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| ID | Type | Description | Link |
|---|---|---|---|
| 2021-000080-67 | EudraCT Number |
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Upon further consideration of the existing data and the competitive landscape, Karyopharm Therapeutics Inc has decided not to pursue the ongoing development of Selinexor in GBM at this time.
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This is a Phase 1/2 study of selinexor in combination with standard of care (SoC) therapy for newly diagnosed glioblastoma (nGBM) or recurrent glioblastoma (rGBM). This study will be conducted in 2 phases: a Phase 1a dose finding study followed by Phase 1b (dose expansion) and a Phase 2 randomized efficacy exploration study and will independently evaluate 3 different combination regimens in 3 treatment arms in patients with nGBM (Arms A and B) or with rGBM (Arm C).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Phase 1: Arm A: Selinexor+Radiation Therapy | Experimental | Participants with nGBM uMGMT will receive 60 to 80 milligram (mg) of selinexor oral tablet once weekly (QW) across dose level -1, 1, 2, and 3 in combination with 2 Gray (Gy) radiation therapy (RT) daily for 5 days per week in a 42-day cycle during Cycle 1 radiation period followed by 80 mg of selinexor oral tablet on Day 1 and 15 in a 28-day Cycle 2 and subsequently will continue at 80 mg QW until progressive disease (PD) during adjuvant therapy period. |
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| Arm A Control: Temozolomide+Radiation Therapy | Active Comparator | Participants with nGBM uMGMT will receive 75 milligram per meter square (mg/m^2) of temozolomide oral capsule once daily (QD) in combination with 2 Gy RT daily for 5 days per week in a 42-day cycle during Cycle 1 radiation period followed by 150 mg/m^2 (started from Cycle 3) and increase to 200 mg/m^2 as tolerated per Investigator's judgment, daily for 5 days in a 28-day cycle during Cycles 4 to 8 cycles during adjuvant therapy period. |
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| Phase 1: Arm B: Selinexor+Temozolomide+Radiation Therapy | Experimental | Participants with nGBM mMGMT will receive 40-80 mg of selinexor oral tablet QW across dose level -1, 1, 2, 2a, 2b and 3a and 75 mg/m^2 of temozolomide oral capsule QD in combination with 2 Gy RT daily for 5 days per week in a 42-day cycle during Cycle 1 radiation period followed by 60 mg (dose level 2a) or 80 mg (dose level 2b and 3a) of selinexor oral tablet on Day 1 and 15 in a 28-day Cycle 2, followed by 150 mg/m^2 (started from Cycle 3) and increase to 200 mg/m^2 as tolerated per Investigator's judgment, daily for 5 days in a 28-day cycle during Cycle 4 to 8 during adjuvant therapy period. Participants will continue selinexor weekly per dose level assigned until PD. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Selinexor | Drug | Dose and Formulation: 20 milligram (mg); Tablet Route of Administration: Oral |
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| Measure | Description | Time Frame |
|---|---|---|
| Phase 1a and 1b: Maximum Tolerated Dose of Selinexor | MTD was defined as highest dose of selinexor in at which no more than one of six participants experienced a dose-limiting toxicity (DLT). DLT was based on Common Terminology Criteria for Adverse Events (CTCAE) v5.0. | At Cycle 1 (up to 42 days) |
| Phase 1a and 1b: Recommended Phase 2 Dose (RP2D) of Selinexor | The RP2D was determined by SRC, based on the MTD and the totality of efficacy and safety data of Phase 1a dose escalation study. RP2D was determined based on the totality of the available safety, efficacy, pharmacokinetic/pharmacodynamic (PK/PD). | From Cycle 1 Day 1 up to 14 days after last dose (up to 15.41 months) (Each Cycle length = up to 42 days) |
| Phase 1a and 1b: Number of Participants With Treatment-emergent Adverse Events (TEAEs) With Grade Greater Than or Equal to (>=) 3, Serious TEAEs and Who Discontinued Treatment Due to TEAEs | TEAE: any event that was not present prior to initiation of study treatment or any event already present that worsened in either intensity or frequency following exposure to study treatment. Serious adverse event (SAE): any untoward medical occurrence that, at any dose, resulted in death; was life threatening (i.e., an event in which participant was at risk of death at the time of the event; it did not refer to an event that hypothetically might have caused death if it were more severe); required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; or was a congenital anomaly/birth defect. Important medical events that might not result in death, was life-threatening, or require hospitalization might be considered serious when, based upon appropriate medical judgment, they might jeopardize participant and might require medical or surgical intervention to prevent one of the outcomes listed above. | From first dose of study treatment up to 30 days post last dose (Up to 16.41 months) |
| Phase 1a and 1b: Percentage of Participants With Progression Free Survival at 3 Months |
| Measure | Description | Time Frame |
|---|---|---|
| Phase 1a and 1b: Time to Progression (TTP) | TTP was defined for participants as the duration from start of treatment to the date of PD, or death due to PD, whichever occurs first. PD per RANO response criteria: 1) At least two sequential scans separated by at >=4 weeks both exhibiting >=25 percent (%) increase in sum of products of perpendicular diameters or >=40% increase in total volume of enhancing lesions. 2) In case where baseline or best response demonstrates no measurable enhancing disease, then any new measurable (>10mm*10mm) enhancing lesions considered PD after confirmed by a subsequent scan >=4 weeks exhibiting >=25% increase in sum of products of perpendicular diameters or >=40% increase in total volume of enhancing lesions relative to scan first illustrating new measurable disease. 3) Clear clinical deterioration not attributable to other causes apart from tumor or attributable to changes in steroid dose. 4) Failure to return for evaluation as a result of death or deteriorating condition. |
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Inclusion Criteria
Written informed consent in accordance with federal, local, and institutional guidelines.
Age ≥18 years at the time of informed consent and ≥22 year for Arm E.
Pathologically confirmed glioblastoma (including all histological variants; documentation to be provided) that are newly diagnosed (for Arms A and B) or relapsed disease (for Arm C, D and E) after 1 to 2 line of systemic therapy (RT ± TMZ or RT ± TMZ in combination with other drug) (surgical resection of recurrent disease allowed). For Arms A and B, MGMT status should be available.
Prior therapy:
Measurable disease according to RANO/modified RANO guidelines is required only for Arm C, D and E; it is not required for Arms A or B.
Participants enrolling into Arms C, D, and E must be on a stable or decreasing dose of corticosteroids (or none) for at least 5 days prior to the baseline magnetic resonance imaging (MRI).
Karnofsky Performance Score (KPS) ≥70 (for Arms A and B) and 60 (for Arms C, D, and E).
Participants must have adequate organ function ≤2 weeks of study treatment as defined by the following laboratory criteria:
Female participants of childbearing potential must have a negative serum pregnancy test at Screening and agree to use highly effective methods of contraception throughout the study and for 6 months following the last dose of study treatment.
Fertile male participants who are sexually active with a female of childbearing potential must use highly effective methods of contraception throughout the study and for 6 months following the last dose of study treatment.
For Arms A and B: participants must have had surgery and/or biopsy not greater than [>] 8 weeks prior to initial screening.
Participants must consent to provide tumor tissue and blood samples to be used for future molecular testing for correlative studies.
Limited to supratentorial disease for Arm E only.
