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

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2013 by Karyopharm Therapeutics, Inc
Sponsor:
Information provided by (Responsible Party):
Karyopharm Therapeutics, Inc
ClinicalTrials.gov Identifier:
NCT01896505
First received: June 11, 2013
Last updated: January 15, 2015
Last verified: September 2013
  Purpose

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).


Condition Intervention Phase
Sarcoma
Drug: KCP-330
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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 Witn Soft-Tissue or Bone Sarcoma

Resource links provided by NLM:


Further study details as provided by Karyopharm Therapeutics, Inc:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]
  • Peak Plasma Concentration (Cmax) 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 ] [ Designated as safety issue: Yes ]
  • Comparison of AUC and Cmax of KPT-330 between: Treatment A vs B; Treatment C vs D; Treatment A vs C [ 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 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • 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. ] [ Designated as safety issue: Yes ]
  • Change in laboratory parameters (serum chemistry, hematology and urinalysis) [ Time Frame: Baseline and Day 1 of weeks 1 -4 in Cycle 1 ] [ Designated as safety issue: Yes ]
  • Change in ECG parameters [ Time Frame: Baseline and Day 1 of each week (weeks 1-4) in Cycle 1 ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: Yes ]
  • Number and percentages of patients involved per CTCAE Category and CTCAE Term [ Time Frame: After first dose of drug until final study visit ] [ Designated as safety issue: Yes ]
  • Highest relation of an AE to study drug [ Time Frame: After first dose until final visit ] [ Designated as safety issue: Yes ]
  • Maximum AE severity [ Time Frame: After first dose of study drug until the final study visit ] [ Designated as safety issue: Yes ]

Other Outcome Measures:
  • Biomarker changes on sarcoma biopsy specimens (in patients who can safely undergo biopsy). [ Time Frame: Baseline and Week 3 or 4 of Cycle 1 ] [ Designated as safety issue: No ]

Estimated Enrollment: 53
Study Start Date: July 2013
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: November 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm 1 - Treatment A, B, C, D

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)

Drug: KCP-330
Other Name: Selinexor
Experimental: Arm 2 - Treatment B, A, D, C

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)

Drug: KCP-330
Other Name: Selinexor
Experimental: Arm 3

To evaluate tumor response in sarcoma patients (RECIST v1.1 criteria) on KCP-330.

(Note that recruitment has been completed for this arm)

Drug: KCP-330
Other Name: Selinexor
Experimental: Arm 4 - Treatment A, B, 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 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

Drug: KCP-330
Other Name: Selinexor
Experimental: Arm 5 - Treatment C, A, 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 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

Drug: KCP-330
Other Name: Selinexor
Experimental: Arm 6 - Treatment B, C, A

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

Drug: KCP-330
Other Name: Selinexor

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. 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.
  2. 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:

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

Please refer to this study by its ClinicalTrials.gov identifier: NCT01896505

Contacts
Contact: Michael Kauffman, MD PhD +1 508-975-4822 mkauffman@karyopharm.com

Locations
United States, New York
Memorial Sloan Kettering Cancer Centre Recruiting
New York, New York, United States, 10065
Contact    212-639-2000      
Principal Investigator: Gary Schwartz, M.D.         
Canada, Ontario
Princess Margaret Hospital Recruiting
Toronto, Ontario, Canada, M5T 2M9
Contact    416 946 2000      
Principal Investigator: Malcolm J Moore, M.D.         
Sponsors and Collaborators
Karyopharm Therapeutics, Inc
  More Information

No publications provided

Responsible Party: Karyopharm Therapeutics, Inc
ClinicalTrials.gov Identifier: NCT01896505     History of Changes
Other Study ID Numbers: KCP-330-003
Study First Received: June 11, 2013
Last Updated: January 15, 2015
Health Authority: United States: Food and Drug Administration
Canada: Health Canada

Keywords provided by Karyopharm Therapeutics, Inc:
bone
soft-tissue
sarcoma
KPT-330
food
effects
Selinexor

Additional relevant MeSH terms:
Sarcoma
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Connective and Soft Tissue

ClinicalTrials.gov processed this record on July 01, 2015