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Trial record 1 of 1 for:    NCT02419495
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Phase IB of Selinexor in Combination With Standard Chemotherapy in Patients With Advanced Malignancies

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ClinicalTrials.gov Identifier: NCT02419495
Recruitment Status : Recruiting
First Posted : April 17, 2015
Last Update Posted : November 6, 2018
Sponsor:
Collaborator:
Karyopharm Therapeutics Inc
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Brief Summary:

Objectives:

Primary Objective To establish the safety and tolerability of Selinexor when given in combination with standard chemotherapy regimens.

Secondary Objectives To determine disease control and progression free survival of Selinexor administered with standard chemotherapy treatments.

Exploratory Objectives To determine the correlation of translational biomarkers To compare serial assessment of mutation status in biopsies obtained at baseline and progression after clinical response to combination therapy

As of Amendment Version 12.0, Arms A, D, E, F, G, H, I, and J were closed to additional patient accrual due to lack of efficacy or toxicity.


Condition or disease Intervention/treatment Phase
Advanced Cancers Drug: Selinexor Drug: Carboplatin Drug: Paclitaxel Drug: Eribulin Drug: Doxorubicin Drug: Cyclophosphamide Drug: Pemetrexed Drug: Topotecan Drug: Irinotecan Drug: 5-FU Drug: Capecitabine Drug: Oxaliplatin Drug: Olaparib Drug: Pembrolizumab Drug: Nivolumab Phase 1

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 588 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase IB Study to Evaluate the Safety of Selinexor (KPT-330) in Combination With Multiple Standard Chemotherapy Agents in Patients With Advanced Malignancies
Actual Study Start Date : June 26, 2015
Estimated Primary Completion Date : December 2019
Estimated Study Completion Date : December 2019

Arm Intervention/treatment
Experimental: Arm A: Selinexor + Carboplatin

Selinexor escalated in combination with a fixed dose of carboplatin to evaluate the safety, tolerability, and MTD in patients with advanced solid tumors. In the expansion phase, there will be at least one histology-independent cohort of up to 9 patients that will be enrolled at the previously established safe dose for additional safety and correlative studies to establish the recommended phase 2 dose (RP2D) for this combination.

Selinexor given orally once a week for 3 weeks or Days 1, 8, and 15 of each 21-day cycle, and Carboplatin given at the fixed dose of 6 area under curve (AUC) intravenously (IV) every 3 weeks for 6 cycles then Selinexor can be given as a single agent until disease progression.

Arm Closed.

Drug: Selinexor

Arm A, C, D, E, F, G, I Dose Escalation Phase Starting Dose: 60 mg given orally once a week for 3 weeks.

Arm B Dose Escalation Phase Starting Dose: 60 mg given orally twice a week for the first two weeks of each 3 week cycle.

Arm H Dose Escalation Phase Starting Dose: 40 mg given orally once a week for 4 weeks.

Arm J Dose Escalation Phase Starting Dose: 40 mg given orally once a week for 3 weeks.

Arm K Dose Escalation Phase Starting Dose: 40 mg given orally twice weekly for 4 weeks.

Arm L Dose Escalation Phase Starting Dose: 40 mg given orally twice weekly for 4 weeks.

All Arms Dose Expansion Phase Starting Dose: MTD from dose escalation phase.

Other Name: KPT-330

Drug: Carboplatin

Arm A: Carboplatin given by vein at fixed dose of 6 AUC on day 1 of each 21 day cycle for up to 6 cycles.

Arm E and Arm F: Carboplatin given intravenously at fixed dose of 4 AUC on day 1 of each 21 day cycle for 6 or up to 8 cycles dependent on cancer type.

Other Name: Paraplatin

Experimental: Arm B: Selinexor + Paclitaxel

Dose escalation phase, dose of Selinexor escalated in combination with fixed dose of paclitaxel to evaluate the safety, tolerability, and MTD in patients with advanced solid tumors. In expansion phase, there will be two tumor-specific cohorts of 25 patients each (ovarian carcinoma and metastatic breast cancer) enrolled at the previously established safe dose for additional safety and correlative studies to establish the RP2D for this combination.

Selinexor given orally twice a week for the first two weeks of each 3-week (21-day) cycle. Paclitaxel given intravenously at a fixed dose of 80 mg/m2 on Day 1 and Day 8 of every 21-day cycle (weekly for 2 weeks on and 1 week off) for up to 8 cycles then Selinexor can be given as a single agent until disease progression.

Drug: Selinexor

Arm A, C, D, E, F, G, I Dose Escalation Phase Starting Dose: 60 mg given orally once a week for 3 weeks.