Exclusion Criteria
- Participants who are receiving any other investigational agents and /or have had prior therapy including:
For Arms A and B only:
Participants who have previously received RT to the brain
Participants who received chemotherapy for the treatment of their glioma
Participants who are being treated with implanted Gliadel wafers
For Arm C:
Prior nitrosoureas
For Arms C, D, and E:
<4 weeks from prior TMZ or other chemotherapy, or <4 weeks or 5 half-lives (whichever is shorter) for investigational agents prior to start of study treatment
Prior treatment bevacizumab or other direct Vascular endothelial growth factor/Vascular endothelial growth factor receptor (VEGF/VEGFR) inhibitors. For any questions of the definition of a direct VEGF/VEGFR inhibitor, consult the study Medical Monitor
Any AE which has not recovered to Grade <=1, or returned to baseline, related to the previous GBM therapy, except alopecia, and some other Grade 2 AEs that have been stabilized (upon Medical Monitor approval)
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| Name | Affiliation | Role |
|---|---|---|
| Andrew B Lassman, MD | Columbia University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Alabama | Birmingham | Alabama | 35294 | United States | ||
| University of Southern California (USC Norris Comprehensive Cancer Center and LAC+USC Medical Center) |
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Due to the early study termination and pre-specified analysis, data was collected/reported according to disease characteristics and combined dose range (60 to 80 mg or 40 to 80 mg) participants received regardless of study phase. The 'per arm' or 'per dose level' data was not collected.
This study was conducted at 18 sites in the United States and Canada. This study had three phases: Phase 1a, Phase 1b and Phase 2. The study was early terminated during the Phase 1b portion of the study as the initial responses to selinexor treatment were not supportive of continued investigation in glioblastoma, therefore Phase 2 data could not be collected and there was no reporting of the Phase 2 data in this report.
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| ID | Title | Description |
|---|---|---|
| FG000 | Arm A: Selinexor + Radiation Therapy | Participants with newly diagnosed glioblastoma (nGBM) unmethylated O6-methylguanine-DNA-methyltransferase (uMGMT) received 60 to 80 milligrams (mg) of selinexor oral tablet, once weekly (QW) in combination with 2 Gray (Gy) radiation therapy (RT) daily for 5 days per week in a 42-day cycle during Cycle 1 radiation period followed by 80 mg of selinexor oral tablet on Day 1 and 15 in a 28-day Cycle 2 and subsequently continued at 80 mg of selinexor, QW until progressive disease (PD) during adjuvant therapy period. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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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 | May 11, 2021 | Jul 25, 2024 |
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| Arm B Control: Temozolomide+Radiation Therapy | Active Comparator | Participants with nGBM mMGMT will receive 75 mg/m^2 of temozolomide oral capsule QD in combination with 2 Gy RT daily for 5 days per week in a 42-day cycle during Cycle 1 radiation period followed by 150 mg/m^2 (started from Cycle 3) and increase to 200 mg/m^2 as tolerated per Investigator's judgment, daily for 5 days in a 28-day cycle during Cycles 4 to 8 during adjuvant therapy period. |
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| Arm C: Selinexor+Lomustine/Carmustine | Experimental | Participants with rGBM uMGMT or mMGMT will receive 40-80 mg of selinexor oral tablet QW across dose level -1, 1, 2, 2a, and 3 and 90-110 mg/m^2 of lomustine or 150-200 mg/m^2 of carmustine (substituted if lomustine is not available) capsule on Day 1 of each cycle across dose level -1, 1, 2, 2a, and 3 in a 42-day cycle for all cycles. |
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| Arm C Control: Lomustine/Carmustine | Active Comparator | Participants with rGBM uMGMT or mMGMT will receive 110 mg/m^2 of lomustine or 200 mg/m^2 of Carmustine (substituted if lomustine is not available) capsule on Day 1 of each cycle in a 42-day cycle for all cycles. |
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| Arm D: Selinexor+Bevacizumab | Experimental | Participants with rGBM will receive 60-80 mg of selinexor oral tablet QW across dose level -1, 1 and 10 mg/kg of Bevacizumab intravenous (IV) infusion every 2 weeks (Q2W) in 28-day cycle for all cycles. |
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| Arm E: Selinexor+TTField | Experimental | Participants with rGBM will receive 60-80 mg of selinexor oral tablet QW across dose level -1, 1 and will receive scalp application of 200 kilohertz (kHz) of transducer array ≥18 hours/day daily for each cycle in 28 day cycle for all cycles. |
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| Temozolomide (TMZ) | Drug | Dose strength and Formulation: 5, 20, 100, 140, 180, or 250 mg; Capsule Route of Administration: Oral |
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| Lomustine (CCNU) | Drug | Dose and Formulation: 10, 40, or 100 mg; Capsule Route of Administration: Oral |
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| Standard Fractionated Radiation therapy (RT) | Radiation | Radiation Therapy Oncology Group (RTOG) or European Organisation for Research and Treatment of Cancer (EORTC) methodologies of approximately 60 Gy in 30 fractions. |
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| Bevacizumab | Drug | Dose and Formulation: 10 mg/kg; Route of Administration: Intravenous |
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| TTField | Device | Dose and Formulation: 200 kHz ≥18h/day; Route of administration: Scalp application of transducer arrays. |
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| Carmustine | Drug | Dose and Formulation: 150 or 200 mg/m^2; Route of Administration: Intravenous |
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Progression defined as first occurrence of disease progression (PD) per modified Response Assessment in Neuro-Oncology (RANO) including both radiological PD and clinical deterioration. PD per RANO response criteria:1) At least two sequential scans separated by at >=4 weeks both exhibiting >=25 percent (%) increase in sum of products of perpendicular diameters or >=40% increase in total volume of enhancing lesions. 2) In case where baseline or best response demonstrates no measurable enhancing disease, then any new measurable (>10mm*10mm) enhancing lesions considered PD after confirmed by a subsequent scan >=4 weeks exhibiting >=25% increase in sum of products of perpendicular diameters or >=40% increase in total volume of enhancing lesions relative to scan first illustrating new measurable disease. 3) Clear clinical deterioration not attributable to other causes apart from tumor or attributable to changes in steroid dose. 4) Failure to return for evaluation as a result of death. |
| At 3 Months |
| Phase 1a and 1b: Overall Survival (OS) | OS was defined as the time from the date of randomization until death due to any cause or until lost to follow-up for all participants. | From date of randomization to the date of death due to any cause or until lost to follow-up (up to 20 months) |
| From first dose study treatment until progression or death due to progression (Up to 15.41 months) |
| Phase 1a and 1b: Progressive Free Survival (PFS) | Progression defined as first occurrence of PD per modified RANO including both radiological PD and clinical deterioration. PD per RANO response criteria: 1) At least two sequential scans separated by at >=4 weeks both exhibiting >=25 percent (%) increase in sum of products of perpendicular diameters or >=40% increase in total volume of enhancing lesions. 2) In case where baseline or best response demonstrates no measurable enhancing disease, then any new measurable (>10mm*10mm) enhancing lesions considered PD after confirmed by a subsequent scan >=4 weeks exhibiting >=25% increase in sum of products of perpendicular diameters or >=40% increase in total volume of enhancing lesions relative to scan first illustrating new measurable disease. 3) Clear clinical deterioration not attributable to other causes apart from tumor or attributable to changes in steroid dose. 4) Failure to return for evaluation as a result of death or deteriorating condition. | From first dose of study treatment until progression or death due to any cause (Up to 15.41 months) |
