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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT01607892
Other study ID # KCP-330-001
Secondary ID
Status Completed
Phase Phase 1
First received
Last updated
Start date July 23, 2012
Est. completion date October 13, 2015

Study information

Verified date January 2023
Source Karyopharm Therapeutics Inc
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

The purpose of this research study is to find out more information relating to the highest dose of KCP-330 that can be given safely and side effects it may cause, to examine how the body affects KCP-330 concentrations in the blood (pharmacokinetics or PK), to examine the effects of KCP-330 on the body (pharmacodynamics or PDn) and to obtain information on its effectiveness in treating cancer.


Recruitment information / eligibility

Status Completed
Enrollment 286
Est. completion date October 13, 2015
Est. primary completion date October 13, 2015
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility Inclusion Criteria 1. Malignancies that are refractory to or intolerant of established therapy known to provide clinical benefit. Patients must not be candidates for anti-tumor regimes known to provide clinical benefit. 2. All patients must have evidence of progressive disease on study entry. Previously untreated patients who are not chemotherapy candidates on Arm 2 may have advanced disease (without clear progression). There is no upper limit on the number of prior treatments provided that all inclusion criteria are met, and exclusion criteria are not met. Exclusion Criteria 1. Radiation, chemotherapy, or immunotherapy or any other anticancer therapy =2 weeks prior to cycle 1 day 1 and mitomycin C and radioimmunotherapy 6 weeks prior to cycle 1 day 1. 2. Patients with active graft versus host disease after allogeneic stem cell transplantation. At least 3 months must have elapsed since completion of allogeneic stem cell transplantation except for patients with AML, where at least 2 months must have elapsed; 3. Known active hepatitis A, B, or C infection; or known to be positive for HCV RNA or HBsAg (HBV surface antigen); 4. Patients with active CNS malignancy. Asymptomatic small lesions are not considered active. Treated lesions may be considered inactive if they are stable for at least 3 months. Patient with malignant cells in their cerebrospinal fluid (CSF) without CNS symptom may be included. 5. Significantly diseased or obstructed gastrointestinal tract or uncontrolled vomiting or diarrhea. 6. Grade =2 peripheral neuropathy at baseline (within 14 days prior to cycle 1 day 1). 7. Macular degeneration, uncontrolled glaucoma, or markedly decreased visual acuity. 8. In the opinion of the investigator, patients who are significantly below their ideal body weight.

Study Design


Intervention

Drug:
KPT-330


Locations

Country Name City State
Canada Tom Baker Cancer Centre Calgary Alberta
Canada Princess Margaret Hospital Toronto Ontario
Denmark Rigshospitalet Copenhagen
United States Dana-Farber Cancer Institute Boston Massachusetts
United States Gabrail Cancer Center Research Canton Ohio
United States The Ohio State University Columbus Ohio
United States Hackensack University Medical Center Hackensack New Jersey
United States MD Anderson Cancer Center Houston Texas
United States Sarah Cannon Research Institute Nashville Tennessee
United States Weill Cornell Medical Center New York New York
United States Washington University School of Medicine Saint Louis Missouri
United States Moffitt Cancer Center Tampa Florida

Sponsors (1)

