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| ID | Type | Description | Link |
|---|---|---|---|
| 2013-003650-24 | EudraCT Number |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
|
| 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. |
|
| 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. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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) |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Participants With Overall Response According to RECIST v1.1 | 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. |
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Inclusion Criteria:
Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
Adequate hematologic function defined as:
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).
The participant has recovered to Grade less than or equal to (≤) 1 by the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.03 (NCI-CTCAE v4.03) from the effects of recent surgery, radiotherapy, chemotherapy, hormonal therapy, or other targeted therapies, with the exception of alopecia. The exceptions for such effects are allowed lab values of ≤Grade 2 specified elsewhere in these inclusion criteria.
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.
Ovarian, fallopian tube, or peritoneal carcinoma: both platinum refractory* and platinum resistant** participants, who have received ≥1 line of chemotherapy for relapsed disease (i.e., ≥2 lines of chemotherapy in total).
*Platinum refractory is defined as progression during or within 4 weeks of last treatment with a platinum-containing therapy.
**Platinum resistant is defined as relapse 4 weeks to <6 months after a platinum-containing therapy.
Endometrial carcinoma: participants must have received ≥1 line of chemotherapy for relapsed or advanced (Stage IV, IIIc) disease.
Cervical carcinoma: participants must have received ≥1 line of chemotherapy for relapsed or advanced (Stage IV b) disease.
Carcinosarcomas (Malignant Mixed Mullerian Tumor) are allowed, but all other nonepithelial cancers of the ovary, fallopian tube, endometrium, or cervix are excluded.
Participants must have either measurable disease per RECIST 1.1 or evaluable disease outside irradiated field on CT/MRI. For ovarian cancer: Participants must have disease that is measurable according to RECIST or assessable according to the Gynecological Cancer Intergroup (GCIG) CA-125 criterion. A rise in CA-125 or other tumor marker alone is not sufficient.
Exclusion Criteria:
Disease-Specific Exclusions:
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:
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.
All non-epithelial cancers of the ovary, fallopian tube, peritoneum, endometrium or cervix as well as neuro-endocrine tumors are excluded.
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| UZ Leuven - Universitair Ziekenhuis Leuven | Leuven | B-3000 | Belgium | |||
| Aalborg University Hospital |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 31822399 | Derived | 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. |
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A total of 116 participants were enrolled out of which 2 participants discontinued the study before the start of the treatment (1 participant due to death and 1 participant due to other reason). Total 114 participants started the study treatment.
The study was conducted between 09-April-2014 and 29-Mar-2017.
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| ID | Title | Description |
|---|---|---|
| FG000 | Part 1: Cohort A-Ovarian Carcinoma: Selinexor up to 60 mg/m^2 BIW | 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. |
| FG001 | Part 1: Cohort B-Endometrial Carcinoma: Selinexor up to 60 mg/m^2 BIW | 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. |
| FG002 | Part 1: Cohort C-Cervical Carcinoma: Selinexor up to 60 mg/m^2 BIW | 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. |
| FG003 | Part 2: Cohort A-Ovarian Carcinoma Schedule 1: Selinexor up to 50 mg/m^2 BIWmg/m^2 | 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. |
| FG004 | Part 2: Cohort A-Ovarian Carcinoma Schedule 2: Selinexor up to 60 mg/m^2 QW | 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. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Baseline analysis was performed on safety population that included all participants who had received any amount of study drug.