| Phase 1a and 1b: Overall Response Rate (ORR) Based on Modified Response Assessment in Neuro-Oncology (RANO) Criteria in Arm C, D and E | ORR was defined as percentage of participants who achieve a CR or PR per modified RANO criteria. CR defined as that meet all following: 1) Disappearance of all enhancing measurable and non-measurable disease sustained for at least 4 weeks. 2) No new lesions. 3) Participants must be off corticosteroids (or on physiologic replacement doses only). 4) Stable or improved clinical assessments (i.e., neurological examinations). PR defined as that meet all following: 1) >=50% decrease in sum of products of perpendicular diameters or >=65% decrease in total volume of all measurable enhancing lesions compared with baseline, sustained for at least 4 weeks. 2) No new lesion. 3. Steroid dose should be the same or lower compared with baseline scan. 4) Stable or improved clinical assessments. | From first dose of study treatment until death due to any cause (Up to 15.41 months) |
| Phase 1a and 1b: Disease Control Rate (DCR) Based on Modified Response Assessment in Neuro-Oncology (RANO) Criteria in Arm C, D and E | DCR: percentage of participants who achieve CR, PR, or stable disease (SD) per modified RANO criteria. CR: 1) Disappearance of all enhancing measurable and non-measurable disease sustained for at least 4 weeks. 2) No new lesions. 3) Participants must be off corticosteroids. 4) Stable or improved clinical assessments. PR: 1) >=50% decrease in sum of products of perpendicular diameters or >=65% decrease in total volume of all measurable enhancing lesions compared with baseline, sustained for at least 4 weeks. 2) No new lesion. 3) Steroid dose should be same or lower compared with baseline scan. 4) Stable or improved clinical assessments. SD: 1) Does not qualify for CR, PR, or PD. 2) In event that corticosteroid dose was increased without confirmation of PD on neuroimaging, and subsequent follow-up imaging shows steroid increase was required because of PD, last scan considered to show SD was scan obtained when corticosteroid dose was equivalent to baseline dose. | From first dose of study treatment until death due to any cause (Up to 15.41 months) |
| Phase 1a and 1b: Duration of Response (DOR) in Arm C, D and E | DOR was defined as the time from the date of first evidence of objective response (CR or PR) until PD. CR defined as that meet all following: 1) Disappearance of all enhancing measurable and non-measurable disease sustained for at least 4 weeks. 2) No new lesions. 3) Participants must be off corticosteroids (or on physiologic replacement doses only). 4) Stable or improved clinical assessments (i.e., neurological examinations). PR defined as that meet all following: 1) >=50% decrease in sum of products of perpendicular diameters or >=65% decrease in total volume of all measurable enhancing lesions compared with baseline, sustained for at least 4 weeks. 2) No new lesion. 3. Steroid dose should be the same or lower compared with baseline scan. 4) Stable or improved clinical assessments. DOR was analyzed by Kaplan-Meier for participants who have achieved overall response (CR or PR). | From the date of first evidence of objective response until progression (Up to 15.41 months) |
| Phase 1a and 1b: Maximum Plasma Concentration (Cmax) of Selinexor | Cmax of Selinexor was reported. | Cycle 1 Day 1: 2, 4, and 6 hours post-dose (Cycle 1 length = up to 42 days) |
| Los Angeles |
| California |
| 90033 |
| United States |
| University of California | San Francisco | California | 94122 | United States |
| Baptist Hospital of Miami Cancer Institute, 8900 North Kendall Drive | Miami | Florida | 33176 | United States |
| Piedmont Healthcare | Atlanta | Georgia | 30309 | United States |
| Northwestern University Feinberg School of Medicine | Chicago | Illinois | 60611 | United States |
| Massachusetts General Hospital | Boston | Massachusetts | 02114 | United States |
| Dana Farber Cancer Institute | Boston | Massachusetts | 02215 | United States |
| Hackensack Meridian Health, 92 Second Street | Hackensack | New Jersey | 07601 | United States |
| Atlantic Health Systems Hospital Corp. | Morristown | New Jersey | 07960 | United States |
| Northwell Health | Lake Success | New York | 11042 | United States |
| Columbia University Irving Medical Center | New York | New York | 10032 | United States |
| Lenox Hill Hospital-Northwell Health | New York | New York | 10075 | United States |
| Cleveland Clinic | Cleveland | Ohio | 44195 | United States |
| MD Anderson Cancer Center | Houston | Texas | 77030 | United States |
| University of Utah - Huntsman Cancer Institute | Salt Lake City | Utah | 84112 | United States |
| University of Washington - Alvord Brain Tumor Center | Seattle | Washington | 98109 | United States |
| Princess Margaret Hospital (PMH) | Toronto | Ontario | M5G 2MG | Canada |
| FG001 | Arm B: Selinexor + Temozolomide + Radiation Therapy | Participants with nGBM methylated O6-methylguanine-DNA-methyltransferase (mMGMT) received 40 to 80 mg of selinexor oral tablet, QW and 75 milligrams per sqaure meter (mg/m^2) of temozolomide oral capsule, once daily (QD) in combination with 2 Gy RT daily for 5 days per week in a 42-day cycle during Cycle 1 radiation period followed by 60 mg or 80 mg of selinexor oral tablet on Day 1 and 15 in a 28-day Cycle 2, followed by 150 mg/m^2 of temozolomide oral capsule and increase to 200 mg/m^2, daily for 5 days in a 28-day cycle during Cycle 3 to 8 during adjuvant therapy period. Participants continued selinexor weekly until PD. |
| FG002 | Arm C: Selinexor + Lomustine/Carmustine | Participants with recurrent glioblastoma (rGBM) uMGMT or mMGMT received 40 to 80 mg of selinexor oral tablet, QW and 90 to 110 mg/m^2 of lomustine or 150 to 200 mg/m^2 of carmustine (substituted if lomustine is not available) capsule on Day 1 of each 42-days cycle for up to 6 cycles. Participants continued selinexor weekly until PD. |
| FG003 | Arm D: Selinexor + Bevacizumab | Participants with rGBM received 60 to 80 mg of selinexor oral tablet, QW and 10 mg/kg of Bevacizumab intravenous (IV), infusion every 2 weeks (Q2W) in each 28-day cycle until PD, unacceptable adverse events (AEs) or failure to tolerate the study treatment, treatment delay of more than 28 days (except in specific cases with documented approval from the Sponsor), any medically appropriate reason or significant protocol violation (in the opinion of the Investigator), or participant decided to discontinue study treatment, withdraws consent, or became pregnant. |
| FG004 | Arm E: Selinexor + Tumor Treating Fields | Participants with rGBM received 60 to 80 mg of selinexor oral tablet, QW and received scalp application of 200 kilohertz (kHz) of transducer array greater than or equal to (>=) 18 hours per day daily for each 28-day cycle until PD, unacceptable AEs or failure to tolerate the study treatment, treatment delay of more than 28 days (except in specific cases with documented approval from the Sponsor), any medically appropriate reason or significant protocol violation (in the opinion of the Investigator), or participant decided to discontinue study treatment, withdraws consent, or became pregnant. |
| COMPLETED |
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| NOT COMPLETED |
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The safety population consisted of participants who have been assigned to study intervention and who have received >=1 dose of study drug. Due to the early study termination and pre-specified analysis, data was collected/reported according to disease characteristics and combined dose range (60 to 80 mg or 40 to 80 mg) participants received regardless of study phase. The 'per arm' or 'per dose level' data was not collected.