Arm B Dose Escalation Phase Starting Dose: 60 mg given orally twice a week for the first two weeks of each 3 week cycle.

Arm H Dose Escalation Phase Starting Dose: 40 mg given orally once a week for 4 weeks.

Arm J Dose Escalation Phase Starting Dose: 40 mg given orally once a week for 3 weeks.

Arm K Dose Escalation Phase Starting Dose: 40 mg given orally twice weekly for 4 weeks.

Arm L Dose Escalation Phase Starting Dose: 40 mg given orally twice weekly for 4 weeks.

All Arms Dose Expansion Phase Starting Dose: MTD from dose escalation phase.

Other Name: KPT-330

Drug: Paclitaxel

Arm B: Paclitaxel given intravenously at a fixed dose of 80 mg/m2 on Day 1 and Day 8 of every 21-day cycle (weekly for 2 weeks on and 1 week off) for up to 8 cycles.

Arm E: Paclitaxel given at doses of 175 or 200 mg/m2 by vein every 3 weeks for up to 8 cycles dependent on cancer type.

Other Name: Taxol

Experimental: Arm C: Selinexor + Eribulin

In dose escalation phase, dose of Selinexor escalated in combination with a fixed dose of eribulin to evaluate the safety, tolerability, and MTD in patients with advanced solid tumors. In expansion phase, there will be at least one histology-independent cohort of up to 9 patients enrolled at the previously established safe dose for additional safety and correlative studies to establish the RP2D for this combination.

Selinexor given orally once a week for 3 weeks or Days 1, 8, and 15 of each 21-day cycle. Eribulin given intravenously at a fixed dose of 1.0 mg/m2 on Days 1 and 8 of every 21-day cycle for 6 cycles then Selinexor can be given as a single agent until disease progression.

Drug: Selinexor

Arm A, C, D, E, F, G, I Dose Escalation Phase Starting Dose: 60 mg given orally once a week for 3 weeks.

Arm B Dose Escalation Phase Starting Dose: 60 mg given orally twice a week for the first two weeks of each 3 week cycle.

Arm H Dose Escalation Phase Starting Dose: 40 mg given orally once a week for 4 weeks.

Arm J Dose Escalation Phase Starting Dose: 40 mg given orally once a week for 3 weeks.

Arm K Dose Escalation Phase Starting Dose: 40 mg given orally twice weekly for 4 weeks.

Arm L Dose Escalation Phase Starting Dose: 40 mg given orally twice weekly for 4 weeks.

All Arms Dose Expansion Phase Starting Dose: MTD from dose escalation phase.

Other Name: KPT-330

Drug: Eribulin
Arm C: Eribulin given intravenously at fixed dose of 1.0 mg/m2 on Days 1 and 8 of every 21-day cycle for 6 cycles.
Other Name: E7389

Experimental: Arm D: Selinexor + Doxorubicin + Cyclophosphamide

In dose escalation phase, dose of Selinexor escalated in combination with fixed dose of combination doxorubicin and cyclophosphamide to evaluate the safety, tolerability, and MTD in patients with advanced solid tumors. In expansion phase, there will be at least one histology-independent cohort of up to 9 patients enrolled at the previously established safe dose for additional safety and correlative studies to establish the RP2D for the combination.

Selinexor given orally once a week for 3 weeks or Days 1, 8, or 15 of each 21 day cycle. Doxorubicin given at fixed dose of 60 mg/m2 by vein and cyclophosphamide given at fixed dose of 600 mg/m2 by vein every 3 weeks for 6 cycles then Selinexor can be given as a single agent.

Arm Closed.

Drug: Selinexor

Arm A, C, D, E, F, G, I Dose Escalation Phase Starting Dose: 60 mg given orally once a week for 3 weeks.

Arm B Dose Escalation Phase Starting Dose: 60 mg given orally twice a week for the first two weeks of each 3 week cycle.

Arm H Dose Escalation Phase Starting Dose: 40 mg given orally once a week for 4 weeks.

Arm J Dose Escalation Phase Starting Dose: 40 mg given orally once a week for 3 weeks.

Arm K Dose Escalation Phase Starting Dose: 40 mg given orally twice weekly for 4 weeks.

Arm L Dose Escalation Phase Starting Dose: 40 mg given orally twice weekly for 4 weeks.

All Arms Dose Expansion Phase Starting Dose: MTD from dose escalation phase.

