 5.45 (4.37 to NA) [Median survival (MS) is calculated by using the Kaplan-Meier (KM) curve. The MS is found by seeing where the estimated KM curve intersects with the horizontal line indicating 50% survival (HL-50). The upper 90% confidence value for the MS is found by seeing where the upper confidence band (CB) for the KM estimate intersects with HL-50. For this analysis, the upper CB does not cross 0.5 for the whole time period under study; so it never intersects with HL-50; and thus is not available to report]; GroupIII: Phase II Group II (Gemcitabine, Selinexor) (n=4): NA (NA to NA) [No survival events occurred in this group during the follow-up time. Therefore a median survival and confidence interval are not estimable.].

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

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].

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Proportion of Patients With a Response [Up to 2 years]. Number, proportion of patients (90% Confidence Interval). Group I: Phase Ib (Gemcitabine, Nab-paclitaxel, Selinexor) (n=5): 0.40 (0.14 to 0.73); GroupIII: Phase II Group II (Gemcitabine, Selinexor) (n=4): 0 (0 to 0.40).

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Progression Free Survival (Phase II) [Up to 2 years]. Median, months (90% Confidence Interval). Group I: Phase Ib (Gemcitabine, Nab-paclitaxel, Selinexor) (n=9): 4.60 (4.37 to NA) [Median survival (MS) is calculated by using the Kaplan-Meier (KM) curve. The MS is found by seeing where the estimated KM curve intersects with the horizontal line indicating 50% survival (HL-50). The upper 90% confidence value for the MS is found by seeing where the upper confidence band (CB) for the KM estimate intersects with HL-50. For this analysis, the upper CB does not cross 0.5 for the whole time period under study; so it never intersects with HL-50; and thus is not available to report]; GroupIII: Phase II Group II (Gemcitabine, Selinexor) (n=4): 1.74 (1.22 to NA) [Median survival (MS) is calculated by using the Kaplan-Meier (KM) curve. The MS is found by seeing where the estimated KM curve intersects with the horizontal line indicating 50% survival (HL-50). The upper 90% confidence value for the MS is found by seeing where the upper confidence band (CB) for the KM estimate intersects with HL-50. For this analysis, the upper CB does not cross 0.5 for the whole time period under study; so it never intersects with HL-50; and thus is not available to report].