74 Participants Needed

A Study of Selinexor in Combination With Standard of Care Therapy for Newly Diagnosed or Recurrent Glioblastoma

Recruiting at 17 trial locations
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Overseen ByEric Sbar VP of Clinical Development, DO
Age: 18+
Sex: Any
Trial Phase: Phase 1 & 2
Sponsor: Karyopharm Therapeutics Inc
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)

Trial Summary

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, there are restrictions on certain prior treatments, such as chemotherapy and investigational agents, which must be stopped at least 4 weeks before starting the study treatment.

What data supports the effectiveness of the drug combination including Bevacizumab, Carmustine, Lomustine, Selinexor, and Temozolomide for treating brain tumors?

Research shows that Temozolomide (TMZ) is effective in treating malignant brain gliomas, and when combined with other drugs like Carmustine (BCNU) and Lomustine (CCNU), it can be part of a successful treatment plan for brain tumors. Additionally, studies indicate that combining TMZ with radiotherapy can be safe and effective for treating anaplastic astrocytoma, a type of brain tumor.12345

Is the treatment generally safe for humans?

Research shows that temozolomide (TMZ) and carmustine (BCNU) have been studied for safety in treating brain tumors. Some patients experienced myelosuppression (a decrease in bone marrow activity leading to fewer blood cells) as a side effect, indicating that while the treatment is feasible, it may have significant side effects.12467

What makes the drug combination of Carmustine, Lomustine, Selinexor, Radiation therapy, and Temozolomide unique?

This drug combination is unique because it includes Selinexor, a novel agent that inhibits nuclear export, potentially enhancing the effectiveness of chemotherapy and radiation therapy by keeping tumor-suppressing proteins inside the cell nucleus where they can work. This approach may offer a new mechanism of action compared to traditional treatments.89101112

What is the purpose of this trial?

This trial tests selinexor combined with standard treatments for patients with new or recurring brain cancer. Selinexor aims to stop cancer cells from growing and make them more susceptible to other therapies. Selinexor has shown positive responses and manageable side effects in patients with recurrent glioblastoma.

Research Team

AB

Andrew B Lassman, MD

Principal Investigator

Columbia University

Eligibility Criteria

Inclusion Criteria

Glioblastoma that is newly diagnosed or relapsed after 1 to 2 line of systemic therapy is eligible for this study
Renal function: calculated (Cockcroft-Gault) or measured creatinine clearance ≥30 milliliter per minute (mL/min)
Limited to supratentorial disease for Arm E only.
See 13 more

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
See 12 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase 1a Dose Finding

Participants receive selinexor in combination with standard of care to determine the maximum tolerated dose

Up to 42 days
Weekly visits for dose escalation

Phase 1b Dose Expansion

Participants continue to receive selinexor at the recommended phase 2 dose to further evaluate safety and efficacy

Up to 15.41 months
Bi-weekly visits for monitoring

Phase 2 Randomized Efficacy Exploration

Participants are randomized to different treatment arms to evaluate the efficacy of selinexor in combination with various therapies

Up to 20 months
Monthly visits for efficacy assessment

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks
2 visits (in-person)

Treatment Details

Interventions

  • Bevacizumab
  • Carmustine
  • Lomustine (CCNU)
  • Selinexor
  • Standard Fractionated Radiation therapy (RT)
  • Temozolomide (TMZ)
  • TTField
Participant Groups
8Treatment groups
Experimental Treatment
Active Control
Group I: Phase 1: Arm B: Selinexor+Temozolomide+Radiation TherapyExperimental Treatment3 Interventions
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.
Group II: Phase 1: Arm A: Selinexor+Radiation TherapyExperimental Treatment2 Interventions
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.
Group III: Arm E: Selinexor+TTFieldExperimental Treatment2 Interventions
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.
Group IV: Arm D: Selinexor+BevacizumabExperimental Treatment2 Interventions
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.
Group V: Arm C: Selinexor+Lomustine/CarmustineExperimental Treatment3 Interventions
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.
Group VI: Arm B Control: Temozolomide+Radiation TherapyActive Control2 Interventions
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.
Group VII: Arm A Control: Temozolomide+Radiation TherapyActive Control2 Interventions
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.
Group VIII: Arm C Control: Lomustine/CarmustineActive Control2 Interventions
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.

Carmustine is already approved in United States, European Union, Canada for the following indications:

🇺🇸
Approved in United States as BiCNU for:
  • Brain tumors
  • Multiple myeloma
  • Hodgkin's disease
  • Non-Hodgkin's lymphoma
🇪🇺
Approved in European Union as Carmubris for:
  • Brain tumors
  • Multiple myeloma
  • Hodgkin's disease
  • Non-Hodgkin's lymphoma
🇨🇦
Approved in Canada as BCNU for:
  • Brain tumors
  • Multiple myeloma
  • Hodgkin's disease
  • Non-Hodgkin's lymphoma

Find a Clinic Near You

Who Is Running the Clinical Trial?