Other Name: KPT-330

Drug: Doxorubicin
Arm D: Doxorubicin given intravenously at fixed dose of 60 mg/m2 on Day 1 of each 21 day cycle for 6 cycles.
Other Names:
  • Doxorubicin Hydrochloride
  • Adriamycin PFS
  • Adriamycin RDF
  • Adriamycin
  • Rubex

Drug: Cyclophosphamide
Arm D: Cyclophosphamide given intravenously at fixed dose of 600 mg/m2 on Day 1 of each 21 day cycle for 6 cycles.
Other Names:
  • Cytoxan
  • Neosar

Experimental: Arm E: Selinexor + Carboplatin + Paclitaxel

Dose escalation phase Selinexor dose escalated with fixed dose of carboplatin and paclitaxel up to dose level 2 to evaluate safety, tolerability, and MTD in patients with advanced solid tumors. There will be an additional dose level 3 using fixed dose of carboplatin but escalating the paclitaxel. In expansion phase, there will be one tumor-specific cohort of 25 ovarian carcinoma patients and one tumor-specific cohort of 25 non-small cell lung cancer patients.

Selinexor given orally once a week for 3 weeks in a 21 day cycle. Carboplatin 5 AUC by vein and paclitaxel given at doses of 175 or 200 mg/m2 by vein every 3 weeks for 6 or up to 8 cycles dependent on cancer type. After completion of carboplatin and paclitaxel treatment, Selinexor can be given as a single agent until disease progression.

Drug: Selinexor

Arm A, C, D, E, F, G, I Dose Escalation Phase Starting Dose: 60 mg given orally once a week for 3 weeks.

Arm B Dose Escalation Phase Starting Dose: 60 mg given orally twice a week for the first two weeks of each 3 week cycle.

Arm H Dose Escalation Phase Starting Dose: 40 mg given orally once a week for 4 weeks.

Arm J Dose Escalation Phase Starting Dose: 40 mg given orally once a week for 3 weeks.

Arm K Dose Escalation Phase Starting Dose: 40 mg given orally twice weekly for 4 weeks.

Arm L Dose Escalation Phase Starting Dose: 40 mg given orally twice weekly for 4 weeks.

All Arms Dose Expansion Phase Starting Dose: MTD from dose escalation phase.

Other Name: KPT-330

Drug: Carboplatin

Arm A: Carboplatin given by vein at fixed dose of 6 AUC on day 1 of each 21 day cycle for up to 6 cycles.

Arm E and Arm F: Carboplatin given intravenously at fixed dose of 4 AUC on day 1 of each 21 day cycle for 6 or up to 8 cycles dependent on cancer type.

Other Name: Paraplatin

Drug: Paclitaxel

Arm B: Paclitaxel given intravenously at a fixed dose of 80 mg/m2 on Day 1 and Day 8 of every 21-day cycle (weekly for 2 weeks on and 1 week off) for up to 8 cycles.

Arm E: Paclitaxel given at doses of 175 or 200 mg/m2 by vein every 3 weeks for up to 8 cycles dependent on cancer type.

Other Name: Taxol

Experimental: Arm F: Selinexor + Carboplatin + Pemetrexed

Dose escalation phase Selinexor dose escalated with fixed dose of combination carboplatin and pemetrexed to evaluate safety, tolerability, and MTD in patients with advanced solid tumors. In expansion phase, there will be at least one histology-independent cohort of up to 9 patients enrolled at the previously established safe dose for additional safety and correlative studies to establish the RP2D for this combination.

Selinexor given orally once a week for 3 weeks in a 21 day cycle. Carboplatin 6 AUC by vein, and pemetrexed 500 mg/m2 by vein every 3 weeks for up to 6 cycles. After completion of carboplatin and pemetrexed treatment, pemetrexed and Selinexor or single agent Selinexor can be given as a combination maintenance therapy until disease progression. Participants with mesothelioma continue with pemetrexed and Selinexor treatment, participants with other histological malignancies continue with single agent Selinexor.

Arm Closed.

Drug: Selinexor

Arm A, C, D, E, F, G, I Dose Escalation Phase Starting Dose: 60 mg given orally once a week for 3 weeks.

Arm B Dose Escalation Phase Starting Dose: 60 mg given orally twice a week for the first two weeks of each 3 week cycle.

Arm H Dose Escalation Phase Starting Dose: 40 mg given orally once a week for 4 weeks.

Arm J Dose Escalation Phase Starting Dose: 40 mg given orally once a week for 3 weeks.

Arm K Dose Escalation Phase Starting Dose: 40 mg given orally twice weekly for 4 weeks.

Arm L Dose Escalation Phase Starting Dose: 40 mg given orally twice weekly for 4 weeks.

All Arms Dose Expansion Phase Starting Dose: MTD from dose escalation phase.

Other Name: KPT-330

Drug: Carboplatin

Arm A: Carboplatin given by vein at fixed dose of 6 AUC on day 1 of each 21 day cycle for up to 6 cycles.

