Neoplasms

All Conditions

Rare Diseases

Osteosarcoma

Sarcoma

Neoplasms, Connective and Soft Tissue

Neoplasms by Histologic Type

Soft Tissue Sarcoma

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).

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.

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.

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.

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.

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.

KCP-330

Michael Kauffman, MD, Ph.D

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.

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

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

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

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.

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

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

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

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

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

Best overall response rate was defined as the percentage of participants who achieved complete response (CR), and partial response (PR), as assessed by the RECIST v1.1 criteria. CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non target) must have reduction in the short axis to less than (\<) 10 millimeter (mm). PR was defined as At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum longest diameter (LD).

Duration of at least stable disease was defined as the time from the date of first dose of study treatment to first documented radiologic evidence of disease recurrence or progression as per RECIST v1.1 Criteria. Participants without evidence of progression were censored at time of last disease assessment. Progressive Disease (PD) was defined as at least a 20% increase in the sum of diameters of measured lesions taking as references the smallest sum of diameters recorded since the treatment started. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Appearance of one or more new lesions also constituted progressive disease.

PFS was defined as the time from the date of randomization until the first date of Independent Review Committee (IRC)-confirmed PD per RECIST v1.1, or death due to any cause. PD was defined as at least a 20% increase in the sum of the longest diameter (SLD), taking as reference the smallest sum of the longest diameter (SLD) recorded from baseline or the appearance of 1 or more new lesions. Participants who were last known to be alive and without evidence of progression were censored at time of last disease assessment. If date of progression or death occurred after more than 1 missed disease assessment interval, or 30 days after end of treatment, participants were censored at the time of last evaluable disease assessment prior to the missed assessment.

OS was defined as the time from date first dose of study treatment to the date of death. Participants who were still alive prior to the data cutoff for final efficacy analysis, or who dropped out prior to study end, were censored at the day they were last known to be alive.

TTP was defined as the time from date of first dose of study treatment to first documented evidence of disease recurrence or progression, or death due to disease progression, whichever occurred first. Participants without evidence of progression were censored at time of last evaluable disease assessment.

GMI was defined as the ratio between the TTP with selinexor and the TTP with the most recent prior treatment. GMI was calculated, using a previously described threshold of 1.3 or greater as a sign of potential drug activity and improved overall survival.

An AE was any untoward medical occurrence in a participant administered a pharmaceutical product during the course of a study and which does not necessarily have to have a causal relationship with this treatment. SAE defined as any AE, occurring at any dose (including after the informed consent form was signed and prior to dosing) that and regardless of causality that: results in death, is life-threatening (participant was at immediate risk of death from event as it occurred), requires in-patient hospitalization (formal admission to a hospital for medical reasons) or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, results in a congenital anomaly/birth defect. TEAE was defined as any AE with onset or worsening of a pre-existing condition on or after the first administration of study treatment through 30 days following last dose or any event considered drug-related by the investigator through the end of the study.

AE was defined as the appearance of (or worsening of any pre-existing) undesirable sign, symptom, or medical condition that occur after participant's signed informed consent obtained. TEAE was defined as any AE with onset or worsening of a pre-existing condition on or after the first administration of study treatment through 28 days following last dose or any event considered drug-related by the investigator through the end of the study. Grade refers to the severity of the AE. The CTCAE displays Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1: mild, Grade 2: moderate, Grade 3: severe, Grade 4: life-threatening, and Grade 5: death.

Number of participants with clinically significant laboratory abnormalities including clinical chemistry, hematology, coagulation and urinalysis. Number of participants with clinically significant laboratory abnormalities which were deemed clinically significant by the investigator were reported.

Vital signs included blood pressure (systolic blood pressure and diastolic blood pressure). Measurements were made after the participant had been resting supine for a minimum of 5 minutes. Clinically significant findings were defined as such in the opinion of the investigator occurring at any time on treatment from normal pre-dose based on the condition met (Yes/No). Number of participants with clinically significant changes in vital signs with condition (Yes) were only reported.

Twelve lead ECGs were obtained after the participant has rested in a supine position for at least 5 minutes. Clinically significant findings were defined as such in the opinion of the investigator or designated physician occurring at any time on treatment from normal pre-dose.

Karyopharm Therapeutics Inc

Safety population consisted of all participants who received at least one dose of selinexor. As pre-specified in SAP, safety data was collected and analyzed as per the individual arms with specified treatment sequences only.

Arm 1:

Arm 2:

Arm 3:

Arm 4:

Arm 5:

Arm 6:

Participants with advanced sarcomas (Liposarcoma, Leiomyosarcoma, and Other sarcoma) received selinexor 30 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).