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| ID | Title | Description |
|---|---|---|
| BG000 | Arm A: Selinexor + Radiation Therapy | Participants with nGBM uMGMT received 60 to 80 mg of selinexor oral tablet, once QW in combination with 2 Gy RT daily for 5 days per week in a 42-day cycle during Cycle 1 radiation period followed by 80 mg of selinexor oral tablet on Day 1 and 15 in a 28-day Cycle 2 and subsequently continued at 80 mg of selinexor, QW until PD during adjuvant therapy period. |
| BG001 | Arm B: Selinexor + Temozolomide + Radiation Therapy | Participants with nGBM mMGMT received 40 to 80 mg of selinexor oral tablet, QW and 75 mg/m^2 of temozolomide oral capsule, QD in combination with 2 Gy RT daily for 5 days per week in a 42-day cycle during Cycle 1 radiation period followed by 60 mg or 80 mg of selinexor oral tablet on Day 1 and 15 in a 28-day Cycle 2, followed by 150 mg/m^2 of temozolomide oral capsule and increase to 200 mg/m^2, daily for 5 days in a 28-day cycle during Cycle 3 to 8 during adjuvant therapy period. Participants continued selinexor weekly until PD. |
| BG002 | Arm C: Selinexor + Lomustine/Carmustine | Participants with rGBM uMGMT or mMGMT received 40 to 80 mg of selinexor oral tablet, QW and 90 to 110 mg/m^2 of lomustine or 150 to 200 mg/m^2 of carmustine (substituted if lomustine is not available) capsule on Day 1 of each 42-days cycle for up to 6 cycles. Participants continued selinexor weekly until PD. |
| BG003 | Arm D: Selinexor + Bevacizumab | Participants with rGBM received 60 to 80 mg of selinexor oral tablet, QW and 10 mg/kg of Bevacizumab IV, infusion Q2W in each 28-day cycle until PD, unacceptable AEs or failure to tolerate the study treatment, treatment delay of more than 28 days (except in specific cases with documented approval from the Sponsor), any medically appropriate reason or significant protocol violation (in the opinion of the Investigator), or participant decided to discontinue study treatment, withdraws consent, or became pregnant. |
| BG004 | Arm E: Selinexor + Tumor Treating Fields | Participants with rGBM received 60 to 80 mg of selinexor oral tablet, QW and received scalp application of 200 kHz of transducer array >=18 hours per day daily for each 28-day cycle until PD, unacceptable AEs or failure to tolerate the study treatment, treatment delay of more than 28 days (except in specific cases with documented approval from the Sponsor), any medically appropriate reason or significant protocol violation (in the opinion of the Investigator), or participant decided to discontinue study treatment, withdraws consent, or became pregnant. |
| BG005 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| 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 | ||||||||||||||||||||
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| Primary | Phase 1a and 1b: Maximum Tolerated Dose of Selinexor | MTD was defined as highest dose of selinexor in at which no more than one of six participants experienced a dose-limiting toxicity (DLT). DLT was based on Common Terminology Criteria for Adverse Events (CTCAE) v5.0. | The dose escalation population consisted of all participants in the Dose Escalation Phase who have either had a DLT prior to completion of 1 cycle of therapy, or who had completed a cycle of therapy. Due to the early study termination and pre-specified analysis, data was collected/reported according to disease characteristics and combined dose range (60 to 80 mg or 40 to 80 mg) participants received regardless of study phase. The 'per arm' or 'per dose level' data was not collected. | Posted | Number | milligrams per week | At Cycle 1 (up to 42 days) |
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| Primary | Phase 1a and 1b: Recommended Phase 2 Dose (RP2D) of Selinexor | The RP2D was determined by SRC, based on the MTD and the totality of efficacy and safety data of Phase 1a dose escalation study. RP2D was determined based on the totality of the available safety, efficacy, pharmacokinetic/pharmacodynamic (PK/PD). | The dose escalation population consisted of all participants in the Dose Escalation Phase who have either had a DLT prior to completion of 1 cycle of therapy, or who had completed a cycle of therapy. Due to the early study termination and pre-specified analysis, data was collected/reported according to disease characteristics and combined dose range (60 to 80 mg or 40 to 80 mg) participants received regardless of study phase. The 'per arm' or 'per dose level' data was not collected. | Posted | Number | milligrams per week | From Cycle 1 Day 1 up to 14 days after last dose (up to 15.41 months) (Each Cycle length = up to 42 days) |
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| Primary | Phase 1a and 1b: Number of Participants With Treatment-emergent Adverse Events (TEAEs) With Grade Greater Than or Equal to (>=) 3, Serious TEAEs and Who Discontinued Treatment Due to TEAEs | TEAE: any event that was not present prior to initiation of study treatment or any event already present that worsened in either intensity or frequency following exposure to study treatment. Serious adverse event (SAE): any untoward medical occurrence that, at any dose, resulted in death; was life threatening (i.e., an event in which participant was at risk of death at the time of the event; it did not refer to an event that hypothetically might have caused death if it were more severe); required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; or was a congenital anomaly/birth defect. Important medical events that might not result in death, was life-threatening, or require hospitalization might be considered serious when, based upon appropriate medical judgment, they might jeopardize participant and might require medical or surgical intervention to prevent one of the outcomes listed above. | The safety population consisted of participants in Phase 1a and Phase 1b who have been assigned to study intervention and who have received >=1 dose of study drug. Due to the early study termination and pre-specified analysis, data was collected/reported according to disease characteristics and combined dose range (60 to 80 mg or 40 to 80 mg) participants received regardless of study phase. The 'per arm' or 'per dose level' data was not collected. | Posted | Count of Participants | Participants | From first dose of study treatment up to 30 days post last dose (Up to 16.41 months) |
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| Primary | Phase 1a and 1b: Percentage of Participants With Progression Free Survival at 3 Months | Progression defined as first occurrence of disease progression (PD) per modified Response Assessment in Neuro-Oncology (RANO) including both radiological PD and clinical deterioration. PD per RANO response criteria:1) At least two sequential scans separated by at >=4 weeks both exhibiting >=25 percent (%) increase in sum of products of perpendicular diameters or >=40% increase in total volume of enhancing lesions. 2) In case where baseline or best response demonstrates no measurable enhancing disease, then any new measurable (>10mm*10mm) enhancing lesions considered PD after confirmed by a subsequent scan >=4 weeks exhibiting >=25% increase in sum of products of perpendicular diameters or >=40% increase in total volume of enhancing lesions relative to scan first illustrating new measurable disease. 3) Clear clinical deterioration not attributable to other causes apart from tumor or attributable to changes in steroid dose. 4) Failure to return for evaluation as a result of death. | The modified Intent-to-Treat (mITT) population consisted of participants in Phase 1a and Phase 1b who have been assigned to study intervention and who have received >=1 dose of study drug. Due to the early study termination and pre-specified analysis, data was collected/reported according to disease characteristics and combined dose range (60 to 80 mg or 40 to 80 mg) participants received regardless of study phase. The 'per arm' or 'per dose level' data was not collected. | Posted | Number | percentage of participants | At 3 Months |
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| Primary | Phase 1a and 1b: Overall Survival (OS) | OS was defined as the time from the date of randomization until death due to any cause or until lost to follow-up for all participants. | The mITT population consisted of participants in Phase 1a and Phase 1b who have been assigned to study intervention and who have received >=1 dose of study drug. Due to the early study termination and pre-specified analysis, data was collected/reported according to disease characteristics and combined dose range (60 to 80 mg or 40 to 80 mg) participants received regardless of study phase. The 'per arm' or 'per dose level' data was not collected. | Posted | Median | 95% Confidence Interval | months | From date of randomization to the date of death due to any cause or until lost to follow-up (up to 20 months) |
| |||||||||||||||||||||||||||
