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

NCT01896505 | Completed Phase 1 Results

• 1 other identifier: KCP-330-003
• Study Type: interventional
• Target: 54
• Locations: 2 countries
• Sites: 2

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 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.

Conditions

Sarcoma

Keywords

Bone sarcoma; Soft-tissue sarcoma; Sarcoma; KPT-330; Food; Effects; Selinexor

Outcome Measures

Primary Outcomes (7)

• Area Under the Concentration-time Curve From the Time Zero to the Last Non-zero Concentration (AUC0-t) of Selinexor

  AUC0-t was defined as area under the concentration-time curve from time zero to the last non-zero concentration.

  Day 1 of weeks 1-3 in Cycle 1: Pre-dose (within 10 minutes before swallowing study drug), 15, 30 minutes, 1, 1.5, 2, 3, 4, 5, 6, 8, 10,18, 24, and 48 hours post-dose

• Area Under the Concentration Time Curve From the Time Zero to Extrapolated to Infinity (AUC0-inf) of Selinexor

  AUC0-inf was defined as area under the concentration-time curve from time zero to infinity (extrapolated), AUC0-inf was calculated as AUC0-t + Ct/ elimination rate constant (kel), where: Ct = the last observed non- zero concentration.

  Day 1 of weeks 1-3 in Cycle 1: Pre-dose (within 10 minutes before swallowing study drug), 15, 30 minutes, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 18, 24, and 48 hours post-dose

• Maximum Observed Plasma Concentration (Cmax) of Selinexor

  Cmax was defined as maximum observed concentration, taken directly from the plasma concentration data.

  Day 1 of weeks 1-3 in Cycle 1: Pre-dose (within 10 minutes before swallowing study drug), 15, 30 minutes, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 18, 24, and 48 hours post-dose

• Time of First Maximum Observed Concentration (Tmax) of Selinexor

  Tmax was defined as time of first observation of Cmax, taken directly from the plasma concentration data.

  Day 1 of weeks 1-3 in Cycle 1: Pre-dose (within 10 minutes before swallowing study drug), 15, 30 minutes, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 18, 24, and 48 hours post-dose

• Terminal Phase Half-Life (t1/2) of Selinexor

  t1/2 was the terminal phase half-life, it was calculated as ln(2)/kel.

  Day 1 of weeks 1-3 in Cycle 1: Pre-dose (within 10 minutes before swallowing study drug), 15, 30 minutes, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 18, 24, and 48 hours post-dose

• Apparent Total Body Clearance (CL/F) of Selinexor

  Apparent total body clearance was calculated as Dose/AUC0-inf, uncorrected for fraction absorbed; reported normalized by participant body weight (kilogram \[kg\]).

  Day 1 of weeks 1-3 in Cycle 1: Pre-dose (within 10 minutes before swallowing study drug), 15, 30 minutes, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 18, 24, and 48 hours post-dose

• Apparent Volume of Distribution (Vd/F) of Selinexor

  Vd/F was calculated as Dose/ (kel \*AUC0-inf), uncorrected for fraction absorbed; reported normalized by participant body weight (kg).

  Day 1 of weeks 1-3 in Cycle 1: Pre-dose (within 10 minutes before swallowing study drug), 15, 30 minutes, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 18, 24, and 48 hours post-dose

Secondary Outcomes (11)

• Percentage of Participants With Best Overall Response According to Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 Criteria

  From the date of first documented response until the date of documented progression or last disease assessment (up to 39 months)

• Duration of Stable Disease as Per RECIST v1.1 Criteria

  From the date of first dose of study treatment to first documented radiologic evidence of disease recurrence or progression, censored date (up to 39 months)

• Progression Free Survival (PFS) as Per RECIST v1.1 Criteria

  From first dose of study treatment to time of disease progression or death, censored date (up to 39 months)

• Overall Survival (OS)

  From first dose of study treatment to death, censored date (up to 39 months)

• Time to Progression (TTP)

  From first dose of study treatment to first documented evidence of disease recurrence or progression, or death, censored date (up to 39 months)

Study Arms (6)

Arm 1

EXPERIMENTAL

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).

Drug: KCP-330

Arm 2

EXPERIMENTAL

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.

Drug: KCP-330

Arm 3

EXPERIMENTAL

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.

Drug: KCP-330

Arm 4

EXPERIMENTAL

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.

Drug: KCP-330

Arm 5

EXPERIMENTAL

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.

Drug: KCP-330

Arm 6

EXPERIMENTAL

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.

Drug: KCP-330

Interventions

KCP-330 DRUG

Also known as: Selinexor

Arm 1; Arm 2; Arm 3; Arm 4; Arm 5; Arm 6

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Karyopharm Therapeutics Inc: lead

Study Sites (2)

Memorial Sloan Kettering Cancer Centre

New York, New York, 10065, United States

Location

Princess Margaret Hospital

Toronto, Ontario, M5T 2M9, Canada

Location

Related Publications (1)

• 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.

  PMID: 27458288 DERIVED

MeSH Terms

Conditions

Sarcoma; Bone Neoplasms

Interventions

selinexor

Condition Hierarchy (Ancestors)

Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Bone Diseases; Musculoskeletal Diseases

Results Point of Contact

• Title: Jatin Shah, MD
• Organization: Karyopharm Therapeutics Inc

jshah@karyopharm.com

(617) 658-0600

Study Officials

• Michael Kauffman, MD, Ph.D

  Karyopharm Therapeutics Inc

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 11, 2013
• First Posted: July 11, 2013
• Study Start: July 30, 2013
• Primary Completion: October 21, 2016
• Study Completion: October 21, 2016
• Last Updated: January 8, 2024
• Results First Posted: January 8, 2024

Record last verified: 2023-03

Locations

CA (1); US (1)