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| ID | Title | Description |
|---|---|---|
| BG000 | Part 1: Cohort A-Ovarian Carcinoma: Selinexor up to 60 mg/m^2 BIW | 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. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | 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. | Posted | Number | 95% Confidence Interval | percentage of participants | Baseline up to 30 days after last dose administration, assessed after 6 weeks and 12 weeks (approximately 35 months) |
From start of study treatment up to 30 days after last dose administration (approximately 35 months)
Analysis was performed on safety population that included all participants who had received any amount of study medication.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Part 1: Cohort A-Ovarian Carcinoma: Selinexor up to 60 mg/m^2 BIW | 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. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Vomiting | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Nausea | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Jatin Shah, MD | Karyopharm Therapeutics Inc. | (617) 658-0600 | jshah@karyopharm.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Aug 4, 2016 | Dec 4, 2020 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Jul 24, 2017 | Dec 4, 2020 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D010051 | Ovarian Neoplasms |
| D016889 | Endometrial Neoplasms |
| D002583 | Uterine Cervical Neoplasms |
| ID | Term |
|---|---|
| D004701 | Endocrine Gland Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D010049 | Ovarian Diseases |
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| ID | Term |
|---|---|
| C585161 | selinexor |
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|
| 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. |
|
| 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. |
|
|
| 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 | 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). | 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 | 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). | Baseline up to the date of progression or recurrence (approximately 35 months) |
| Progression-free Survival (PFS) According to RECIST v1.1 | 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. | From start of study drug administration until PD or discontinuation from the study or death, whichever occurred first (approximately 35 months) |
| Overall Survival (OS) | 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. | From start of study treatment up to the date of death, assessed every 3 months (approximately 35 months) |
| Percentage of Participants Who Survived at 12 and 24 Months | 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. | 12 and 24 months |
| 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 | 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. | From start of study treatment up to 30 days after the last dose administration (approximately 35 months) |
| 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 | 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. | From start of study treatment up to 30 days after the last dose administration (approximately 35 months) |
| Quality of Life (QoL): Change From Baseline European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQC30) Scores | 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. | Baseline, End of treatment (EOT) i.e., 30 days after last dose of study drug administration (up to 31 months) |
| Number of Participants With Individual Clinically Significant Abnormalities in Laboratory Tests | Clinically significant laboratory tests abnormalities were analyzed and reported for this outcome measure. | From start of study treatment up to 30 days after the last dose administration (approximately 35 months) |
| Aalborg |
| DK-9100 |
| Denmark |
| Rigshospitalet | Copenhagen | DK-2100 | Denmark |
| Herlev Hospital | Herlev | DK-2730 | Denmark |
| Termination of study by Sponsor |
|
| Death |
|
| BG001 | Part 1: Cohort B-Endometrial Carcinoma: Selinexor up to 60 mg/m^2 BIW | 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. |
| BG002 | Part 1: Cohort C-Cervical Carcinoma: Selinexor up to 60 mg/m^2 BIW | 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. |
| BG003 | Part 2: Cohort A-Ovarian Carcinoma Schedule 1: Selinexor up to 50 mg/m^2 BIW | 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. |
| BG004 | Part 2: Cohort A-Ovarian Carcinoma Schedule 2: Selinexor up to 60 mg/m^2 QW | 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. |
| BG005 | Total | Total of all reporting groups |
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Count of Participants | Participants |
|
|
|
|
| Secondary | Percentage of Participants With Overall Response According to RECIST v1.1 | 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. | 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. | Posted | Number | 95% Confidence Interval | percentage of participants | Baseline up to the date of progression or recurrence (approximately 35 months) |