| Secondary | Phase 1a and 1b: Time to Progression (TTP) | TTP was defined for participants as the duration from start of treatment to the date of PD, or death due to PD, whichever occurs first. PD per RANO response criteria: 1) At least two sequential scans separated by at >=4 weeks both exhibiting >=25 percent (%) increase in sum of products of perpendicular diameters or >=40% increase in total volume of enhancing lesions. 2) In case where baseline or best response demonstrates no measurable enhancing disease, then any new measurable (>10mm*10mm) enhancing lesions considered PD after confirmed by a subsequent scan >=4 weeks exhibiting >=25% increase in sum of products of perpendicular diameters or >=40% increase in total volume of enhancing lesions relative to scan first illustrating new measurable disease. 3) Clear clinical deterioration not attributable to other causes apart from tumor or attributable to changes in steroid dose. 4) Failure to return for evaluation as a result of death or deteriorating condition. | The mITT population consisted of participants in Phase 1a and Phase 1b who have been assigned to study intervention and who have received >=1 dose of study drug. Due to the early study termination and pre-specified analysis, data was collected/reported according to disease characteristics and combined dose range (60 to 80 mg or 40 to 80 mg) participants received regardless of study phase. The 'per arm' or 'per dose level' data was not collected. | Posted | Median | 95% Confidence Interval | months | From first dose study treatment until progression or death due to progression (Up to 15.41 months) |
| |||||||||||||||||||||||||||
| Secondary | Phase 1a and 1b: Progressive Free Survival (PFS) | Progression defined as first occurrence of PD per modified RANO including both radiological PD and clinical deterioration. PD per RANO response criteria: 1) At least two sequential scans separated by at >=4 weeks both exhibiting >=25 percent (%) increase in sum of products of perpendicular diameters or >=40% increase in total volume of enhancing lesions. 2) In case where baseline or best response demonstrates no measurable enhancing disease, then any new measurable (>10mm*10mm) enhancing lesions considered PD after confirmed by a subsequent scan >=4 weeks exhibiting >=25% increase in sum of products of perpendicular diameters or >=40% increase in total volume of enhancing lesions relative to scan first illustrating new measurable disease. 3) Clear clinical deterioration not attributable to other causes apart from tumor or attributable to changes in steroid dose. 4) Failure to return for evaluation as a result of death or deteriorating condition. | The mITT population consisted of participants in Phase 1a and Phase 1b who have been assigned to study intervention and who have received >=1 dose of study drug. Due to the early study termination and pre-specified analysis, data was collected/reported according to disease characteristics and combined dose range (60 to 80 mg or 40 to 80 mg) participants received regardless of study phase. The 'per arm' or 'per dose level' data was not collected. | Posted | Median | 95% Confidence Interval | months | From first dose of study treatment until progression or death due to any cause (Up to 15.41 months) |
| |||||||||||||||||||||||||||
| Secondary | Phase 1a and 1b: Overall Response Rate (ORR) Based on Modified Response Assessment in Neuro-Oncology (RANO) Criteria in Arm C, D and E | ORR was defined as percentage of participants who achieve a CR or PR per modified RANO criteria. CR defined as that meet all following: 1) Disappearance of all enhancing measurable and non-measurable disease sustained for at least 4 weeks. 2) No new lesions. 3) Participants must be off corticosteroids (or on physiologic replacement doses only). 4) Stable or improved clinical assessments (i.e., neurological examinations). PR defined as that meet all following: 1) >=50% decrease in sum of products of perpendicular diameters or >=65% decrease in total volume of all measurable enhancing lesions compared with baseline, sustained for at least 4 weeks. 2) No new lesion. 3. Steroid dose should be the same or lower compared with baseline scan. 4) Stable or improved clinical assessments. | The mITT population consisted of participants in Phase 1a and Phase 1b who have been assigned to study intervention and who have received >=1 dose of study drug. Due to the early study termination and pre-specified analysis, data was collected/reported according to disease characteristics and combined dose range (60 to 80 mg or 40 to 80 mg) participants received regardless of study phase. The 'per arm' or 'per dose level' data was not collected. | Posted | Number | 95% Confidence Interval | percentage of participants | From first dose of study treatment until death due to any cause (Up to 15.41 months) |
| |||||||||||||||||||||||||||
| Secondary | Phase 1a and 1b: Disease Control Rate (DCR) Based on Modified Response Assessment in Neuro-Oncology (RANO) Criteria in Arm C, D and E | DCR: percentage of participants who achieve CR, PR, or stable disease (SD) per modified RANO criteria. CR: 1) Disappearance of all enhancing measurable and non-measurable disease sustained for at least 4 weeks. 2) No new lesions. 3) Participants must be off corticosteroids. 4) Stable or improved clinical assessments. PR: 1) >=50% decrease in sum of products of perpendicular diameters or >=65% decrease in total volume of all measurable enhancing lesions compared with baseline, sustained for at least 4 weeks. 2) No new lesion. 3) Steroid dose should be same or lower compared with baseline scan. 4) Stable or improved clinical assessments. SD: 1) Does not qualify for CR, PR, or PD. 2) In event that corticosteroid dose was increased without confirmation of PD on neuroimaging, and subsequent follow-up imaging shows steroid increase was required because of PD, last scan considered to show SD was scan obtained when corticosteroid dose was equivalent to baseline dose. | The mITT population consisted of participants in Phase 1a and Phase 1b who have been assigned to study intervention and who have received >=1 dose of study drug. Due to the early study termination and pre-specified analysis, data was collected/reported according to disease characteristics and combined dose range (60 to 80 mg or 40 to 80 mg) participants received regardless of study phase. The 'per arm' or 'per dose level' data was not collected. | Posted | Number | 95% Confidence Interval | percentage of participants | From first dose of study treatment until death due to any cause (Up to 15.41 months) |
| |||||||||||||||||||||||||||
| Secondary | Phase 1a and 1b: Duration of Response (DOR) in Arm C, D and E | DOR was defined as the time from the date of first evidence of objective response (CR or PR) until PD. CR defined as that meet all following: 1) Disappearance of all enhancing measurable and non-measurable disease sustained for at least 4 weeks. 2) No new lesions. 3) Participants must be off corticosteroids (or on physiologic replacement doses only). 4) Stable or improved clinical assessments (i.e., neurological examinations). PR defined as that meet all following: 1) >=50% decrease in sum of products of perpendicular diameters or >=65% decrease in total volume of all measurable enhancing lesions compared with baseline, sustained for at least 4 weeks. 2) No new lesion. 3. Steroid dose should be the same or lower compared with baseline scan. 4) Stable or improved clinical assessments. DOR was analyzed by Kaplan-Meier for participants who have achieved overall response (CR or PR). | The mITT population. Here, "overall number of participants analyzed" signifies those participants who had CR or PR. Due to the early study termination and pre-specified analysis, data was collected/reported according to disease characteristics and combined dose range (60 to 80 mg or 40 to 80 mg) participants received regardless of study phase. The 'per arm' or 'per dose level' data was not collected. | Posted | Median | 95% Confidence Interval | months | From the date of first evidence of objective response until progression (Up to 15.41 months) |
| |||||||||||||||||||||||||||
| Secondary | Phase 1a and 1b: Maximum Plasma Concentration (Cmax) of Selinexor | Cmax of Selinexor was reported. | PK analysis set. Here, "overall number of participants analyzed" signifies those participants who are evaluable for this outcome. Due to the early study termination and pre-specified analysis, data was collected/reported for Cmax was calculated across treatment for each patient per dose level (40 mg, 60 mg and 80 mg) considering no accumulation of selinexor. | Posted | Geometric Mean | Geometric Coefficient of Variation | nanograms per milliliter (ng/mL) | Cycle 1 Day 1: 2, 4, and 6 hours post-dose (Cycle 1 length = up to 42 days) |
|
|
From first dose of study treatment up to 30 days post last dose (Up to 20 months)