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).

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.

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.

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.

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.

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

American Indian or Alaska Native

Asian

Native Hawaiian or Other Pacific Islander

Black or African American

White

Unknown or Not Reported

Other

Race/Ethnicity, Customized

Safety population consisted of all participants who received at least one dose of selinexor.

Jatin Shah, MD

Participants with advanced sarcomas (Liposarcoma, Leiomyosarcoma, and Other sarcoma) received selinexor 30 mg/m\^2 orally twice weekly in randomized treatment sequence (i.e. Treatment A: fasted, tablet formulation on Day 1 \[Week 1\] in Arm 1 and Day 1 \[Week 2\] in Arm 2).

Arms 1 and 2: Treatment A: Fasted, Tablet Formulation

Participants with advanced sarcomas (Liposarcoma, Leiomyosarcoma, and Other sarcoma) received selinexor 30 mg/m\^2 orally twice weekly in randomized treatment sequence (i.e. Treatment B: high-fat meal, tablet formulation on Day 1 \[Week 2\] in Arm 1 and Day 1 \[Week 1\] in Arm 2).

Arms 1 and 2: Treatment B: High-Fat Meal, Tablet Formulation

Participants with advanced sarcomas (Liposarcoma, Leiomyosarcoma, and Other sarcoma) received selinexor 30 mg/m\^2 orally twice weekly in randomized treatment sequence (i.e. Treatment C: low-fat meal, tablet formulation on Day 1 \[Week 3\] in Arm 1 and Day 1 \[Week 4\] in Arm 2).

Arms 1 and 2: Treatment C: Low-Fat Meal, Tablet Formulation

Participants with advanced sarcomas (Liposarcoma, Leiomyosarcoma, and Other sarcoma) received selinexor 30 mg/m\^2 orally twice weekly in randomized treatment sequence (i.e. Treatment D: low-fat meal, capsule formulation on Day 1 \[Week 4\] in Arm 1 and Day 1 \[Week 3\] in Arm 2).

Arms 1 and 2: Treatment D: Low-Fat Meal, Capsule Formulation

Participants with advanced sarcomas (Liposarcoma, Leiomyosarcoma, and Other sarcoma) received Selinexor 60 mg/m\^2 orally in randomized treatment sequence (i.e. Treatment A: current \[1st generation\] tablets on Day 1 and 3 in Arm 4, 5 and 6 for Cycle 1 (Weeks 1 to 3).

Arms 4, 5, and 6: Treatment A: First Generation Tablet

Participants with advanced sarcomas (Liposarcoma, Leiomyosarcoma, and Other sarcoma) received Selinexor 60 mg/m\^2 orally in randomized treatment sequence (i.e. Treatment B: new \[2nd generation\] tablets on Day 1 in Arm 4, 5 and 6 for (Weeks 1 to 3).

Arms 4, 5, and 6: Treatment B: Second Generation Tablet

Participants with advanced sarcomas (Liposarcoma, Leiomyosarcoma, and Other sarcoma) received selinexor 60 mg/m\^2 orally in randomized treatment sequence (i.e. Treatment C: suspension dose of current \[1st generation\] tablets on Day 1 and 3 in Arm 4, 5 and 6 for (Weeks 1 to 3).

Arms 4, 5, and 6: Treatment C: Oral Suspension

Pharmacokinetic (PK) population included all participants in Arms 1, 2 and Arms 4, 5, and 6 who received selinexor, and for whom the PK profile for all treatments could be adequately characterized. Here 'overall number of participants analyzed' signifies number of participants evaluable for this outcome measure. As pre-specified in SAP and protocol Arm 3 was a non-PK group assessment, so data was not collected and analyzed for this PK outcome.

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

Participants with advanced sarcomas (Liposarcoma, Leiomyosarcoma, and Other sarcoma) received Selinexor 30 mg/m\^2 orally twice weekly in randomized treatment sequence (i.e. Treatment A: fasted, tablet formulation on Day 1 \[Week 1\] in Arm 1 and Day 1 \[Week 2\] in Arm 2).

Participants with advanced sarcomas (Liposarcoma, Leiomyosarcoma, and Other sarcoma) received Selinexor 30 mg/m\^2 orally twice weekly in randomized treatment sequence (i.e. Treatment B: high-fat meal, tablet formulation on Day 1 \[Week 2\] in Arm 1 and Day 1 \[Week 1\] in Arm 2).

Participants with advanced sarcomas (Liposarcoma, Leiomyosarcoma, and Other sarcoma) received Selinexor 30 mg/m\^2 orally twice weekly in randomized treatment sequence (i.e. Treatment C: low-fat meal, tablet formulation on Day 1 \[Week 3\] in Arm 1 and Day 1 \[Week 4\] in Arm 2).