Arm E and Arm F: Carboplatin given intravenously at fixed dose of 4 AUC on day 1 of each 21 day cycle for 6 or up to 8 cycles dependent on cancer type.

Other Name: Paraplatin

Drug: Pemetrexed
Arm F: Pemetrexed given at fixed dose of 500 mg/m2 by vein every 3 weeks for up to 6 cycles. After completion of carboplatin and pemetrexed treatment, pemetrexed can be given as a combination maintenance therapy until disease progression. Participants with mesothelioma continue with pemetrexed treatment.
Other Names:
  • LY231514
  • Alimta
  • MTA
  • Multitargeted Antifolate
  • NSC-698037

Experimental: Arm G: Selinexor + Topotecan

In dose escalation phase, dose of Selinexor escalated in combination with escalated dose of topotecan to evaluate the safety, tolerability, and MTD in patients with advanced solid tumors. In expansion phase, at least one tumor-specific cohort of up to 25 ovarian carcinoma patients enrolled at previously established safe dose for additional safety and correlative studies to establish the RP2D for the combination.

Selinexor given orally once a week for 3 weeks or Days 1, 8, and 15 of each 21-day cycle, and topotecan given at starting dose of 0.5 mg/m2 by vein daily for 5 days every 3 weeks (Days 1-5 of every 21-day cycle) for up to 8 cycles, then Selinexor given as a single agent until disease progression.

Arm Closed.

Drug: Selinexor

Arm A, C, D, E, F, G, I Dose Escalation Phase Starting Dose: 60 mg given orally once a week for 3 weeks.

Arm B Dose Escalation Phase Starting Dose: 60 mg given orally twice a week for the first two weeks of each 3 week cycle.

Arm H Dose Escalation Phase Starting Dose: 40 mg given orally once a week for 4 weeks.

Arm J Dose Escalation Phase Starting Dose: 40 mg given orally once a week for 3 weeks.

Arm K Dose Escalation Phase Starting Dose: 40 mg given orally twice weekly for 4 weeks.

Arm L Dose Escalation Phase Starting Dose: 40 mg given orally twice weekly for 4 weeks.

All Arms Dose Expansion Phase Starting Dose: MTD from dose escalation phase.

Other Name: KPT-330

Drug: Topotecan
Arm G starting dose of Topotecan 0.5 mg/m2 given intravenously on days 1 - 5 of each 21 day cycle for 8 cycles.
Other Name: Hycamtin

Experimental: Arm H: Selinexor + FOLFIRI

In dose escalation phase, dose of Selinexor escalated in combination with a fixed dose of FOLFIRI (irinotecan and 5-FU) to evaluate the safety, tolerability, and MTD in patients with advanced solid tumors. In expansion phase, at least one tumor-specific cohort of up to 25 colorectal carcinoma patients enrolled at previously established safe dose for additional safety and correlative studies to establish the RP2D for this combination.

Selinexor given orally once a week for 4 weeks or Days 1, 8, 15, and 22 of each 28-day cycle, and the FOLFIRI regimen given at the fixed dose every 2 weeks or Days 1 and 15 of each 28-day cycle for 6 cycles (12 doses of FOLFIRI) then Selinexor given as a single agent until disease progression.

Arm Closed.

Drug: Selinexor

Arm A, C, D, E, F, G, I Dose Escalation Phase Starting Dose: 60 mg given orally once a week for 3 weeks.

Arm B Dose Escalation Phase Starting Dose: 60 mg given orally twice a week for the first two weeks of each 3 week cycle.

Arm H Dose Escalation Phase Starting Dose: 40 mg given orally once a week for 4 weeks.

Arm J Dose Escalation Phase Starting Dose: 40 mg given orally once a week for 3 weeks.

Arm K Dose Escalation Phase Starting Dose: 40 mg given orally twice weekly for 4 weeks.

Arm L Dose Escalation Phase Starting Dose: 40 mg given orally twice weekly for 4 weeks.

All Arms Dose Expansion Phase Starting Dose: MTD from dose escalation phase.

Other Name: KPT-330

Drug: Irinotecan

Arm H: Irinotecan 180 mg/m2 by vein every 2 weeks or Days 1 and 15 of each 28-day cycle for 6 cycles.

Arm I: Irinotecan 125 mg/m2 by vein on Days 1 and 8 of each 21-day cycle (2 weeks on and 1 week off) for 8 cycles.

