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A Phase I Trial to Assess the Effects of Food and Formulation on PK of KPT-330 in Patients With Sarcoma

Primary Purpose

Sarcoma

Status

Completed

Phase

Phase 1

Locations

International

Study Type

Interventional

Intervention

KCP-330

About this trial

This is an interventional treatment trial for Sarcoma focused on measuring bone, soft-tissue, sarcoma, KPT-330, food, effects, Selinexor

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Patients must have histologically confirmed soft tissue or bone/cartilage sarcoma. Patients with sarcoma of small round blue cell tumor types are allowed. Gastrointestinal stromal tumors (GIST) are excluded.
Patients must have received at least one prior anticancer regimen for metastatic disease unless there is no other therapy available and evidence of progressive disease on study entry. Patients with stable disease will be included if there has been failure to respond to another drug(s) within the previous 3 months

Exclusion Criteria:

Patients with known liver metastases
Radiation, chemotherapy, immunotherapy, any other systemic anticancer therapy or participation in an investigational anti-cancer study ≤ 3 weeks prior to initiation of therapy
Patients with known brain metastasis
Patients with any gastrointestinal dysfunctions that could interfere with the interpretation of the food effect data
Patients with known intolerance to low or high fat meals
In the opinion of the investigator, patients who are significantly below their ideal body weight

Sites / Locations

Memorial Sloan Kettering Cancer Centre
Princess Margaret Hospital

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm Type

Experimental

Arm Label

Arm 1 - Treatment A, B, C, D

Arm 2 - Treatment B, A, D, C

Arm 3

Arm 4 - Treatment A, B, C

Arm 5 - Treatment C, A, B

Arm 6 - Treatment B, C, A

Arm Description

There are 4 treatment formulations of KCP-330: A: fasted, tablet formulation B: high-fat meal, tablet formulation C: low-fat meal, tablet formulation D: low-fat meal, capsule formulation In Arm 1, the following order will be utilized: Week 1, day 1: Treatment A Week 2, day 1: Treatment B Week 3, day 1: Treatment C Week 4, day 1: Treatment D (Note that recruitment has been completed for this arm)

There are 4 treatment formulations of KCP-330: A: fasted, tablet formulation B: high-fat meal, tablet formulation C: low-fat meal, tablet formulation D: low-fat meal, capsule formulation In Arm 2, the following order will be utilized: Week 1, day 1: Treatment B Week 2, day 1: Treatment A Week 3, day 1: Treatment D Week 4, day 1: Treatment C (Note that recruitment has been completed for this arm)

To evaluate tumor response in sarcoma patients (RECIST v1.1 criteria) on KCP-330. (Note that recruitment has been completed for this arm)

There are 3 treatment formulations of KCP-330: A: Current (1st generation) tablets, 60 mg B: New (2nd generation) tablets, 60 mg C: Suspension dose of current (1st generation) tablets, 60 mg In Arm 4, the following order will be utilized: Week 1, day 1: Treatment A Week 2, day 1: Treatment B Week 3, day 1: Treatment C

There are 3 treatment formulations of KCP-330: A: Current (1st generation) tablets, 60 mg B: New (2nd generation) tablets, 60 mg C: Suspension dose of current (1st generation) tablets, 60 mg In Arm 5, the following order will be utilized: Week 1, day 1: Treatment C Week 2, day 1: Treatment A Week 3, day 1: Treatment B

There are 3 treatment formulations of KCP-330: A: Current (1st generation) tablets, 60 mg B: New (2nd generation) tablets, 60 mg C: Suspension dose of current (1st generation) tablets, 60 mg In Arm 6, the following order will be utilized: Week 1, day 1: Treatment B Week 2, day 1: Treatment C Week 3, day 1: Treatment A

Outcomes

Primary Outcome Measures

Area under the plasma concentration versus time curve (AUC) of KPT-330

Secondary Outcome Measures

Tumor response in sarcoma patients (RECISTv1.1 criteria)

Change in laboratory parameters (serum chemistry, hematology and urinalysis)

Change in ECG parameters

Change in Vital sign parameters (Systolic pressure, diastolic pressure and heart rate)

Number and percentages of patients involved per CTCAE Category and CTCAE Term

Highest relation of an AE to study drug

Maximum AE severity

Full Information

NCT ID

NCT01896505

First Posted

June 11, 2013

Last Updated

August 28, 2018

Sponsor

Karyopharm Therapeutics Inc

1. Study Identification

Unique Protocol Identification Number

NCT01896505

Brief Title

A Phase I Trial to Assess the Effects of Food and Formulation on PK of KPT-330 in Patients With Sarcoma

Official Title

An Open-Label Phase IB Trial To Evaluate the Effects of Food and Formulation on Pharmacokinetics of the Oral Selective Inhibitor of Nuclear Export/SINE Compound KPT-330 in Patients With Soft-Tissue or Bone Sarcoma

Study Type

Interventional

2. Study Status

Record Verification Date

August 2018

Overall Recruitment Status

Completed

Study Start Date

July 2013 (undefined)

Primary Completion Date

November 2016 (Actual)

Study Completion Date

November 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Karyopharm Therapeutics Inc

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

The purpose of this research study is to find out more information such as: to determine the effects of high and low fat foods on the pharmacokinetics (PK) of oral KPT-330 tablets, to compare PK of capsules and tablets, to assess the effects of KPT-330 on cellular morphology and biomarker changes on sarcoma biopsy specimens (in patients who can safely undergo biopsy).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Sarcoma

Keywords

bone, soft-tissue, sarcoma, KPT-330, food, effects, Selinexor

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

54 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Arm 1 - Treatment A, B, C, D