Lead Sponsor Collaborator
Karyopharm Therapeutics Inc

Countries where clinical trial is conducted

United States,  Canada,  Denmark, 

Outcome

Type Measure Description Time frame Safety issue
Primary Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) An adverse event (AE) was any untoward medical occurrence in a clinical investigation 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. An Serious adverse event (SAE) was an AE resulting in any of the following outcomes: death; life-threatening event; required or prolonged inpatient hospitalization; persistent or significant disability/incapacity; congenital anomaly. TEAEs are any untoward medical incidence in a participant during administered study treatment, whether or not these events were related to study treatment. From first dose of study drug administration to end of treatment (up to 27 months)
Primary Recommended Phase 2 Dose (RP2D) of Selinexor Recommended Phase 2 dose was determined by maximum tolerated dose (MTD). MTD was defined as the next lower dose level below the one in which > 1 of 3 participants or = 2 of 6 participants experienced dose-limiting toxicity (DLT), provided that that dose level is =25% lower than the highest dose tested. If the projected MTD was >25% lower than the highest dose tested, then an additional cohort of =3 participants were added at a dose that was intermediate between the intolerable dose and the next lower dose. From first dose of study drug administration to end of treatment (up to 27 months)
Secondary Maximum Observed Plasma Concentration (Cmax) of Selinexor Cmax was defined as the maximum observed concentration, taken directly from the plasma concentration. 0 (pre-dose), 0.5, 1, 2, 4, 8, 24 and 48 hours post-dose on Day 1, 8 of Cycle 1 and Days 15, 16 or 17 of Cycle 2
Secondary Time to Maximum Observed Concentration (Tmax) of Selinexor Tmax was defined as time of first observation of Cmax, taken directly from the plasma concentration data. 0 (pre-dose), 0.5, 1, 2, 4, 8, 24 and 48 hours post-dose on Day 1, 8 of Cycle 1 and Days 15, 16 or 17 of Cycle 2
Secondary Average Concentration From Time 0 to 24 Hours (Cavg0-24h) of Selinexor Cavg0-24h was defined as average concentration from time 0 to 24 hours. 0 (pre-dose), 0.5, 1, 2, 4, 8, 24 and 48 hours post-dose on Day 1, 8 of Cycle 1 and Days 15, 16 or 17 of Cycle 2
Secondary Area Under the Concentration-Time Curve From Time 0 to t (AUC0-t) of Selinexor AUC0-t was defined as area under the concentration-time curve from time zero to the last non-zero concentration. 0 (pre-dose), 0.5, 1, 2, 4, 8, 24 and 48 hours post-dose on Day 1, 8 of Cycle 1 and Days 15, 16 or 17 of Cycle 2
Secondary Area Under the Concentration-Time Curve From Time 0 Extrapolated to Infinity (AUC0-inf) of Selinexor AUC0-inf was defined as the area under the concentration-time curve from time zero to infinity (extrapolated). 0 (pre-dose), 0.5, 1, 2, 4, 8, 24 and 48 hours post-dose on Day 1, 8 of Cycle 1 and Days 15, 16 or 17 of Cycle 2
Secondary Apparent Volume of Distribution Uncorrected for Fraction Absorbed (Vd/F) of Selinexor Apparent volume of distribution was calculated as Dose/ (kel *AUC0-inf), uncorrected for fraction absorbed, reported normalized by participant body weight (kilogram [kg]). 0 (pre-dose), 0.5, 1, 2, 4, 8, 24 and 48 hours post-dose on Day 1, 8 of Cycle 1 and Days 15, 16 or 17 of Cycle 2
Secondary Apparent Total Body Clearance, Uncorrected for Fraction Absorbed (Cl/F) of Selinexor Cl/F was calculated as Dose/AUC0-inf, uncorrected for fraction absorbed, reported normalized by participant body weight (kg). 0 (pre-dose), 0.5, 1, 2, 4, 8, 24 and 48 hours post-dose on Day 1, 8 of Cycle 1 and Days 15, 16 or 17 of Cycle 2
Secondary Terminal Half-Life (t½) of Selinexor t½ was, calculated as ln(2)/kel, where kel is elimination rate constant, calculated using linear regression on the terminal portion of the log-linear concentration versus time curve. 0 (pre-dose), 0.5, 1, 2, 4, 8, 24 and 48 hours post-dose on Day 1, 8 of Cycle 1 and Days 15, 16 or 17 of Cycle 2
Secondary Number of Participants With Overall Response of Selinexor Objective response for each malignancy was defined using the disease response criteria by malignancy; For NHL (including DLBCL, PTCL, and CTCL), objective response included complete response (CR) and partial response (PR). For MM, objective response included stringent complete response (sCR), CR, very good partial response (VGPR), and PR. For WM, objective response included CR, VGPR, and PR. For CLL, ALL, and AML, objective response included complete remission and Partial remission. For CML, objective response includes complete cytogenic response, and complete hematologic response (CHR). From first dose of study drug administration to end of treatment (up to 27 months)
Secondary Duration of Response Duration of response was defined as the time from the first occurrence of objective response to first documented evidence of disease recurrence or progression. Participants without evidence of progression were censored at time of last evaluable disease assessment. Objective response was defined as any response of partial response/remission or better for all malignancies; for AML, a response of morphologic leukemia-free state is also included for ORR. Duration of response was calculated by Kaplan-Meier method. From first dose of study drug administration to end of treatment (up to 27 months)
Secondary Progression-free Survival Progression-free survival (PFS) was calculated from the date of first dose of study drug to first documented evidence of disease recurrence or progression or death due to any cause. Participants who were last known to be alive and without evidence of progression were censored at time of last evaluable disease assessment. If date of progression or death occurred after more than 1 missed disease assessment interval, participants were censored at the time of last evaluable disease assessment prior to the missed assessment. Cycle 1 Day 1 to End of Treatment (up to 27 months)
Secondary Duration of at Least Stable Disease Duration of at least stable disease was defined as the time from the date of first dose of study drug to first documented evidence of disease recurrence or progression. Participants without evidence of progression were censored at time of last evaluable disease assessment. Cycle 1 Day 1 to End of Treatment (up to 27 months)
Secondary Overall Survival Overall Survival was calculated from the date of first dose of study drug to date of death due to any cause. Participants who were last known to be alive were censored at time of last contact. Overall survival was calculated by Kaplan-Meier method. Cycle 1 Day 1 to End of Treatment (up to 27 months)
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