Karyopharm Therapeutics Inc

Lead Sponsor

Trials
89
Recruited
7,200+

Richard Paulson

Karyopharm Therapeutics Inc

Chief Executive Officer since 2021

MBA from the University of Toronto's Rotman School of Management

Reshma Rangwala

Karyopharm Therapeutics Inc

Chief Medical Officer since 2023

MD, PhD

Findings from Research

In a study of 151 patients with recurrent glioblastoma multiforme or anaplastic astrocytoma, temozolomide (TMZ) demonstrated significantly better progression-free survival (78.87%) compared to semustine (Me-CCNU) (55.88%), indicating its superior efficacy.
TMZ also had a lower rate of adverse events (29.11%) compared to Me-CCNU (45.15%), suggesting that TMZ is not only more effective but also has a better safety profile for treating these types of brain tumors.
[Multicenter randomized controlled study of temozolomide versus semustine in the treatment of recurrent malignant glioma].Sun, J., Yang, XJ., Yang, SY.[2018]
In a study involving 97 patients with malignant gliomas, temozolomide (TMZ) demonstrated a significantly higher response rate (35.71%) compared to lomustine (CCNU) (9.09%), indicating its greater efficacy in treating these aggressive brain tumors.
TMZ was found to have an acceptable safety profile, with common side effects being mild nausea and vomiting, suggesting it could be a preferred chemotherapy option for patients with refractory malignant brain gliomas.
[A multicenter randomized controlled study of temozolomide in 97 patients with malignant brain glioma].Qian, ZZ., Wang, HQ., Liu, XM., et al.[2018]
In a pilot study involving 29 patients with newly diagnosed anaplastic astrocytoma, the combination of carmustine and temozolomide with radiotherapy showed significant hematologic and pulmonary toxicities, leading to dose reductions in over 70% of patients in one treatment arm.
Due to the poor tolerance of the combination therapy, future studies will focus on comparing single-agent carmustine versus single-agent temozolomide, indicating a shift towards safer treatment options for brain tumors.
Phase I study pilot arms of radiotherapy and carmustine with temozolomide for anaplastic astrocytoma (Radiation Therapy Oncology Group 9813): implications for studies testing initial treatment of brain tumors.Chang, SM., Seiferheld, W., Curran, W., et al.[2018]

References

[Multicenter randomized controlled study of temozolomide versus semustine in the treatment of recurrent malignant glioma]. [2018]
[A multicenter randomized controlled study of temozolomide in 97 patients with malignant brain glioma]. [2018]
[Comparison of two regimens of postoperative concurrent chemoradiotherapy in adult patients with grade III-IV cerebral gliomas]. [2018]
Sequential administration of temozolomide and fotemustine: depletion of O6-alkyl guanine-DNA transferase in blood lymphocytes and in tumours. [2020]
Phase I study pilot arms of radiotherapy and carmustine with temozolomide for anaplastic astrocytoma (Radiation Therapy Oncology Group 9813): implications for studies testing initial treatment of brain tumors. [2018]
Temozolomide in combination with BCNU before and after radiotherapy in patients with inoperable newly diagnosed glioblastoma multiforme. [2022]
Phase 1 study of 28-day, low-dose temozolomide and BCNU in the treatment of malignant gliomas after radiation therapy. [2018]
A Pilot Study (SWOG S0429) of Weekly Cetuximab and Chest Radiotherapy for Poor-Risk Stage III Non-Small Cell Lung Cancer. [2023]
Scheduling of chemotherapy and radiotherapy in locally advanced non-small cell lung cancer. [2019]
10.United Statespubmed.ncbi.nlm.nih.gov
Phase II Trial of Cetuximab and Conformal Radiotherapy Only in Locally Advanced Pancreatic Cancer with Concurrent Tissue Sampling Feasibility Study. [2021]
11.United Statespubmed.ncbi.nlm.nih.gov
Preclinical Data on Efficacy of 10 Drug-Radiation Combinations: Evaluations, Concerns, and Recommendations. [2020]
12.United Statespubmed.ncbi.nlm.nih.gov
Induction Chemotherapy Followed by Cetuximab Radiotherapy Is Not Superior to Concurrent Chemoradiotherapy for Head and Neck Carcinomas: Results of the GORTEC 2007-02 Phase III Randomized Trial. [2022]
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