Other Names:
  • CPT-11
  • Camptosar

Drug: 5-FU
Arm H: 5-FU 2400 mg/m2 (continuous by vein over 48 hours) and 5-FU 400 mg/m2 bolus every 2 weeks or Days 1 and 15 of each 28-day cycle for 6 cycles.
Other Names:
  • Fluorouracil
  • 5-Fluorouracil
  • Adrucil
  • Efudex

Experimental: Arm I: Selinexor + Irinotecan

In dose escalation phase, dose of Selinexor escalated in combination with fixed dose of irinotecan to evaluate the safety, tolerability, and MTD in patients with advanced solid tumors. In expansion phase, at least one tumor-specific cohort of up to 25 colorectal carcinoma patients enrolled at the previously established safe dose for additional safety and correlative studies to establish the RP2D for this combination.

Selinexor given orally once a week for 3 weeks or Days 1, 8, and 15 of each 21-day cycle, and irinotecan given at fixed dose of 125 mg/m2 by vein on Days 1 and 8 of each 21-day cycle (2 weeks on and 1 week off) for 8 cycles then Selinexor can be given as a single agent until disease progression.

Arm Closed.

Drug: Selinexor

Arm A, C, D, E, F, G, I Dose Escalation Phase Starting Dose: 60 mg given orally once a week for 3 weeks.

Arm B Dose Escalation Phase Starting Dose: 60 mg given orally twice a week for the first two weeks of each 3 week cycle.

Arm H Dose Escalation Phase Starting Dose: 40 mg given orally once a week for 4 weeks.

Arm J Dose Escalation Phase Starting Dose: 40 mg given orally once a week for 3 weeks.

Arm K Dose Escalation Phase Starting Dose: 40 mg given orally twice weekly for 4 weeks.

Arm L Dose Escalation Phase Starting Dose: 40 mg given orally twice weekly for 4 weeks.

All Arms Dose Expansion Phase Starting Dose: MTD from dose escalation phase.

Other Name: KPT-330

Drug: Irinotecan

Arm H: Irinotecan 180 mg/m2 by vein every 2 weeks or Days 1 and 15 of each 28-day cycle for 6 cycles.

Arm I: Irinotecan 125 mg/m2 by vein on Days 1 and 8 of each 21-day cycle (2 weeks on and 1 week off) for 8 cycles.

Other Names:
  • CPT-11
  • Camptosar

Experimental: Arm J: Selinexor + XELOX

In dose escalation phase, dose of Selinexor escalated in combination with a fixed dose of XELOX (capecitabine and oxaliplatin) to evaluate the safety, tolerability, and MTD in patients with advanced solid tumors. In expansion phase, at least one tumor-specific cohort of up to 25 colorectal carcinoma patients enrolled at the previously established safe dose for additional safety and correlative studies to establish the RP2D for this combination.

Selinexor given orally once a week for 3 weeks or Days 1, 8, and 15 of each 21-day cycle. Capecitabine given at fixed dose of 900 mg/m2 orally twice daily for Days 1-14 of each cycle, and oxaliplatin given at the fixed dose of 130 mg/m2 by vein every 3 weeks for 8 cycles then Selinexor can be given as a single agent until disease progression.

Arm Closed.

Drug: Selinexor

Arm A, C, D, E, F, G, I Dose Escalation Phase Starting Dose: 60 mg given orally once a week for 3 weeks.

Arm B Dose Escalation Phase Starting Dose: 60 mg given orally twice a week for the first two weeks of each 3 week cycle.

Arm H Dose Escalation Phase Starting Dose: 40 mg given orally once a week for 4 weeks.

Arm J Dose Escalation Phase Starting Dose: 40 mg given orally once a week for 3 weeks.

Arm K Dose Escalation Phase Starting Dose: 40 mg given orally twice weekly for 4 weeks.

Arm L Dose Escalation Phase Starting Dose: 40 mg given orally twice weekly for 4 weeks.

All Arms Dose Expansion Phase Starting Dose: MTD from dose escalation phase.

Other Name: KPT-330

Drug: Capecitabine
Arm J: Capecitabine 900 mg/m2 taken orally twice daily for Days 1-14 of each cycle for 8 cycles.
Other Name: Xeloda

Drug: Oxaliplatin
Arm J: Oxaliplatin 130 mg/m2 by vein every 3 weeks for 8 cycles.
Other Name: Eloxatin

Experimental: Arm K: Selinexor + Olaparib

In dose escalation phase, dose of Selinexor escalated in combination with fixed dose of olaparib to evaluate the safety, tolerability, and MTD in patients with advanced solid tumors. In expansion phase, at least one tumor-specific cohort of up to 25 ovarian carcinoma patients enrolled at the previously established safe dose for additional safety and correlative studies to establish the RP2D for this combination.

