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

Study Overview
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Brief Summary
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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).

Official Title
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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

Conditions
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Sarcoma

Intervention / Treatment
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* Drug: KCP-330


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1 - Treatment A, B, C, D<br>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<br> <br> * Other names: Selinexor;|
| Experimental: Arm 2 - Treatment B, A, D, C<br>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<br> <br> * Other names: Selinexor;|
| Experimental: Arm 3<br>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<br> <br> * Other names: Selinexor;|
| Experimental: Arm 4 - Treatment A, B, C<br>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<br> <br> * Other names: Selinexor;|
| Experimental: Arm 5 - Treatment C, A, B<br>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<br> <br> * Other names: Selinexor;|
| Experimental: Arm 6 - Treatment B, C, A<br>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<br> <br> * Other names: Selinexor;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the plasma concentration versus time curve (AUC) of KPT-330 |  | 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 Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tumor response in sarcoma patients (RECISTv1.1 criteria) |  | 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. | 
| Change in laboratory parameters (serum chemistry, hematology and urinalysis) |  | Baseline and Day 1 of weeks 1 -4 in Cycle 1 | 
| Change in ECG parameters |  | Baseline and Day 1 of each week (weeks 1-4) in Cycle 1 | 
| Change in Vital sign parameters (Systolic pressure, diastolic pressure and heart rate) |  | Baseline and on Day 1 of each week (weeks 1 - 4) of Cycle 1 | 
| Number and percentages of patients involved per CTCAE Category and CTCAE Term |  | After first dose of drug until final study visit | 
| Highest relation of an AE to study drug |  | After first dose until final visit | 
| Maximum AE severity |  | After first dose of study drug until the final study visit | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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bone, soft-tissue, sarcoma, KPT-330, food, effects, Selinexor