|
|
|
| Secondary | Percentage of Participants With Disease Control According to Gynecological Cancer Intergroup (GCIG) Response Criteria | 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). | 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. | Posted | Number | 95% Confidence Interval | percentage of participants | Baseline up to 30 days after last dose administration, assessed after 6 weeks and 12 weeks (approximately 35 months) |
|
|
|
| Secondary | Percentage of Participants With Overall Response According to GCIG Response Criteria | 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). | 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. | Posted | Number | 95% Confidence Interval | percentage of participants | Baseline up to the date of progression or recurrence (approximately 35 months) |
|
|
|
| Secondary | Progression-free Survival (PFS) According to RECIST v1.1 | 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. | 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. | Posted | Median | 95% Confidence Interval | days | From start of study drug administration until PD or discontinuation from the study or death, whichever occurred first (approximately 35 months) |
|
|
|
| Secondary | Overall Survival (OS) | 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. | 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. | Posted | Median | 95% Confidence Interval | days | From start of study treatment up to the date of death, assessed every 3 months (approximately 35 months) |
|
|
|
| Secondary | Percentage of Participants Who Survived at 12 and 24 Months | 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. | 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. | Posted | Number | 95% Confidence Interval | percentage of participants | 12 and 24 months |
|
|
|
| Secondary | 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 | 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. | Analysis was performed on safety population that included all participants who had received any amount of study drug. | Posted | Count of Participants | Participants | From start of study treatment up to 30 days after the last dose administration (approximately 35 months) |
|
|
|
| Secondary | 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 | 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. | Analysis was performed on safety population that included all participants who had received any amount of study drug. | Posted | Count of Participants | Participants | From start of study treatment up to 30 days after the last dose administration (approximately 35 months) |
|
|
|
| Secondary | Quality of Life (QoL): Change From Baseline European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQC30) Scores | 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. | 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. | Posted | Mean | Standard Deviation | scores on a scale | Baseline, End of treatment (EOT) i.e., 30 days after last dose of study drug administration (up to 31 months) |
|
|
|
| Secondary | Number of Participants With Individual Clinically Significant Abnormalities in Laboratory Tests | Clinically significant laboratory tests abnormalities were analyzed and reported for this outcome measure. | Analysis was performed on safety population that included all participants who had received any amount of study drug. | Posted | Count of Participants | Participants | From start of study treatment up to 30 days after the last dose administration (approximately 35 months) |
|
|
|
| 21 |
| 25 |
| 14 |
| 25 |
| 25 |
| 25 |
| EG001 | Part 1: Cohort B-Endometrial Carcinoma: Selinexor up to 60 mg/m^2 BIW | 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. | 20 | 23 | 14 | 23 | 23 | 23 |
| EG002 | Part 1: Cohort C-Cervical Carcinoma: Selinexor up to 60 mg/m^2 BIW | 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. | 23 | 25 | 6 | 25 | 25 | 25 |
| EG003 | Part 2: Cohort A-Ovarian Carcinoma Schedule 1: Selinexor up to 50 mg/m^2 BIW | 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. | 20 | 21 | 12 | 21 | 21 | 21 |
| EG004 | Part 2: Cohort A-Ovarian Carcinoma Schedule 2: Selinexor up to 60 mg/m^2 QW | 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. | 17 | 20 | 12 | 20 | 20 | 20 |
| Ascites | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Ileus | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Anal Haemorrhage | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Haematemesis | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Rectal Haemorrhage | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Abdominal Pain | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Gastrointestinal Disorder | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Intestinal Obstruction | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Obstruction Gastric | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Small Intestinal Obstruction | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Dehydration | Metabolism and nutrition disorders | MedDRA 20.1 | Systematic Assessment |