Participants with advanced sarcomas (Liposarcoma, Leiomyosarcoma, and Other sarcoma) received Selinexor 30 mg/m\^2 orally twice weekly in randomized treatment sequence (i.e. Treatment D: low-fat meal, capsule formulation on Day 1 \[Week 4\] in Arm 1 and Day 1 \[Week 3\] in Arm 2).

PK population included all participants in Arms 1, 2 and Arms 4, 5, and 6 who received selinexor, and for whom the PK profile for all treatments could be adequately characterized. Here 'overall number of participants analyzed' signifies participants who are evaluable for this outcome measure. As pre-specified in SAP and protocol Arm 3 was a non-PK group assessment, so data was not collected and analyzed for this PK outcome.

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

Maximum Observed Plasma Concentration (Cmax) of Selinexor

Participants with advanced sarcomas (Liposarcoma, Leiomyosarcoma, and Other sarcoma) received Selinexor 30 mg/m\^2 orally twice weekly in randomized treatment sequence (i.e. (i.e. Treatment A: fasted, tablet formulation on Day 1 \[Week 1\] in Arm 1 and Day 1 \[Week 2\] in Arm 2).

Time of First Maximum Observed Concentration (Tmax) of Selinexor

Participants with advanced sarcomas (Liposarcoma, Leiomyosarcoma, and Other sarcoma) received selinexor 60 mg/m\^2 orally in randomized treatment sequence (i.e. Treatment A: current \[1st generation\] tablets on Day 1 and 3 \[Week 1 and 3\] in Arm 4 and 6 and Day 1 \[Week 2\] in Arm 2 for one cycle (Weeks 1 to 3).

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

Apparent Total Body Clearance (CL/F) of Selinexor

Apparent Volume of Distribution (Vd/F) of Selinexor

Complete Response (CR)

Partial Response (PR)

Participants with liposarcoma received selinexor 30 mg/m\^2 orally twice weekly in randomized treatment sequence (A, B, C, D) in Arm 1 and 2 for one cycle (Weeks 1 to 4); 50 mg/m\^2 first generation tablets twice weekly on Days 1 and 3 in Arm 3; 60 mg/m\^2 orally in randomized treatment sequence (A, B, C) on Day 1 and 3 for 1st generation tablets and Day 1 for 2nd generation tablets for one cycle (Weeks 1 to 3).

Liposarcoma

Participants with leiomyosarcoma received selinexor 30 mg/m\^2 orally twice weekly in randomized treatment sequence (A, B, C, D) in Arm 1 and 2 for one cycle (Weeks 1 to 4); 50 mg/m\^2 first generation tablets twice weekly on Days 1 and 3 in Arm 3; 60 mg/m\^2 orally in randomized treatment sequence (A, B, C) on Day 1 and 3 for 1st generation tablets and Day 1 for 2nd generation tablets for one cycle (Weeks 1 to 3).

Leiomyosarcoma

Participants with Other sarcoma received selinexor 30 mg/m\^2 orally twice weekly in randomized treatment sequence (A, B, C, D) in Arm 1 and 2 for one cycle (Weeks 1 to 4); 50 mg/m\^2 first generation tablets twice weekly on Days 1 and 3 in Arm 3; 60 mg/m\^2 orally in randomized treatment sequence (A, B, C) on Day 1 and 3 for 1st generation tablets and Day 1 for 2nd generation tablets for one cycle (Weeks 1 to 3).

Other Sarcoma

Safety population consisted of all participants who received at least one dose of selinexor. Data for this outcome measure analysis was planned to be analyzed as per disease specific sarcoma.

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

Safety population consisted of all participants who received at least one dose of selinexor. Data for this outcome measure was planned to be analyzed as per disease specific sarcoma.

Duration of Stable Disease as Per RECIST v1.1 Criteria

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

Overall Survival (OS)

Time to Progression (TTP)

GMI <= 1.33

GMI > 1.33

Safety population consisted of all participants who received at least one dose of selinexor. Data for this outcome measure was planned to be analyzed as per disease specific sarcoma. Here 'overall number of participants analyzed' signifies participants who were evaluable for this outcome measure.

Number of Participants With Growth Modulation Index (GMI) Less Than or Equal to (<=) 1.33 and Greater Than (>) 1.33

Participants with TEAEs

Participants with Serious TEAEs

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).

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: lowfat 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).

Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs

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).

Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity

Hematology

Clinical Chemistry

Coagulation: Prothrombin intl. normalized ratio

Urinalysis

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.

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

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

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