Selinexor given orally twice weekly (e.g. Monday/ Wednesday or Tuesday/Thursday or Wednesday/Friday or Thursday/Saturday or Friday/Sunday) for 4 weeks of each 28-day cycle, and olaparib given at fixed dose of 400 mg/m2 taken orally twice daily continuously for as many cycles at the discretion of the attending physician, then Selinexor can be given as a single agent until disease progression.

Drug: Selinexor

Arm A, C, D, E, F, G, I Dose Escalation Phase Starting Dose: 60 mg given orally once a week for 3 weeks.

Arm B Dose Escalation Phase Starting Dose: 60 mg given orally twice a week for the first two weeks of each 3 week cycle.

Arm H Dose Escalation Phase Starting Dose: 40 mg given orally once a week for 4 weeks.

Arm J Dose Escalation Phase Starting Dose: 40 mg given orally once a week for 3 weeks.

Arm K Dose Escalation Phase Starting Dose: 40 mg given orally twice weekly for 4 weeks.

Arm L Dose Escalation Phase Starting Dose: 40 mg given orally twice weekly for 4 weeks.

All Arms Dose Expansion Phase Starting Dose: MTD from dose escalation phase.

Other Name: KPT-330

Drug: Olaparib
Arm K: Olaparib 400 mg/m2 taken orally twice daily continuously for as many cycles at the discretion of the attending physician.
Other Name: Lynparza

Experimental: Arm L: Selinexor + Pembrolizumab

In dose escalation phase, dose of Selinexor escalated in combination with a fixed dose of pembrolizumab to evaluate the safety, tolerability, and MTD in patients with advanced solid tumors. In expansion phase, at least one tumor-specific cohort of up to 25 melanoma patients and up to 25 NSCLC patients enrolled at the previously established safe dose for additional safety and correlative studies to establish the RP2D for this combination.

Selinexor given twice weekly (e.g. Monday/ Wednesday or Tuesday/Thursday or Wednesday/Friday or Thursday/Saturday or Friday/Sunday) for 3 weeks of each 21-day cycle, and pembrolizumab given at fixed dose of 2 mg/kg by vein every 3 weeks for as many cycles at the discretion of the attending physician, then Selinexor can be given as a single agent until disease progression.

Drug: Selinexor

Arm A, C, D, E, F, G, I Dose Escalation Phase Starting Dose: 60 mg given orally once a week for 3 weeks.

Arm B Dose Escalation Phase Starting Dose: 60 mg given orally twice a week for the first two weeks of each 3 week cycle.

Arm H Dose Escalation Phase Starting Dose: 40 mg given orally once a week for 4 weeks.

Arm J Dose Escalation Phase Starting Dose: 40 mg given orally once a week for 3 weeks.

Arm K Dose Escalation Phase Starting Dose: 40 mg given orally twice weekly for 4 weeks.

Arm L Dose Escalation Phase Starting Dose: 40 mg given orally twice weekly for 4 weeks.

All Arms Dose Expansion Phase Starting Dose: MTD from dose escalation phase.

Other Name: KPT-330

Drug: Pembrolizumab
Arm L: Pembrolizumab given at the fixed dose of 2 mg/kg by vein every 3 weeks for as many cycles at the discretion of the attending physician.
Other Names:
  • Keytruda
  • MK-3475
  • SCH-900475

Experimental: Arm M: Selinexor + Nivolumab

In dose escalation phase, dose of Selinexor escalated in combination with with a fixed dose of Nivolumab.

Selinexor 40 mg taken orally twice weekly, either on Monday and Wednesday or on Tuesday and Thursday or on Wednesday and Friday or Thursday/Saturday or Friday/Sunday, for 4 weeks. One cycle is defined as 28 days or 8 doses.

Nivolumab 240 mg by vein every 2 weeks or Days 1 and 15 of each 28-day cycle.

Drug: Selinexor

Arm A, C, D, E, F, G, I Dose Escalation Phase Starting Dose: 60 mg given orally once a week for 3 weeks.

Arm B Dose Escalation Phase Starting Dose: 60 mg given orally twice a week for the first two weeks of each 3 week cycle.

Arm H Dose Escalation Phase Starting Dose: 40 mg given orally once a week for 4 weeks.

Arm J Dose Escalation Phase Starting Dose: 40 mg given orally once a week for 3 weeks.

Arm K Dose Escalation Phase Starting Dose: 40 mg given orally twice weekly for 4 weeks.

Arm L Dose Escalation Phase Starting Dose: 40 mg given orally twice weekly for 4 weeks.

All Arms Dose Expansion Phase Starting Dose: MTD from dose escalation phase.

