Clinical trial NCT01896505: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Sarcoma
Keywords: Bone sarcoma
Soft-tissue sarcoma
Sarcoma
KPT-330
Food
Effects
Selinexor
Lead sponsor: Karyopharm Therapeutics Inc
Sponsor class: INDUSTRY
First posted: 2013-07-11
Enrollment: 54
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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

Primary outcomes:
measure: Area Under the Concentration-time Curve From the Time Zero to the Last Non-zero Concentration (AUC0-t) of Selinexor
timeFrame: 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
measure: Area Under the Concentration Time Curve From the Time Zero to Extrapolated to Infinity (AUC0-inf) of Selinexor
timeFrame: 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
measure: Maximum Observed Plasma Concentration (Cmax) of Selinexor
timeFrame: 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
measure: Time of First Maximum Observed Concentration (Tmax) of Selinexor
timeFrame: 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
measure: Terminal Phase Half-Life (t1/2) of Selinexor
timeFrame: 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
measure: Apparent Total Body Clearance (CL/F) of Selinexor
timeFrame: 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
measure: Apparent Volume of Distribution (Vd/F) of Selinexor
timeFrame: 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:
measure: Percentage of Participants With Best Overall Response According to Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 Criteria
timeFrame: From the date of first documented response until the date of documented progression or last disease assessment (up to 39 months)
measure: Duration of Stable Disease as Per RECIST v1.1 Criteria
timeFrame: 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)
measure: Progression Free Survival (PFS) as Per RECIST v1.1 Criteria
timeFrame: From first dose of study treatment to time of disease progression or death, censored date (up to 39 months)
measure: Overall Survival (OS)
timeFrame: From first dose of study treatment to death, censored date (up to 39 months)
measure: Time to Progression (TTP)
timeFrame: From first dose of study treatment to first documented evidence of disease recurrence or progression, or death, censored date (up to 39 months)
measure: Number of Participants With Growth Modulation Index (GMI) Less Than or Equal to (<=) 1.33 and Greater Than (>) 1.33
timeFrame: Up to 39 months
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs
timeFrame: From screening up to 30 days post last study drug dose (up to 39 months)
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity
timeFrame: From screening up to 30 days post last study drug dose (up to 39 months)
measure: Number of Participants With Clinically Significant Laboratory Abnormalities
timeFrame: From screening up to 30 days post last study drug dose (up to 39 months)
measure: Number of Participants With Clinically Significant Changes in Vital Signs
timeFrame: From screening up to 30 days post last study drug dose (up to 39 months)
measure: Number of Participants With Clinically Significant Changes in Electrocardiogram (ECGs)
timeFrame: From screening up to 30 days post last study drug dose
Other outcomes:
Locations:
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Centre
state: New York
city: Toronto
country: Canada
facility: Princess Margaret Hospital
state: Ontario
Study officials:
affiliation: Karyopharm Therapeutics Inc
name: Michael Kauffman, MD, Ph.D
role: STUDY_DIRECTOR
References:
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.