|
| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA 20.1 | Systematic Assessment |
|
| Decreased Appetite | Metabolism and nutrition disorders | MedDRA 20.1 | Systematic Assessment |
|
| Hyponatraemia | Metabolism and nutrition disorders | MedDRA 20.1 | Systematic Assessment |
|
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA 20.1 | Systematic Assessment |
|
| Bacteraemia | Infections and infestations | MedDRA 20.1 | Systematic Assessment |
|
| Lung Infection | Infections and infestations | MedDRA 20.1 | Systematic Assessment |
|
| Pneumonia | Infections and infestations | MedDRA 20.1 | Systematic Assessment |
|
| Urosepsis | Infections and infestations | MedDRA 20.1 | Systematic Assessment |
|
| Varicella Zoster Virus Infection | Infections and infestations | MedDRA 20.1 | Systematic Assessment |
|
| Escherichia Infection | Infections and infestations | MedDRA 20.1 | Systematic Assessment |
|
| Peritonitis | Infections and infestations | MedDRA 20.1 | Systematic Assessment |
|
| Respiratory Tract Infection | Infections and infestations | MedDRA 20.1 | Systematic Assessment |
|
| Urinary Tract Infection | Infections and infestations | MedDRA 20.1 | Systematic Assessment |
|
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Pleural Effusion | Respiratory, thoracic and mediastinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Pneumothorax | Respiratory, thoracic and mediastinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Pulmonary Embolism | Respiratory, thoracic and mediastinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Pyrexia | General disorders | MedDRA 20.1 | Systematic Assessment |
|
| Gait Disturbance | General disorders | MedDRA 20.1 | Systematic Assessment |
|
| Malaise | General disorders | MedDRA 20.1 | Systematic Assessment |
|
| Discomfort | General disorders | MedDRA 20.1 | Systematic Assessment |
|
| General Physical Health Deterioration | General disorders | MedDRA 20.1 | Systematic Assessment |
|
| Inflammation | General disorders | MedDRA 20.1 | Systematic Assessment |
|
| Acute Kidney Injury | Renal and urinary disorders | MedDRA 20.1 | Systematic Assessment |
|
| Cystitis Noninfective | Renal and urinary disorders | MedDRA 20.1 | Systematic Assessment |
|
| Renal Failure | Renal and urinary disorders | MedDRA 20.1 | Systematic Assessment |
|
| Urinary Retention | Renal and urinary disorders | MedDRA 20.1 | Systematic Assessment |
|
| Anaemia | Blood and lymphatic system disorders | MedDRA 20.1 | Systematic Assessment |
|
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA 20.1 | Systematic Assessment |
|
| Deep Vein Thrombosis | Vascular disorders | MedDRA 20.1 | Systematic Assessment |
|
| Embolism | Vascular disorders | MedDRA 20.1 | Systematic Assessment |
|
| Cataract | Eye disorders | MedDRA 20.1 | Systematic Assessment |
|
| Vision Blurred | Eye disorders | MedDRA 20.1 | Systematic Assessment |
|
| Supraventricular Tachycardia | Cardiac disorders | MedDRA 20.1 | Systematic Assessment |
|
| Femoral Neck Fracture | Injury, poisoning and procedural complications | MedDRA 20.1 | Systematic Assessment |
|
| Back Pain | Musculoskeletal and connective tissue disorders | MedDRA 20.1 | Systematic Assessment |
|
| Intracranial Tumour Haemorrhage | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 20.1 | Systematic Assessment |
|
| Aphasia | Nervous system disorders | MedDRA 20.1 | Systematic Assessment |
|
| Cognitive Disorder | Nervous system disorders | MedDRA 20.1 | Systematic Assessment |
|
| Drain Placement | Surgical and medical procedures | MedDRA 20.1 | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Abdominal Pain | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Abdominal Distension | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Stomatitis | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Ascites | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Dry Mouth | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Abdominal Pain Upper | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Abdominal Pain Lower | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Dyspepsia | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Abdominal Discomfort | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Defaecation Urgency | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Gastrooesophageal Reflux Disease | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Intestinal Obstruction | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Mouth Ulceration | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Oesophageal Irritation | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Oesophageal Pain | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Oral Mucosal Blistering | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Fatigue | General disorders | MedDRA 20.1 | Systematic Assessment |
