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

NCT02025985 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: KCP-330-0052013-003650-24
• Study Type: interventional
• Target: 116
• Locations: 2 countries
• Sites: 4

Brief Summary

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.

Conditions

Ovarian Carcinoma; Endometrial Carcinoma; Cervical Carcinoma

Keywords

Karyopharm; KPT-330; Selinexor; SIGN; ovarian cancer; endometrial cancer; cervical cancer; SINE™; HER2 negative

Outcome Measures

Primary Outcomes (1)

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

  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.

  Baseline up to 30 days after last dose administration, assessed after 6 weeks and 12 weeks (approximately 35 months)

Secondary Outcomes (10)

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

  Baseline up to the date of progression or recurrence (approximately 35 months)

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

  Baseline up to 30 days after last dose administration, assessed after 6 weeks and 12 weeks (approximately 35 months)

• Percentage of Participants With Overall Response According to GCIG Response Criteria

  Baseline up to the date of progression or recurrence (approximately 35 months)

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

  From start of study drug administration until PD or discontinuation from the study or death, whichever occurred first (approximately 35 months)

• Overall Survival (OS)

  From start of study treatment up to the date of death, assessed every 3 months (approximately 35 months)

Study Arms (5)

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

EXPERIMENTAL

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.

Drug: Selinexor

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

EXPERIMENTAL

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.

Drug: Selinexor

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

EXPERIMENTAL

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.

Drug: Selinexor

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

EXPERIMENTAL

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.

Drug: Selinexor

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

EXPERIMENTAL

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.

Drug: Selinexor

Interventions

Selinexor DRUG

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.

Also known as: KPT-330, XPOVIO

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

Eligibility Criteria

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

You may qualify if:

• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
• Adequate hematologic function defined as:
• platelets ≥125\*10\^9 per liter (/L)
• hemoglobin ≥5.59 millimoles per liter (mmol/L) or 9 grams per deciliter (g/dL)
• Absolute neutrophil count (ANC) ≥1.5\*10\^9/L
• White blood cells (WBC) count ≥3.0\*10\^9/L
• Up to 5 percent (%) deviation is tolerated. Transfusions and growth factors are allowed.
• Adequate liver function defined as adequate hepatic function within 14 days prior to Cycle 1 Day 1: total bilirubin \<2 times the upper limit of normal (ULN) (except participants with Gilbert's syndrome, who must have a total bilirubin of \<3 times ULN), aspartate aminotransferase (AST) \<2.0 times ULN, and alanine aminotransferase (ALT) \<2.0 times ULN. In the case of known (radiologically and/or biopsy- documented) liver metastasis, AST \<5.0 times ULN and ALT \<5.0 times ULN is acceptable. Up to 10% deviation is acceptable.
• Renal function defined as a calculated or measured glomerular filtration rate ≥30 milliliter per minute (mL/min).
• Life expectancy of at least 12 weeks.
• Able to swallow and retain oral medication.
• Participants must give informed consent according to the rules and regulations of the individual participating sites.
• Negative serum pregnancy test in women of childbearing potential within 14 days of first dose of treatment, and participants of childbearing potential must agree to use effective contraception during treatment up to 3 months from last dose. Fertile male partners must be willing and able to use effective non-hormonal means of contraception (barrier method of contraception in conjunction with spermicidal jelly, or surgical sterilization) during and for at least 6 months post-study treatment.
• The participant must be recovered from any prior treatment/major operation. The treatment/major operation must be performed at least 4 weeks prior to start of study drug. Palliative radiotherapy is permitted until one week prior to the start of study drug.
• Only incurable participants with histologically or cytologically proven primary tumor and objective documentation of disease progression on prior treatment by computerized tomography (CT)/ magnetic resonance imaging (MRI) may be enrolled.

You may not qualify if:

• Evidence of complete or partial bowel obstruction.
• Need of Total Parenteral Nutrition.
• Participants who are pregnant or breast feeding.
• Radiation (except planned or on-going palliative radiation to bone outside of the region of measurable disease) ≤3 weeks prior to Cycle 1 Day 1.
• Chemotherapy, endocrine therapy, immunotherapy or any other systemic anti-cancer therapy (including investigational anti-cancer therapy) ≤3 weeks prior to Cycle 1 Day 1.
• Diagnosis or recurrence of invasive cancer other than the present cancer within 3 years (except basal or squamous cell carcinoma of the skin that has been definitively treated).
• Unstable cardiovascular function:
• Symptomatic ischemia, or
• Uncontrolled clinically significant conduction abnormalities (e.g. ventricular tachycardia on anti-arrhythmics are excluded and 1st degree atrioventricular (AV) block or asymptomatic left anterior fascicular block (LAFB)/ right bundle branch block (RBBB) will not be excluded), or
• Congestive heart failure (CHF) of New York Heart Association (NYHA) Class ≥3, or myocardial infarction (MI) within 3 months of Cycle 1 Day 1.
• Uncontrolled active infection requiring parenteral antibiotics, antivirals, or antifungals within one week prior to the first dose. Active infection with concurrent treatment is acceptable only if the participant is clinically stable.
• Significantly diseased or obstructed gastrointestinal tract or uncontrolled vomiting or diarrhea.
• Concurrent therapy with approved or investigational anti-cancer therapeutics.
• Medical, psychological, or social conditions that may interfere with the participant's participation in the study or evaluation of the study results.
• Known brain metastases unless adequately treated (surgery or radiotherapy) with no evidence of progression and neurologically stable off anticonvulsants and glucocorticoids.

Sponsors & Collaborators

• Karyopharm Therapeutics Inc: lead

Study Sites (4)

UZ Leuven - Universitair Ziekenhuis Leuven

Leuven, B-3000, Belgium

Location

Aalborg University Hospital

Aalborg, DK-9100, Denmark

Location

Rigshospitalet

Copenhagen, DK-2100, Denmark

Location

Herlev Hospital

Herlev, DK-2730, Denmark

Location

Related Publications (1)

• Vergote IB, Lund B, Peen U, Umajuridze Z, Mau-Sorensen M, Kranich A, Van Nieuwenhuysen E, Haslund C, Nottrup T, Han SN, Concin N, Unger TJ, Chai Y, Au N, Rashal T, Joshi A, Crochiere M, Landesman Y, Shah J, Shacham S, Kauffman M, Mirza MR. Phase 2 study of the Exportin 1 inhibitor selinexor in patients with recurrent gynecological malignancies. Gynecol Oncol. 2020 Feb;156(2):308-314. doi: 10.1016/j.ygyno.2019.11.012. Epub 2019 Dec 9.

  PMID: 31822399 DERIVED

MeSH Terms

Conditions

Ovarian Neoplasms; Endometrial Neoplasms; Uterine Cervical Neoplasms

Interventions

selinexor

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Uterine Neoplasms; Uterine Diseases; Uterine Cervical Diseases

Results Point of Contact

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

jshah@karyopharm.com

(617) 658-0600

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 27, 2013
• First Posted: January 1, 2014
• Study Start: April 9, 2014
• Primary Completion: January 24, 2017
• Study Completion: March 29, 2017
• Last Updated: January 26, 2023
• Results First Posted: February 2, 2021

Record last verified: 2023-01

Locations

BE (1); DK (3)