Other Name: KPT-330

Drug: Nivolumab
Arm M: Nivolumab 240 mg by vein every 2 weeks or Days 1 and 15 of each 28-day cycle.
Other Names:
  • BMS-936558
  • Opdivo




Primary Outcome Measures :
  1. Maximum Tolerated Dose (MTD) [ Time Frame: 21 or 28 days depending on the arm assignment ]
    MTD defined as the highest dose level with an observed incidence of dose limiting toxicity (DLT) in ≤ 33% of patients enrolled in a dose escalation cohort.


Secondary Outcome Measures :
  1. Disease Control [ Time Frame: 6 months ]
    Disease control defined as complete response, partial response + stable disease for at least 6 months, measured by objective tumor response according to RECIST 1.1 criteria.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patients must have histologically or cytologically confirmed malignant neoplasms (not including hematological malignancies and brain tumors) untreated or previously treated requiring further treatment. Patients must be refractory to, intolerant of, established therapy known to provide clinical benefit for their condition. Patients in Arm L (Pembrolizumab) and Arm M (Nivolumab) can be treatment naïve and do not have to fail first line nivolumab or pembrolizumab if they have disease where pembrolizumab or nivolumab are FDA approved for the first-line setting.
  2. For all arms except Arm L (Pembrolizumab) and Arm M (Nivolumab), patients must have failed prior standard curative chemotherapy for their disease. Subjects must have failed, be intolerant to, or be ineligible for any potentially curative approved treatment, irrespective of line of therapy.
  3. Patients must have either measurable disease (RECIST 1.1) or evaluable disease (non-measurable lesions) outside irradiated field on CT/MRI.
  4. Age >/= 18 years.
  5. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
  6. The patient must be recovered from a prior major surgery. The major surgery must be performed at least 4 weeks prior to consent date.
  7. Adequate hematologic function defined as: platelets >/= 125 x 10^9/L (For Arm L Pembrolizumab and Arm M Nivolumab and Expansion cohorts for all arms, platelets >/= 100 x 10^9/L); hemoglobin >/= 10 g/dL (For Arm L Pembrolizumab and Arm M Nivolumab and Expansion cohorts for all arms, hemoglobin >/= 9 g/dL); ANC >/= 1.5 x 10^9/L; WBC >/= 3 x 109/L. Transfusions and growth factors are allowed.
  8. Adequate liver function defined as: Alanine transaminase (ALT) </= 2 x upper normal limit (ULN) (In the expansion cohort, patients with known liver involvement may have ALT </= 5 x ULN); Aspartate aminotransferase (AST) </= 2 x ULN (In the expansion cohort, patients with known liver involvement may have AST </= 5 x ULN); Alkaline phosphatase < 4 x ULN; Total Bilirubin </= 2 x ULN (In the expansion cohort, patients with Gilbert's syndrome [hereditary indirect hyperbilirubinemia] who must have a total bilirubin of </= 3 x ULN); Albumin >/= 3 g/dL.
  9. Renal function defined as a calculated or measured glomerular filtration rate (GFR) >/=30 mL/min.
  10. The patient has recovered to Grade </= 1 by the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.03 (NCI-CTCAE v4.03) from the effects of recent surgery, radiotherapy, chemotherapy, hormonal therapy, or other targeted therapies, with the exception of alopecia. The exceptions for such effects are allowed lab values of </= Grade 2 specified elsewhere in these inclusion criteria.
  11. Life expectancy of at least 12 weeks.
  12. Able to swallow and retain oral medication.
  13. Patients must give informed consent according to the rules and regulations of the individual participating sites.
  14. Negative serum pregnancy test in women of childbearing potential within 7 days of first dose of treatment and patients of child-bearing potential must agree to use effective contraception during/after 3 months post dose. A woman of childbearing potential is defined as a premenopausal female capable of becoming pregnant. This includes women on oral, injectable or mechanical contraception; women who are single and women whose male sexual partners have been vasectomized or whose male sexual partners have received or are utilizing mechanical contraceptive devices.
  15. For the Arm B (Paclitaxel) expansion cohort, patients must have ovarian carcinoma.
  16. For Arm C (Eribulin) expansion cohort, patients must have triple negative breast cancer (eribulin naïve).
  17. For Arm K (Olaparib), patients must have pre-identified BRCA + ovarian or breast cancer.