Arm Type

Experimental

Arm Description

Arm Title

Arm 2 - Treatment B, A, D, C

Arm Type

Experimental

Arm Description

There are 4 treatment formulations of KCP-330: A: fasted, tablet formulation B: high-fat meal, tablet formulation C: low-fat meal, tablet formulation D: low-fat meal, capsule formulation In Arm 2, the following order will be utilized: Week 1, day 1: Treatment B Week 2, day 1: Treatment A Week 3, day 1: Treatment D Week 4, day 1: Treatment C (Note that recruitment has been completed for this arm)

Arm Title

Arm 3

Arm Type

Experimental

Arm Description

To evaluate tumor response in sarcoma patients (RECIST v1.1 criteria) on KCP-330. (Note that recruitment has been completed for this arm)

Arm Title

Arm 4 - Treatment A, B, C

Arm Type

Experimental

Arm Description

Arm Title

Arm 5 - Treatment C, A, B

Arm Type

Experimental

Arm Description

There are 3 treatment formulations of KCP-330: A: Current (1st generation) tablets, 60 mg B: New (2nd generation) tablets, 60 mg C: Suspension dose of current (1st generation) tablets, 60 mg In Arm 5, the following order will be utilized: Week 1, day 1: Treatment C Week 2, day 1: Treatment A Week 3, day 1: Treatment B

Arm Title

Arm 6 - Treatment B, C, A

Arm Type

Experimental

Arm Description

There are 3 treatment formulations of KCP-330: A: Current (1st generation) tablets, 60 mg B: New (2nd generation) tablets, 60 mg C: Suspension dose of current (1st generation) tablets, 60 mg In Arm 6, the following order will be utilized: Week 1, day 1: Treatment B Week 2, day 1: Treatment C Week 3, day 1: Treatment A

Intervention Type

Drug

Intervention Name(s)

KCP-330

Other Intervention Name(s)

Selinexor

Primary Outcome Measure Information:

Title

Area under the plasma concentration versus time curve (AUC) of KPT-330

Time Frame

At baseline (time 0) and on Day 1 of weeks 1 - 4 in Cycle 1 at the following timepoints:15 min, 30 min, 1, 1.5, 2, 3, 4, 5, 6, 8, 10,18 and 24 hours post dose

Secondary Outcome Measure Information:

Title

Tumor response in sarcoma patients (RECISTv1.1 criteria)

Time Frame

CT scans will be done at 8 weeks post dose and every 2 months while on study drug; and 30 days after the last dose in the study.

Title

Change in laboratory parameters (serum chemistry, hematology and urinalysis)

Time Frame

Baseline and Day 1 of weeks 1 -4 in Cycle 1

Title

Change in ECG parameters

Time Frame

Baseline and Day 1 of each week (weeks 1-4) in Cycle 1

Title

Change in Vital sign parameters (Systolic pressure, diastolic pressure and heart rate)

Time Frame

Baseline and on Day 1 of each week (weeks 1 - 4) of Cycle 1

Title

Number and percentages of patients involved per CTCAE Category and CTCAE Term

Time Frame

After first dose of drug until final study visit

Title

Highest relation of an AE to study drug

Time Frame

After first dose until final visit

Title

Maximum AE severity

Time Frame

After first dose of study drug until the final study visit

Other Pre-specified Outcome Measures:

Title

Biomarker changes on sarcoma biopsy specimens (in patients who can safely undergo biopsy).

Time Frame

Baseline and Week 3 or 4 of Cycle 1

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Patients must have histologically confirmed soft tissue or bone/cartilage sarcoma. Patients with sarcoma of small round blue cell tumor types are allowed. Gastrointestinal stromal tumors (GIST) are excluded. Patients must have received at least one prior anticancer regimen for metastatic disease unless there is no other therapy available and evidence of progressive disease on study entry. Patients with stable disease will be included if there has been failure to respond to another drug(s) within the previous 3 months Exclusion Criteria: Patients with known liver metastases Radiation, chemotherapy, immunotherapy, any other systemic anticancer therapy or participation in an investigational anti-cancer study ≤ 3 weeks prior to initiation of therapy Patients with known brain metastasis Patients with any gastrointestinal dysfunctions that could interfere with the interpretation of the food effect data Patients with known intolerance to low or high fat meals In the opinion of the investigator, patients who are significantly below their ideal body weight

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Michael Kauffman, MD, Ph.D

Organizational Affiliation

Karyopharm Therapeutics Inc

Official's Role

Study Director

Facility Information:

Facility Name

Memorial Sloan Kettering Cancer Centre

City

New York

State/Province

New York

ZIP/Postal Code

10065

Country

United States

Facility Name

Princess Margaret Hospital

City

Toronto

State/Province

Ontario

ZIP/Postal Code

M5T 2M9

Country

Canada

12. IPD Sharing Statement

Plan to Share IPD

Yes

Citations:

PubMed Identifier

27458288

Citation

Gounder MM, Zer A, Tap WD, Salah S, Dickson MA, Gupta AA, Keohan ML, Loong HH, D'Angelo SP, Baker S, Condy M, Nyquist-Schultz K, Tanner L, Erinjeri JP, Jasmine FH, Friedlander S, Carlson R, Unger TJ, Saint-Martin JR, Rashal T, Ellis J, Kauffman M, Shacham S, Schwartz GK, Abdul Razak AR. Phase IB Study of Selinexor, a First-in-Class Inhibitor of Nuclear Export, in Patients With Advanced Refractory Bone or Soft Tissue Sarcoma. J Clin Oncol. 2016 Sep 10;34(26):3166-74. doi: 10.1200/JCO.2016.67.6346. Epub 2016 Jul 25. Erratum In: J Clin Oncol. 2017 Mar;35(7):812.

Results Reference

derived

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A Phase I Trial to Assess the Effects of Food and Formulation on PK of KPT-330 in Patients With Sarcoma

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