The safety population consisted of participants who have been assigned to study intervention and who have received >=1 dose of study drug. Due to the early study termination and pre-specified analysis, data was collected/reported according to disease characteristics and combined dose range (60 to 80 mg or 40 to 80 mg) participants received regardless of study phase. The 'per arm' or 'per dose level' data was not collected.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Arm A: Selinexor + Radiation Therapy | Participants with nGBM uMGMT received 60 to 80 mg of selinexor oral tablet, once QW in combination with 2 Gy RT daily for 5 days per week in a 42-day cycle during Cycle 1 radiation period followed by 80 mg of selinexor oral tablet on Day 1 and 15 in a 28-day Cycle 2 and subsequently continued at 80 mg of selinexor, QW until PD during adjuvant therapy period. | 15 | 23 | 6 | 23 | 23 | 23 |
| EG001 | Arm B: Selinexor + Temozolomide + Radiation Therapy | Participants with nGBM mMGMT received 40 to 80 mg of selinexor oral tablet, QW and 75 mg/m^2 of temozolomide oral capsule, QD in combination with 2 Gy RT daily for 5 days per week in a 42-day cycle during Cycle 1 radiation period followed by 60 mg or 80 mg of selinexor oral tablet on Day 1 and 15 in a 28-day Cycle 2, followed by 150 mg/m^2 of temozolomide oral capsule and increase to 200 mg/m^2, daily for 5 days in a 28-day cycle during Cycle 3 to 8 during adjuvant therapy period. Participants continued selinexor weekly until PD. | 7 | 15 | 5 | 15 | 15 | 15 |
| EG002 | Arm C: Selinexor + Lomustine/Carmustine | Participants with rGBM uMGMT or mMGMT received 40 to 80 mg of selinexor oral tablet, QW and 90 to 110 mg/m^2 of lomustine or 150 to 200 mg/m^2 of carmustine (substituted if lomustine is not available) capsule on Day 1 of each 42-days cycle for up to 6 cycles. Participants continued selinexor weekly until PD. | 15 | 19 | 6 | 19 | 19 | 19 |
| EG003 | Arm D: Selinexor + Bevacizumab | Participants with rGBM received 60 to 80 mg of selinexor oral tablet, QW and 10 mg/kg of Bevacizumab IV, infusion Q2W in each 28-day cycle until PD, unacceptable AEs or failure to tolerate the study treatment, treatment delay of more than 28 days (except in specific cases with documented approval from the Sponsor), any medically appropriate reason or significant protocol violation (in the opinion of the Investigator), or participant decided to discontinue study treatment, withdraws consent, or became pregnant. | 11 | 14 | 3 | 14 | 14 | 14 |
| EG004 | Arm E: Selinexor + Tumor Treating Fields | Participants with rGBM received 60 to 80 mg of selinexor oral tablet, QW and received scalp application of 200 kHz of transducer array >=18 hours per day daily for each 28-day cycle until PD, unacceptable AEs or failure to tolerate the study treatment, treatment delay of more than 28 days (except in specific cases with documented approval from the Sponsor), any medically appropriate reason or significant protocol violation (in the opinion of the Investigator), or participant decided to discontinue study treatment, withdraws consent, or became pregnant. | 3 | 3 | 1 | 3 | 3 | 3 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Cerebrovascular accident | Nervous system disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Febrile neutropenia | Blood and lymphatic system disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Hemiparesis | Nervous system disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Seizure | Nervous system disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Agitation | Metabolism and nutrition disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Cellulitis | Infections and infestations | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Deep vein thrombosis | Vascular disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Dehydration | Metabolism and nutrition disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Escherichia urinary tract infection | Infections and infestations | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Fall | Injury, poisoning and procedural complications | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Hydrocephalus | Nervous system disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Non-cardiac chest pain | General disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Overdose | Injury, poisoning and procedural complications | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Respiratory alkalosis | Respiratory, thoracic and mediastinal disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Sinus bradycardia | Cardiac disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Sinusitis | Infections and infestations | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Urosepsis | Infections and infestations | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| COVID-19 | Infections and infestations | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Postoperative wound infection | Infections and infestations | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Traumatic intracranial haemorrhage | Injury, poisoning and procedural complications | MedDRA version 24.0 | Non-systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Neutropenia | Blood and lymphatic system disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Lymphopenia | Blood and lymphatic system disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Leukopenia | Blood and lymphatic system disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Anaemia | Blood and lymphatic system disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Sinus bradycardia | Cardiac disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Sinus tachycardia | Cardiac disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Vision blurred | Eye disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Fatigue | General disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Gait disturbance | General disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Oedema peripheral | General disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| COVID-19 | Infections and infestations | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Skin infection | Infections and infestations | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Fall | Injury, poisoning and procedural complications | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Contusion | Injury, poisoning and procedural complications | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Radiation skin injury | Injury, poisoning and procedural complications | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Weight decreased | Investigations | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Alanine aminotransferase increased | Investigations | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Aspartate aminotransferase increased | Investigations | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Blood creatinine increased | Investigations | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Weight increased | Investigations | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Decreased appetite | Metabolism and nutrition disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Hyponatraemia | Metabolism and nutrition disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Dehydration | Metabolism and nutrition disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Muscular weakness | Musculoskeletal and connective tissue disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Seizure | Nervous system disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Hemiparesis | Nervous system disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Dysgeusia | Nervous system disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Facial paresis | Nervous system disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Aphasia | Nervous system disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Cognitive disorder | Nervous system disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Memory impairment | Nervous system disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Dysarthria | Nervous system disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Somnolence | Nervous system disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Depression | Psychiatric disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Confusional state | Psychiatric disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Agitation | Psychiatric disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Anxiety | Psychiatric disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Urinary retention | Renal and urinary disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Nasal congestion | Respiratory, thoracic and mediastinal disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Rhinitis allergic | Respiratory, thoracic and mediastinal disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Alopecia | Skin and subcutaneous tissue disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Rash maculo-papular | Skin and subcutaneous tissue disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Hypertension | Vascular disorders | MedDRA version 24.0 | Non-systematic Assessment |
| |
| Hypotension | Vascular disorders | MedDRA version 24.0 | Non-systematic Assessment |
|
The trial was terminated during the Phase 1b portion of the trial as the initial responses to selinexor treatment were not supportive of continued investigation in glioblastoma, therefore there was no reporting of the Phase 2 outcomes.