Exclusion Criteria:

  1. Evidence of complete or partial bowel obstruction.
  2. Patients with primary CNS tumor or CNS tumor involvement. However, patients with metastatic CNS tumors may participate in this study if the patient is: > 4 weeks from prior therapy completion (including radiation and/or surgery); Clinically stable with respect to the CNS tumor at the time of study entry; Not receiving steroid therapy in treating CNS tumor or CNS tumor involvement; Not receiving anti-convulsive medications (that were started for brain metastases).
  3. Need of Total Parenteral Nutrition.
  4. Prior treatment with an agent targeting the Exportin.
  5. Allergic to Selinexor or any of the chemotherapy intended to receive.
  6. Pregnancy or lactation.
  7. Radiation (except planned or ongoing palliative radiation to bone outside of the region of measurable disease) </= 3 weeks prior to study drug administration date.
  8. Chemotherapy, or immunotherapy or any other systemic anticancer therapy </=3 weeks prior to study drug administration date. Patients receiving anti-PD-1 treatment, and continue to receiving this treatment in combination with Selinexor (Arms L and M), can start receiving the Selinexor and Anti-PD-1 combination without washout of the prior anti-PD-1 antibody.
  9. Diagnosis or recurrence of invasive cancer other than the present cancer within 3 years (except basal or squamous cell carcinoma of the skin that has been definitively treated).
  10. Major surgery within four weeks before consent date.
  11. Unstable cardiovascular function: Symptomatic ischemia (chest pain of cardiac origin), or Uncontrolled clinically significant conduction abnormalities (e.g. ventricular tachycardia on antiarrhythmics are excluded and 1st degree AV block or asymptomatic LAFB/ RBBB will not be excluded), or Congestive heart failure (CHF) of NYHA Class >/= 3, or Myocardial infarction (MI) within 3 months of consent date.
  12. Uncontrolled active infection requiring parenteral antibiotics, antivirals, or antifungals within one week prior to the first dose. Active infection with concurrent treatment is acceptable only if the patient is clinically stable.
  13. Significantly diseased (as determined by the PI or treating physician) or obstructed gastrointestinal tract or uncontrolled vomiting or diarrhea.
  14. Treatment with an investigational anti-cancer study drug within 3 weeks prior to study drug administration date.
  15. Concurrent therapy with approved or investigational anticancer therapeutics.
  16. Medical, psychological or social conditions that may interfere with the patient's participation in the study or evaluation of the study results
  17. Men whose partner is a woman of child-bearing potential, (i.e. biologically able to conceive), and who is not employing two forms of highly effective contraception. Highly effective contraception (e.g. male condom with spermicide, diaphragm with spermicide, intra-uterine device) must be used by both sexes during the study and must be continued for 3 months after the end of study treatment. Women of child-bearing potential is defined as sexually mature women who are not surgically sterile or who have not been naturally postmenopausal for at least 12 consecutive months (e.g., who has had menses any time in the preceding 12 consecutive months).
  18. For Arms L (Pembrolizumab) and M (Nivolumab), subjects with an active, known or suspected autoimmune disease. Subjects with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
  19. For Arms L (Pembrolizumab) and M (Nivolumab), subjects receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or other form of immunosuppressive therapy within 7 days before the first dose of study treatment. Use of inhaled or topical steroids or systemic corticosteroids </= 10 mg is permitted.
  20. For Arms L (Pembrolizumab) and M (Nivolumab), history of a prior Grade 3 or 4 immune-related adverse event (irAE) or any grade ocular irAE from prior immunotherapy.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02419495


Contacts
Contact: Aung Naing, MD 713-563-1930

Locations
United States, Texas
University of Texas MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Karyopharm Therapeutics Inc
Investigators
Principal Investigator: Aung Naing, MD M.D. Anderson Cancer Center

Additional Information:
Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT02419495     History of Changes
Other Study ID Numbers: 2014-0640
NCI-2015-00693 ( Registry Identifier: NCI CTRP )
First Posted: April 17, 2015    Key Record Dates
Last Update Posted: November 6, 2018
Last Verified: November 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by M.D. Anderson Cancer Center:
Advanced cancers
Malignant neoplasms
Paclitaxel
Taxol
Eribulin
E7389
Doxorubicin
Doxorubicin Hydrochloride
Adriamycin PFS
Adriamycin RDF
Adriamycin
Rubex
Cyclophosphamide
Cytoxan
Neosar
Pemetrexed
LY231514
Alimta
MTA
Multitargeted Antifolate
NSC-698037
Topotecan
Hycamtin
Selinexor
KPT-330
Carboplatin
Paraplatin
Irinotecan
CPT-11
Camptosar

Additional relevant MeSH terms:
Paclitaxel
Irinotecan
Camptothecin
Oxaliplatin
Liposomal doxorubicin
Pembrolizumab
Nivolumab
Olaparib
Albumin-Bound Paclitaxel
Cyclophosphamide
Carboplatin
Capecitabine
Doxorubicin
Fluorouracil
Pemetrexed
Topotecan
Antibodies, Monoclonal
Folic Acid Antagonists
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents