Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

All Conditions

Gland and Hormone Related Diseases

Rare Diseases

Uterine Cervical Neoplasms

Carcinoma

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Endometrial Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Uterine Neoplasms

Genital Neoplasms, Female

Urogenital Neoplasms

Uterine Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Ovarian Cancer

Ovarian Epithelial Cancer

Participants with ovarian carcinoma who were platinum refractory or platinum resistant and had received at least one line of chemotherapy for relapsed disease received a dose of 50 milligram per meter square (mg/m\^2) of selinexor oral tablets twice weekly (BIW) (doses at least 36 hours apart) with light meal and 120 milliliters (mL) of water in a 4-week treatment cycles. After 12 weeks of treatment, a dose of 60 mg/m\^2 of selinexor oral tablets BIW were administrated if the participants had no major toxicity. During dose reduction, participants received a minimum dose of 35 mg/m\^2 once weekly (QW). This treatment continued until progression of disease (PD) or unacceptable toxicity or any discontinuation criteria or withdrawal of consent by the participant, or non-compliance by the participant with protocol requirements.

Participants with endometrial carcinoma who had received at least one line of chemotherapy for relapsed or advanced (Stage IVb, IIIc) disease received a dose of 50 mg/m\^2 of selinexor oral tablets BIW (doses at least 36 hours apart) with light meal and 120 mL of water in a 4-week treatment cycles. After 12 weeks of treatment, a dose of 60 mg/m\^2 of selinexor oral tablets BIW were administrated if the participants had no major toxicity. During dose reduction, participants received a minimum dose of 35 mg/m\^2 QW. This treatment continued until PD or unacceptable toxicity or any discontinuation criteria or withdrawal of consent by the participant, or non-compliance by the participant with protocol requirements.

Participants with cervical carcinoma who had received at least one line of chemotherapy for relapsed or advanced (Stage IV) disease received a dose of 50 mg/m\^2 of selinexor oral tablets BIW (doses at least 36 hours apart) with light meal and 120 mL of water in a 4-week treatment cycles. After 12 weeks of treatment, a dose of 60 mg/m\^2 of selinexor oral tablets BIW were administrated if the participants had no major toxicity. During dose reduction, participants received a minimum dose of 35 mg/m\^2 QW. This treatment continued until PD or unacceptable toxicity or any discontinuation criteria or withdrawal of consent by the participant, or non-compliance by the participant with protocol requirements.

Participants with ovarian carcinoma who were platinum refractory or platinum resistant and had received at least one line of chemotherapy for relapsed disease received a dose of 35 mg/m\^2 of selinexor oral tablets BIW (doses at least 36 hours apart) with light meal and 120 mL of water in a 4-week treatment cycles. After 6 weeks of treatment, a dose of 50 mg/m\^2 of selinexor oral tablets BIW were administrated if the participants had no major toxicity. During dose reduction, participants received a minimum dose of 35 mg/m\^2 QW. This treatment continued until PD or unacceptable toxicity or any discontinuation criteria or withdrawal of consent by the participant, or non-compliance by the participant with protocol requirements.

Participants with ovarian carcinoma who were platinum refractory or platinum resistant and had received at least one line of chemotherapy for relapsed disease received a dose of 50 mg/m\^2 of selinexor oral tablets QW (doses at least 5 days apart) with light meal and 120 mL of water in a 4-week treatment cycles. After 6 weeks of treatment, a dose of 60 mg/m\^2 of selinexor oral tablets QW were administrated if the participants had no major toxicity. During dose reduction, participants received a minimum dose of 35 mg/m\^2 QW. This treatment continued until PD or unacceptable toxicity or any discontinuation criteria or withdrawal of consent by the participant, or non-compliance by the participant with protocol requirements.

Route of administration and dosage form: Oral tablet; Doses: 35 mg/m\^2 BIW, 35 mg/m\^2 QW, 50 mg/m\^2 BIW, 50 mg/m\^2 QW, 60 mg/m\^2 BIW, 60 mg/m\^2 QW.

Treatment cycles were 4 weeks each i.e., 28 day cycles.

Selinexor

The primary trial objective is to determine the efficacy of KPT-330 (selinexor) in participants with advanced or metastatic gynaecological cancers by disease control rate (complete response (CR) or partial response (PR) or stable disease (SD) for at least 12 weeks, assessed according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.

Two-stage Phase 2 study in 3 separate gynecological cancer cohorts, with an additional set of participants in the ovarian cohort randomized into 2 different treatment regimens. The study is divided between a Primary Treatment Phase and a Maintenance Phase with each phase supported by a separate database.

Part 1 - Three parallel cohorts of participants with ovarian (Cohort A), endometrial (Cohort B), or cervical (Cohort C) carcinoma were enrolled.

Part 2 - Based on the observed tolerability and efficacy profile in the ongoing ovarian cohort (Cohort A), 2 additional treatment schedules will be explored to optimize the dosing schedule in a participant population with ovarian carcinoma.

Study of KPT-330 (Selinexor) in Female Patients With Advanced Gynaecologic Malignancies

A Phase II, Open-label Study of Efficacy and Safety of the Selective Inhibitor of Nuclear Export/SINE™ Compound KPT-330 (Selinexor) in Patients With Advanced Gynaecologic Malignancies

Disease Control Rate (DCR) was defined as the point estimate of the percentage of participants who had complete response (CR), partial response (PR), or stable disease (SD) for at least 12 weeks, assessed according to RECIST v1.1. CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (\<) 10 millimeters (mm). PR was defined as at least a 30 percent (%) decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. Participants without documented disease progression were censored on the date of last radiologic assessment.

Overall Response Rate (ORR) was defined as the point estimate of the percentage of participants who had CR or PR, assessed according to RECIST v1.1. CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) had reduction in short axis to \<10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

DCR was defined as the point estimate of the percentage of participants who had CR, PR, or SD for at least 12 weeks, assessed according to GCIG response criteria (RECIST v1.1 and CA-125).

ORR was defined as the point estimate of the percentage of participants who had CR or PR, assessed according to GCIG response criteria (RECIST v1.1 and CA-125).

PFS was defined as the time from date of start of study therapy to the date of tumor disease progression (i.e., radiological only) or date of death due to any cause. Participants without documented disease progression were censored at the time of last radiologic assessment. Participants without any post baseline assessments were censored at date of start of study therapy.

OS was defined as time from the date of start of study therapy to the date of death due to any cause. Participants who were alive at the time of the analysis or were lost to follow-up were censored at the day they were last known to be alive. Kaplan-Maier method was used for estimation.

OS rate was reported as the percentage of participants who were alive at 12 and 24 months. OS was defined as time from the date of start of study therapy to the date of death due to any cause. Participants who were alive at the time of the analysis or are lost to follow-up were censored at the day they were last known to be alive. Survival rate were estimated by Kaplan-Maier method.

An adverse event (AE) was defined as any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product, whether or not it is considered related to the medicinal product. A serious adverse event (SAE) was defined as an AE that meets one or more of the mentioned criteria, i.e., fatal, life threatening (places the participants at immediate risk of death), required in-patient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, congenital anomaly/birth defect, or important medical events. TEAE was defined as any AE (serious/non-serious) with onset or worsening of a pre-existing condition on or after the first administration of study medication through 30 days following last dose or any event considered drug-related by the investigator through the end of the study.

AE: any unfavorable and unintended sign, symptom, or disease temporally associated with use of medicinal product, whether or not it is considered related to medicinal product. TEAE: any AE (serious/non-serious) with onset or worsening of a pre-existing condition on or after the first administration of study drug through 30 days following last dose or any event considered drug-related by investigator through end of study. As per NCI-CTCAE version 4.03, Grade 1: asymptomatic or mild symptoms, clinical or diagnostic observations only, intervention not indicated; Grade 2: moderate, minimal, local or noninvasive intervention indicated, limiting age-appropriate instrumental activities of daily life (ADL); Grade 3: severe or medically significant but not immediately life-threatening, hospitalization or prolongation of existing hospitalization indicated, disabling, limiting self-care ADL; Grade 4: life-threatening consequence, urgent intervention indicated; Grade 5: death related to AE.

EORTC QLQC30: Disease specific indication that rates overall QoL in cancer participants. It consists of 30 general questions from 3 domains; 1) global health status, 2) functioning scales (physical, emotional, cognitive, social and role functioning), 3) symptom scales (fatigue, nausea, vomiting, pain, dyspnoea, insomnia, appetite loss, constipation, diarrhea, financial difficulty). Out of 30 questions, 28 questions were scored using scale of 1 to 4, represented answers of 'not at all', 'a little', 'quite a bit', and 'very much'; remaining 2 questions contributed to global health status were scored on scale of 1 to 7, represented range of 'very poor' to 'excellent' that evaluated overall health and QoL. All scales and single-item measures range from 0 to 100, where higher score represented higher response level. Higher score for functional scale, global health status and symptom scale represented high level of functioning, high QoL, and high level of symptoms or problems, respectively.

Clinically significant laboratory tests abnormalities were analyzed and reported for this outcome measure.

Karyopharm Therapeutics Inc

Analysis was performed on safety population that included all participants who had received any amount of study medication.

Participants with ovarian carcinoma who were platinum refractory or platinum resistant and had received at least one line of chemotherapy for relapsed disease received a dose of 50 mg/m\^2 of selinexor oral tablets BIW (doses at least 36 hours apart) with light meal and 120 mL of water in a 4-week treatment cycles. After 12 weeks of treatment, a dose of 60 mg/m\^2 of selinexor oral tablets BIW were administrated if the participants had no major toxicity. During dose reduction, participants received a minimum dose of 35 mg/m\^2 QW. This treatment continued until PD or unacceptable toxicity or any discontinuation criteria or withdrawal of consent by the participant, or non-compliance by the participant with protocol requirements.

Part 1: Cohort A-Ovarian Carcinoma: Selinexor up to 60 mg/m^2 BIW

Part 1: Cohort B-Endometrial Carcinoma: Selinexor up to 60 mg/m^2 BIW

Part 1: Cohort C-Cervical Carcinoma: Selinexor up to 60 mg/m^2 BIW

Part 2: Cohort A-Ovarian Carcinoma Schedule 1: Selinexor up to 50 mg/m^2 BIW

Part 2: Cohort A-Ovarian Carcinoma Schedule 2: Selinexor up to 60 mg/m^2 QW

Total

Age, Categorical

Sex: Female, Male

Ethnicity (NIH/OMB)

Race

Race/Ethnicity, Customized

Baseline analysis was performed on safety population that included all participants who had received any amount of study drug.

Jatin Shah, MD

Analysis was performed on modified intent-to-treat (mITT) population that included all participants who received at least 1 dose of study drug, had measurable disease per RECIST at baseline, and had at least 1 post-baseline efficacy follow-up information.

Percentage of Participants With Disease Control Response According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)

Analysis was performed on mITT population that included all participants who received at least 1 dose of study drug, had measurable disease per RECIST at baseline, and had at least 1 post-baseline efficacy follow-up information.

Percentage of Participants With Overall Response According to RECIST v1.1

Analysis was performed on GCIG evaluable population that included all participants in the ovarian cancer cohort (Cohort A) who had received at least 1 dose of study drug, had measurable disease per RECIST at baseline or baseline CA-125 assessment, and had at least 1 post-baseline efficacy follow-up information (i.e., either post-baseline scan or CA-125 assessment). Data for this outcome measure was not planned to be collected and analyzed for Cohort B and Cohort C, as pre-specified in protocol.

Percentage of Participants With Disease Control According to Gynecological Cancer Intergroup (GCIG) Response Criteria

Analysis was performed on GCIG evaluable population that included all participants in the ovarian cancer cohort (Cohort A) who had received at least 1 dose of study drug, had measurable disease per RECIST at baseline or baseline CA-125 assessment, and had at least 1 post-baseline efficacy follow-up information (i.e., either post-baseline scan or CA-125 assessment). Data for this outcome measure were not planned to be collected and analyzed for Cohort B and Cohort C, as pre-specified in protocol.

Percentage of Participants With Overall Response According to GCIG Response Criteria

Progression-free Survival (PFS) According to RECIST v1.1

Overall Survival (OS)

12 months

24 months

Percentage of Participants Who Survived at 12 and 24 Months

Participants with TEAE

Participants with TESAE

Analysis was performed on safety population that included all participants who had received any amount of study drug.

Number of Participants With Treatment-emergent Adverse Events (TEAE) and Treatment-emergent Serious Adverse Events (TESAE) According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 4.03

Number of Participants With Treatment-emergent Adverse Events by Severity According to National Cancer Institute Common Terminology Criteria for Adverse Events NCI CTCAE, Version 4.03

Global Health Status/ QoL: Baseline

Global Health Status/ QoL: EOT

Functioning Scales/ Physical Functioning: Baseline

Functioning Scales/ Physical Functioning: EOT

Functioning Scales/ Role Functioning: Baseline

Functioning Scales/ Role Functioning: EOT

Functioning Scales/ Emotional Functioning: Baseline

Functioning Scales/ Emotional Functioning: EOT

Functioning Scales/ Cognitive Functioning: Baseline

Functioning Scales/ Cognitive Functioning: EOT

Functioning Scales/ Social Functioning: Baseline

Functioning Scales/ Social Functioning: EOT

Symptom Scales/Items/ Fatigue: Baseline

Symptom Scales/Items/ Fatigue: EOT

Symptom Scales/Items/ Nausea And Vomiting: Baseline

Symptom Scales/Items/ Nausea And Vomiting: EOT

Symptom Scales/Items/ Pain: Baseline

Symptom Scales/Items/ Pain: EOT

Symptom Scales/Items/ Dyspnoea: Baseline

Symptom Scales/Items/ Dyspnoea: EOT

Symptom Scales/Items/ Insomnia: Baseline

Symptom Scales/Items/ Insomnia: EOT

Symptom Scales/Items/ Appetite Loss: Baseline

Symptom Scales/Items/ Appetite Loss: EOT

Symptom Scales/Items/ Constipation: Baseline

Symptom Scales/Items/ Constipation: EOT

Symptom Scales/Items/ Diarrhoea: Baseline

Symptom Scales/Items/ Diarrhoea: EOT

Symptom Scales/Items/ Financial Difficulties: Baseline

Symptom Scales/Items/ Financial Difficulties: EOT

Analysis was performed on mITT population that included all participants who received at least 1 dose of study drug, had measurable disease per RECIST at baseline, and had at least 1 post-baseline efficacy follow-up information. Here, 'Overall number of participants analyzed' signifies participants with available data for the outcome measure and "Number analyzed' signifies number of participants with available data for specified categories.

Quality of Life (QoL): Change From Baseline European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQC30) Scores

Spots Global Cancer Trial Database for Study of KPT-330 (Selinexor) in Female Patients With Advanced Gynaecologic Malignancies

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

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