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

Karyopharm Therapeutics

Status and phase: Completed; Phase 1

Conditions: Sarcoma

Treatments: Drug: KCP-330

Study type: Interventional

Funder types: Industry

Identifiers

NCT01896505

KCP-330-003

Details and patient eligibility

About

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 and to compare PK of capsules and tablets in Arms 1 and 2; to evaluate tumor response in sarcoma participants in Arm 3; to compare the PK of 60 milligrams (mg) of the new, 2nd generation tablet formulation and 60 mg of the selinexor suspension formula to the current, 1st generation tablets.

Enrollment: 54 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

54 participants in 6 patient groups

Arm 1

Experimental group

Description:

Participants with advanced sarcomas (Liposarcoma, Leiomyosarcoma, and Other sarcoma) received Selinexor 30 milligrams per meter square (mg/m\^2) orally twice weekly in treatment sequence ABCD (Treatment A: fasted, tablet formulation on Day 1 of Week 1; Treatment B: high-fat meal, tablet formulation on Day 1 of Week 2; Treatment C: low-fat meal, tablet formulation on Day 1 of Week 3; Treatment D: low-fat meal, capsule formulation on Day 1 of Week 4 in Cycle 1 (Weeks 1 to 4).

Treatment:

Drug: KCP-330

Arm 2

Experimental group

Description:

Participants with advanced sarcomas (Liposarcoma, Leiomyosarcoma, and Other sarcoma) received selinexor 30 mg/m\^2 orally twice weekly in treatment sequence BADC (Treatment B: high-fat meal, tablet formulation on Day 1 of Week 1; Treatment A: fasted, tablet formulation on Day 1 of Week 2; Treatment D: low fat meal, capsule formulation on Day 1 of Week 3; Treatment C: low-fat meal, tablet formulation on Day 1 of Week 4 in Cycle 1 (Weeks 1 to 4).All participants received the current (1st generation) tablet formula at a dose of 60 mg on Day 3 of Weeks 1-3 of Cycle 1.

Treatment:

Drug: KCP-330

Arm 3

Experimental group

Description:

Participants with advanced sarcomas (Liposarcoma, Leiomyosarcoma, and Other sarcoma) received Selinexor 50 mg/m\^2 first generation tablets twice weekly on Days 1 and 3 of each week within 30 minutes of solid food consumption.

Treatment:

Drug: KCP-330

Arm 4

Experimental group

Description:

Participants with advanced sarcomas (Liposarcoma, Leiomyosarcoma, and Other sarcoma) received Selinexor 60 mg/m\^2 orally in treatment sequence ABC (Treatment A: current \[1st generation\] tablets on Day 1 of Week 1; Treatment B: new \[2nd generation\] tablets on Day 1 of Week 2; Treatment C: suspension dose of current \[1st generation\] tablets on Day 1 of Week 3 in Cycle 1 (Weeks 1 to 3). All participants received the current (1st generation) tablet formula at a dose of 60 mg on Day 3 of Weeks 1-3 of Cycle 1.

Treatment:

Drug: KCP-330

Arm 5

Experimental group

Description:

Participants with advanced sarcomas (Liposarcoma, Leiomyosarcoma, and Other sarcoma) received Selinexor 60 mg/m\^2 orally in treatment sequence CAB (Treatment C: suspension dose of current \[1st generation\] tablets on Day 1 of Week 1; Treatment A: current \[1st generation\] tablets on Day 1 of Week 2; Treatment B: new \[2nd generation\] tablets on Day 1 of Week 3 in Cycle 1 (Weeks 1 to 3). All participants received the current (1st generation) tablet formula at a dose of 60 mg on Day 3 of Weeks 1-3 of Cycle 1.

Treatment:

Drug: KCP-330

Arm 6

Experimental group

Description:

Participants with advanced sarcomas (Liposarcoma, Leiomyosarcoma, and Other sarcoma) received Selinexor 60 mg/m\^2 orally in treatment sequence BCA (Treatment B: new \[2nd generation\] tablets on Day 1 of Week 1; Treatment C: suspension dose of current \[1st generation\] tablets on Day 1 of Week 2; Treatment A: current \[1st generation\] tablets on Day 1 of Week 3 in Cycle 1 (Weeks 1 to 3). All participants received the current (1st generation) tablet formula at a dose of 60 mg on Day 3 of Weeks 1-3 of Cycle 1.

Treatment:

Drug: KCP-330