|
| Asthenia | General disorders | MedDRA 20.1 | Systematic Assessment |
|
| Malaise | General disorders | MedDRA 20.1 | Systematic Assessment |
|
| Pyrexia | General disorders | MedDRA 20.1 | Systematic Assessment |
|
| Oedema Peripheral | General disorders | MedDRA 20.1 | Systematic Assessment |
|
| Face Oedema | General disorders | MedDRA 20.1 | Systematic Assessment |
|
| General Physical Health Deterioration | General disorders | MedDRA 20.1 | Systematic Assessment |
|
| Oedema | General disorders | MedDRA 20.1 | Systematic Assessment |
|
| Chills | General disorders | MedDRA 20.1 | Systematic Assessment |
|
| Decreased Appetite | Metabolism and nutrition disorders | MedDRA 20.1 | Systematic Assessment |
|
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA 20.1 | Systematic Assessment |
|
| Hypomagnesaemia | Metabolism and nutrition disorders | MedDRA 20.1 | Systematic Assessment |
|
| Hyponatraemia | Metabolism and nutrition disorders | MedDRA 20.1 | Systematic Assessment |
|
| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA 20.1 | Systematic Assessment |
|
| Dehydration | Metabolism and nutrition disorders | MedDRA 20.1 | Systematic Assessment |
|
| Hyperkalaemia | Metabolism and nutrition disorders | MedDRA 20.1 | Systematic Assessment |
|
| Hypoalbuminaemia | Metabolism and nutrition disorders | MedDRA 20.1 | Systematic Assessment |
|
| Hypophosphataemia | Metabolism and nutrition disorders | MedDRA 20.1 | Systematic Assessment |
|
| Anaemia | Blood and lymphatic system disorders | MedDRA 20.1 | Systematic Assessment |
|
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA 20.1 | Systematic Assessment |
|
| Pancytopenia | Blood and lymphatic system disorders | MedDRA 20.1 | Systematic Assessment |
|
| Neutropenia | Blood and lymphatic system disorders | MedDRA 20.1 | Systematic Assessment |
|
| Dysgeusia | Nervous system disorders | MedDRA 20.1 | Systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA 20.1 | Systematic Assessment |
|
| Peripheral Sensory Neuropathy | Nervous system disorders | MedDRA 20.1 | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA 20.1 | Systematic Assessment |
|
| Paraesthesia | Nervous system disorders | MedDRA 20.1 | Systematic Assessment |
|
| Somnolence | Nervous system disorders | MedDRA 20.1 | Systematic Assessment |
|
| Syncope | Nervous system disorders | MedDRA 20.1 | Systematic Assessment |
|
| Aphasia | Nervous system disorders | MedDRA 20.1 | Systematic Assessment |
|
| Weight Decreased | Investigations | MedDRA 20.1 | Systematic Assessment |
|
| Urinary Tract Infection | Infections and infestations | MedDRA 20.1 | Systematic Assessment |
|
| Cystitis | Infections and infestations | MedDRA 20.1 | Systematic Assessment |
|
| Lung Infection | Infections and infestations | MedDRA 20.1 | Systematic Assessment |
|
| Nasopharyngitis | Infections and infestations | MedDRA 20.1 | Systematic Assessment |
|
| Laryngitis | Infections and infestations | MedDRA 20.1 | Systematic Assessment |
|
| Pneumonia | Infections and infestations | MedDRA 20.1 | Systematic Assessment |
|
| Bronchitis | Infections and infestations | MedDRA 20.1 | Systematic Assessment |
|
| Infection | Infections and infestations | MedDRA 20.1 | Systematic Assessment |
|
| Oral Candidiasis | Infections and infestations | MedDRA 20.1 | Systematic Assessment |
|
| Helicobacter Infection | Infections and infestations | MedDRA 20.1 | Systematic Assessment |
|
| Herpes Simplex | Infections and infestations | MedDRA 20.1 | Systematic Assessment |
|
| Peritonitis | Infections and infestations | MedDRA 20.1 | Systematic Assessment |
|
| Respiratory Tract Infection | Infections and infestations | MedDRA 20.1 | Systematic Assessment |
|
| Vision Blurred | Eye disorders | MedDRA 20.1 | Systematic Assessment |
|
| Visual Impairment | Eye disorders | MedDRA 20.1 | Systematic Assessment |
|
| Cataract | Eye disorders | MedDRA 20.1 | Systematic Assessment |
|
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Pulmonary Embolism | Respiratory, thoracic and mediastinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Pleural Effusion | Respiratory, thoracic and mediastinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Oropharyngeal Pain | Respiratory, thoracic and mediastinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Dyspnoea Exertional | Respiratory, thoracic and mediastinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Hiccups | Respiratory, thoracic and mediastinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Back Pain | Musculoskeletal and connective tissue disorders | MedDRA 20.1 | Systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 20.1 | Systematic Assessment |
|
| Muscular Weakness | Musculoskeletal and connective tissue disorders | MedDRA 20.1 | Systematic Assessment |