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Karyopharm Medical Information | Karyopharm Therapeutics Inc | (888) 209-9326 | clinicaltrials@karyopharm.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Nov 19, 2021 | Jul 25, 2024 | SAP_001.pdf |
Not provided
| ID | Term |
|---|---|
| D005909 | Glioblastoma |
| ID | Term |
|---|---|
| D001254 | Astrocytoma |
| D005910 | Glioma |
| D018302 | Neoplasms, Neuroepithelial |
| D017599 | Neuroectodermal Tumors |
| D009373 | Neoplasms, Germ Cell and Embryonal |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009380 | Neoplasms, Nerve Tissue |
Not provided
Not provided
| ID | Term |
|---|---|
| C585161 | selinexor |
| D000077204 | Temozolomide |
| D008130 | Lomustine |
| D000068258 | Bevacizumab |
| D002330 | Carmustine |
| ID | Term |
|---|---|
| D003606 | Dacarbazine |
| D014226 | Triazenes |
| D009930 | Organic Chemicals |
| D007093 | Imidazoles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D009607 | Nitrosourea Compounds |
| D014508 | Urea |
| D000577 | Amides |
| D009603 | Nitroso Compounds |
| D061067 | Antibodies, Monoclonal, Humanized |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
Not provided
Not provided
| Male |
|
| Not Hispanic or Latino |
|
| Unknown or Not Reported |
|
| Asian |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
| OG002 | Arm C: Selinexor + Lomustine/Carmustine | Participants with rGBM uMGMT or mMGMT received 40 to 80 mg of selinexor oral tablet, QW and 90 to 110 mg/m^2 of lomustine or 150 to 200 mg/m^2 of carmustine (substituted if lomustine is not available) capsule on Day 1 of each 42-days cycle for up to 6 cycles. Participants continued selinexor weekly until PD. |
| OG003 | Arm D: Selinexor + Bevacizumab | Participants with rGBM received 60 to 80 mg of selinexor oral tablet, QW and 10 mg/kg of Bevacizumab IV, infusion Q2W in each 28-day cycle until PD, unacceptable AEs or failure to tolerate the study treatment, treatment delay of more than 28 days (except in specific cases with documented approval from the Sponsor), any medically appropriate reason or significant protocol violation (in the opinion of the Investigator), or participant decided to discontinue study treatment, withdraws consent, or became pregnant. |
| OG004 | Arm E: Selinexor + Tumor Treating Fields | Participants with rGBM received 60 to 80 mg of selinexor oral tablet, QW and received scalp application of 200 kHz of transducer array >=18 hours per day daily for each 28-day cycle until PD, unacceptable AEs or failure to tolerate the study treatment, treatment delay of more than 28 days (except in specific cases with documented approval from the Sponsor), any medically appropriate reason or significant protocol violation (in the opinion of the Investigator), or participant decided to discontinue study treatment, withdraws consent, or became pregnant. |
|
|
Participants with nGBM uMGMT received 60 to 80 mg of selinexor oral tablet, once QW in combination with 2 Gy RT daily for 5 days per week in a 42-day cycle during Cycle 1 radiation period followed by 80 mg of selinexor oral tablet on Day 1 and 15 in a 28-day Cycle 2 and subsequently continued at 80 mg of selinexor, QW until PD during adjuvant therapy period. |
| OG001 | Arm B: Selinexor + Temozolomide + Radiation Therapy | Participants with nGBM mMGMT received 40 to 80 mg of selinexor oral tablet, QW and 75 mg/m^2 of temozolomide oral capsule, QD in combination with 2 Gy RT daily for 5 days per week in a 42-day cycle during Cycle 1 radiation period followed by 60 mg or 80 mg of selinexor oral tablet on Day 1 and 15 in a 28-day Cycle 2, followed by 150 mg/m^2 of temozolomide oral capsule and increase to 200 mg/m^2, daily for 5 days in a 28-day cycle during Cycle 3 to 8 during adjuvant therapy period. Participants continued selinexor weekly until PD. |
| OG002 | Arm C: Selinexor + Lomustine/Carmustine | Participants with rGBM uMGMT or mMGMT received 40 to 80 mg of selinexor oral tablet, QW and 90 to 110 mg/m^2 of lomustine or 150 to 200 mg/m^2 of carmustine (substituted if lomustine is not available) capsule on Day 1 of each 42-days cycle for up to 6 cycles. Participants continued selinexor weekly until PD. |
| OG003 | Arm D: Selinexor + Bevacizumab | Participants with rGBM received 60 to 80 mg of selinexor oral tablet, QW and 10 mg/kg of Bevacizumab IV, infusion Q2W in each 28-day cycle until PD, unacceptable AEs or failure to tolerate the study treatment, treatment delay of more than 28 days (except in specific cases with documented approval from the Sponsor), any medically appropriate reason or significant protocol violation (in the opinion of the Investigator), or participant decided to discontinue study treatment, withdraws consent, or became pregnant. |
| OG004 | Arm E: Selinexor + Tumor Treating Fields | Participants with rGBM received 60 to 80 mg of selinexor oral tablet, QW and received scalp application of 200 kHz of transducer array >=18 hours per day daily for each 28-day cycle until PD, unacceptable AEs or failure to tolerate the study treatment, treatment delay of more than 28 days (except in specific cases with documented approval from the Sponsor), any medically appropriate reason or significant protocol violation (in the opinion of the Investigator), or participant decided to discontinue study treatment, withdraws consent, or became pregnant. |
|
|
| OG001 | Arm B: Selinexor + Temozolomide + Radiation Therapy | Participants with nGBM mMGMT received 40 to 80 mg of selinexor oral tablet, QW and 75 mg/m^2 of temozolomide oral capsule, QD in combination with 2 Gy RT daily for 5 days per week in a 42-day cycle during Cycle 1 radiation period followed by 60 mg or 80 mg of selinexor oral tablet on Day 1 and 15 in a 28-day Cycle 2, followed by 150 mg/m^2 of temozolomide oral capsule and increase to 200 mg/m^2, daily for 5 days in a 28-day cycle during Cycle 3 to 8 during adjuvant therapy period. Participants continued selinexor weekly until PD. |
| OG002 | Arm C: Selinexor + Lomustine/Carmustine | Participants with rGBM uMGMT or mMGMT received 40 to 80 mg of selinexor oral tablet, QW and 90 to 110 mg/m^2 of lomustine or 150 to 200 mg/m^2 of carmustine (substituted if lomustine is not available) capsule on Day 1 of each 42-days cycle for up to 6 cycles. Participants continued selinexor weekly until PD. |
| OG003 | Arm D: Selinexor + Bevacizumab | Participants with rGBM received 60 to 80 mg of selinexor oral tablet, QW and 10 mg/kg of Bevacizumab IV, infusion Q2W in each 28-day cycle until PD, unacceptable AEs or failure to tolerate the study treatment, treatment delay of more than 28 days (except in specific cases with documented approval from the Sponsor), any medically appropriate reason or significant protocol violation (in the opinion of the Investigator), or participant decided to discontinue study treatment, withdraws consent, or became pregnant. |
| OG004 | Arm E: Selinexor + Tumor Treating Fields | Participants with rGBM received 60 to 80 mg of selinexor oral tablet, QW and received scalp application of 200 kHz of transducer array >=18 hours per day daily for each 28-day cycle until PD, unacceptable AEs or failure to tolerate the study treatment, treatment delay of more than 28 days (except in specific cases with documented approval from the Sponsor), any medically appropriate reason or significant protocol violation (in the opinion of the Investigator), or participant decided to discontinue study treatment, withdraws consent, or became pregnant. |
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| OG002 | Arm C: Selinexor + Lomustine/Carmustine | Participants with rGBM uMGMT or mMGMT received 40 to 80 mg of selinexor oral tablet, QW and 90 to 110 mg/m^2 of lomustine or 150 to 200 mg/m^2 of carmustine (substituted if lomustine is not available) capsule on Day 1 of each 42-days cycle for up to 6 cycles. Participants continued selinexor weekly until PD. |
| OG003 | Arm D: Selinexor + Bevacizumab | Participants with rGBM received 60 to 80 mg of selinexor oral tablet, QW and 10 mg/kg of Bevacizumab IV, infusion Q2W in each 28-day cycle until PD, unacceptable AEs or failure to tolerate the study treatment, treatment delay of more than 28 days (except in specific cases with documented approval from the Sponsor), any medically appropriate reason or significant protocol violation (in the opinion of the Investigator), or participant decided to discontinue study treatment, withdraws consent, or became pregnant. |