|
| Musculoskeletal Chest Pain | Musculoskeletal and connective tissue disorders | MedDRA 20.1 | Systematic Assessment |
|
| Pain In Extremity | Musculoskeletal and connective tissue disorders | MedDRA 20.1 | Systematic Assessment |
|
| Muscle Spasms | Musculoskeletal and connective tissue disorders | MedDRA 20.1 | Systematic Assessment |
|
| Musculoskeletal Pain | Musculoskeletal and connective tissue disorders | MedDRA 20.1 | Systematic Assessment |
|
| Osteoarthritis | Musculoskeletal and connective tissue disorders | MedDRA 20.1 | Systematic Assessment |
|
| Insomnia | Psychiatric disorders | MedDRA 20.1 | Systematic Assessment |
|
| Anxiety | Psychiatric disorders | MedDRA 20.1 | Systematic Assessment |
|
| Confusional State | Psychiatric disorders | MedDRA 20.1 | Systematic Assessment |
|
| Depression | Psychiatric disorders | MedDRA 20.1 | Systematic Assessment |
|
| Hallucination | Psychiatric disorders | MedDRA 20.1 | Systematic Assessment |
|
| Agitation | Psychiatric disorders | MedDRA 20.1 | Systematic Assessment |
|
| Dysuria | Renal and urinary disorders | MedDRA 20.1 | Systematic Assessment |
|
| Haematuria | Renal and urinary disorders | MedDRA 20.1 | Systematic Assessment |
|
| Pollakiuria | Renal and urinary disorders | MedDRA 20.1 | Systematic Assessment |
|
| Hydronephrosis | Renal and urinary disorders | MedDRA 20.1 | Systematic Assessment |
|
| Night Sweats | Skin and subcutaneous tissue disorders | MedDRA 20.1 | Systematic Assessment |
|
| Alopecia | Skin and subcutaneous tissue disorders | MedDRA 20.1 | Systematic Assessment |
|
| Skin Fissures | Skin and subcutaneous tissue disorders | MedDRA 20.1 | Systematic Assessment |
|
| Hypotension | Vascular disorders | MedDRA 20.1 | Systematic Assessment |
|
| Hot Flush | Vascular disorders | MedDRA 20.1 | Systematic Assessment |
|
| Deep Vein Thrombosis | Vascular disorders | MedDRA 20.1 | Systematic Assessment |
|
| Hypertension | Vascular disorders | MedDRA 20.1 | Systematic Assessment |
|
| Ear Discomfort | Ear and labyrinth disorders | MedDRA 20.1 | Systematic Assessment |
|
| Vertigo | Ear and labyrinth disorders | MedDRA 20.1 | Systematic Assessment |
|
| Auditory Disorder | Ear and labyrinth disorders | MedDRA 20.1 | Systematic Assessment |
|
| Contusion | Injury, poisoning and procedural complications | MedDRA 20.1 | Systematic Assessment |
|
| Humerus Fracture | Injury, poisoning and procedural complications | MedDRA 20.1 | Systematic Assessment |
|
| Procedural Pain | Injury, poisoning and procedural complications | MedDRA 20.1 | Systematic Assessment |
|
| Vaginal Haemorrhage | Reproductive system and breast disorders | MedDRA 20.1 | Systematic Assessment |
|
| Device Occlusion | Product Issues | MedDRA 20.1 | Systematic Assessment |
|
| Dry Eye | Eye disorders | MedDRA 20.1 | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Device Related Infection | Infections and infestations | MedDRA 20.1 | Systematic Assessment |
|
| Polyurea | Renal and urinary disorders | MedDRA 20.1 | Systematic Assessment |
|
Not provided
Not provided
| D000291 |
| Adnexal Diseases |
| D005831 | Genital Diseases, Female |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D005833 | Genital Neoplasms, Female |
| D014565 | Urogenital Neoplasms |
| D000091662 | Genital Diseases |
| D004700 | Endocrine System Diseases |
| D006058 | Gonadal Disorders |
| D014594 | Uterine Neoplasms |
| D014591 | Uterine Diseases |
| D002577 | Uterine Cervical Diseases |
| 24 months |
|
| Participants with TESAE |
|
| Moderate (Grade 2) |
|
| Severe (Grade 3) |
|
| Life threatening (Grade 4) |
|
| Fatal (Grade 5) |
|
|
| 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 |
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| Symptom Scales/Items/ Dyspnoea: Baseline |
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| Symptom Scales/Items/ Dyspnoea: EOT |
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| Symptom Scales/Items/ Insomnia: Baseline |
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| Symptom Scales/Items/ Insomnia: EOT |
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| Symptom Scales/Items/ Appetite Loss: Baseline |
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| Symptom Scales/Items/ Appetite Loss: EOT |
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| Symptom Scales/Items/ Constipation: Baseline |
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| Symptom Scales/Items/ Constipation: EOT |
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| Symptom Scales/Items/ Diarrhoea: Baseline |
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| Symptom Scales/Items/ Diarrhoea: EOT |
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| Symptom Scales/Items/ Financial Difficulties: Baseline |
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| Symptom Scales/Items/ Financial Difficulties: EOT |
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