| OG004 | Arm E: Selinexor + Tumor Treating Fields | Participants with rGBM received 60 to 80 mg of selinexor oral tablet, QW and received scalp application of 200 kHz of transducer array >=18 hours per day daily for each 28-day cycle until PD, unacceptable AEs or failure to tolerate the study treatment, treatment delay of more than 28 days (except in specific cases with documented approval from the Sponsor), any medically appropriate reason or significant protocol violation (in the opinion of the Investigator), or participant decided to discontinue study treatment, withdraws consent, or became pregnant. |
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| OG001 | Arm B: Selinexor + Temozolomide + Radiation Therapy | Participants with nGBM mMGMT received 40 to 80 mg of selinexor oral tablet, QW and 75 mg/m^2 of temozolomide oral capsule, QD in combination with 2 Gy RT daily for 5 days per week in a 42-day cycle during Cycle 1 radiation period followed by 60 mg or 80 mg of selinexor oral tablet on Day 1 and 15 in a 28-day Cycle 2, followed by 150 mg/m^2 of temozolomide oral capsule and increase to 200 mg/m^2, daily for 5 days in a 28-day cycle during Cycle 3 to 8 during adjuvant therapy period. Participants continued selinexor weekly until PD. |
| OG002 | Arm C: Selinexor + Lomustine/Carmustine | Participants with rGBM uMGMT or mMGMT received 40 to 80 mg of selinexor oral tablet, QW and 90 to 110 mg/m^2 of lomustine or 150 to 200 mg/m^2 of carmustine (substituted if lomustine is not available) capsule on Day 1 of each 42-days cycle for up to 6 cycles. Participants continued selinexor weekly until PD. |
| OG003 | Arm D: Selinexor + Bevacizumab | Participants with rGBM received 60 to 80 mg of selinexor oral tablet, QW and 10 mg/kg of Bevacizumab IV, infusion Q2W in each 28-day cycle until PD, unacceptable AEs or failure to tolerate the study treatment, treatment delay of more than 28 days (except in specific cases with documented approval from the Sponsor), any medically appropriate reason or significant protocol violation (in the opinion of the Investigator), or participant decided to discontinue study treatment, withdraws consent, or became pregnant. |
| OG004 | Arm E: Selinexor + Tumor Treating Fields | Participants with rGBM received 60 to 80 mg of selinexor oral tablet, QW and received scalp application of 200 kHz of transducer array >=18 hours per day daily for each 28-day cycle until PD, unacceptable AEs or failure to tolerate the study treatment, treatment delay of more than 28 days (except in specific cases with documented approval from the Sponsor), any medically appropriate reason or significant protocol violation (in the opinion of the Investigator), or participant decided to discontinue study treatment, withdraws consent, or became pregnant. |
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| OG001 | Arm B: Selinexor + Temozolomide + Radiation Therapy | Participants with nGBM mMGMT received 40 to 80 mg of selinexor oral tablet, QW and 75 mg/m^2 of temozolomide oral capsule, QD in combination with 2 Gy RT daily for 5 days per week in a 42-day cycle during Cycle 1 radiation period followed by 60 mg or 80 mg of selinexor oral tablet on Day 1 and 15 in a 28-day Cycle 2, followed by 150 mg/m^2 of temozolomide oral capsule and increase to 200 mg/m^2, daily for 5 days in a 28-day cycle during Cycle 3 to 8 during adjuvant therapy period. Participants continued selinexor weekly until PD. |
| OG002 | Arm C: Selinexor + Lomustine/Carmustine | Participants with rGBM uMGMT or mMGMT received 40 to 80 mg of selinexor oral tablet, QW and 90 to 110 mg/m^2 of lomustine or 150 to 200 mg/m^2 of carmustine (substituted if lomustine is not available) capsule on Day 1 of each 42-days cycle for up to 6 cycles. Participants continued selinexor weekly until PD. |
| OG003 | Arm D: Selinexor + Bevacizumab | Participants with rGBM received 60 to 80 mg of selinexor oral tablet, QW and 10 mg/kg of Bevacizumab IV, infusion Q2W in each 28-day cycle until PD, unacceptable AEs or failure to tolerate the study treatment, treatment delay of more than 28 days (except in specific cases with documented approval from the Sponsor), any medically appropriate reason or significant protocol violation (in the opinion of the Investigator), or participant decided to discontinue study treatment, withdraws consent, or became pregnant. |
| OG004 | Arm E: Selinexor + Tumor Treating Fields | Participants with rGBM received 60 to 80 mg of selinexor oral tablet, QW and received scalp application of 200 kHz of transducer array >=18 hours per day daily for each 28-day cycle until PD, unacceptable AEs or failure to tolerate the study treatment, treatment delay of more than 28 days (except in specific cases with documented approval from the Sponsor), any medically appropriate reason or significant protocol violation (in the opinion of the Investigator), or participant decided to discontinue study treatment, withdraws consent, or became pregnant. |
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| OG001 | Arm D: Selinexor + Bevacizumab | Participants with rGBM received 60 to 80 mg of selinexor oral tablet, QW and 10 mg/kg of Bevacizumab IV, infusion Q2W in each 28-day cycle until PD, unacceptable AEs or failure to tolerate the study treatment, treatment delay of more than 28 days (except in specific cases with documented approval from the Sponsor), any medically appropriate reason or significant protocol violation (in the opinion of the Investigator), or participant decided to discontinue study treatment, withdraws consent, or became pregnant. |
| OG002 | Arm E: Selinexor + Tumor Treating Fields | Participants with rGBM received 60 to 80 mg of selinexor oral tablet, QW and received scalp application of 200 kHz of transducer array >=18 hours per day daily for each 28-day cycle until PD, unacceptable AEs or failure to tolerate the study treatment, treatment delay of more than 28 days (except in specific cases with documented approval from the Sponsor), any medically appropriate reason or significant protocol violation (in the opinion of the Investigator), or participant decided to discontinue study treatment, withdraws consent, or became pregnant. |
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Participants with rGBM uMGMT or mMGMT received 40 to 80 mg of selinexor oral tablet, QW and 90 to 110 mg/m^2 of lomustine or 150 to 200 mg/m^2 of carmustine (substituted if lomustine is not available) capsule on Day 1 of each 42-days cycle for up to 6 cycles. Participants continued selinexor weekly until PD. |
| OG001 | Arm D: Selinexor + Bevacizumab | Participants with rGBM received 60 to 80 mg of selinexor oral tablet, QW and 10 mg/kg of Bevacizumab IV, infusion Q2W in each 28-day cycle until PD, unacceptable AEs or failure to tolerate the study treatment, treatment delay of more than 28 days (except in specific cases with documented approval from the Sponsor), any medically appropriate reason or significant protocol violation (in the opinion of the Investigator), or participant decided to discontinue study treatment, withdraws consent, or became pregnant. |
| OG002 | Arm E: Selinexor + Tumor Treating Fields | Participants with rGBM received 60 to 80 mg of selinexor oral tablet, QW and received scalp application of 200 kHz of transducer array >=18 hours per day daily for each 28-day cycle until PD, unacceptable AEs or failure to tolerate the study treatment, treatment delay of more than 28 days (except in specific cases with documented approval from the Sponsor), any medically appropriate reason or significant protocol violation (in the opinion of the Investigator), or participant decided to discontinue study treatment, withdraws consent, or became pregnant. |
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| OG001 | Arm D: Selinexor + Bevacizumab | Participants with rGBM received 60 to 80 mg of selinexor oral tablet, QW and 10 mg/kg of Bevacizumab IV, infusion Q2W in each 28-day cycle until PD, unacceptable AEs or failure to tolerate the study treatment, treatment delay of more than 28 days (except in specific cases with documented approval from the Sponsor), any medically appropriate reason or significant protocol violation (in the opinion of the Investigator), or participant decided to discontinue study treatment, withdraws consent, or became pregnant. |
| OG002 | Arm E: Selinexor + Tumor Treating Fields | Participants with rGBM received 60 to 80 mg of selinexor oral tablet, QW and received scalp application of 200 kHz of transducer array >=18 hours per day daily for each 28-day cycle until PD, unacceptable AEs or failure to tolerate the study treatment, treatment delay of more than 28 days (except in specific cases with documented approval from the Sponsor), any medically appropriate reason or significant protocol violation (in the opinion of the Investigator), or participant decided to discontinue study treatment, withdraws consent, or became pregnant. |
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