IRB Study Number 25-004
Status Recruiting
Institute Taussig Cancer Institute
Description
Primary Objective
To compare overall survival (OS) for subjects treated with Optune concomitant with maintenance temozolomide (TMZ) plus pembrolizumab versus those treated with Optune concomitant with maintenance TMZ plus placebo
Secondary Objectives
To evaluate progression-free survival (PFS) per modified response assessment in neuro-oncology criteria (mRANO) as assessed locally by the investigator for subjects treated with Optune concomitant with maintenance TMZ plus pembrolizumab versus those treated with Optune concomitant with maintenance TMZ plus placebo
To evaluate PFS per response assessment in neuro-oncology criteria (RANO) as assessed locally by the investigator for subjects treated with Optune concomitant with maintenance TMZ plus pembrolizumab versus those treated with Optune concomitant with maintenance TMZ plus placebo
To evaluate PFS rate at 6 months (PFS6m) and at 12 months (PFS12 m) per mRANO as assessed locally by the investigator.
To evaluate next PFS (PFS2) per mRANO as assessed locally by the investigator.
To evaluate 1- and 2-year survival rates
To evaluate changes in Health-Related Quality of Life (HRQoL) assessment using the European Organization for the Research and Treatment of Cancer (EORTC) QLQ-C30 with BN20 module
To evaluate the severity and tolerability by the proportion of adverse events (AEs)
Inclusion Criteria
The participant (or legally acceptable representative) has provided documented informed consent for the study.
Be ≥ 18 years of age on day of providing informed consent.
Participant with new diagnosis of GBM according to WHO 2021 Classification.
Recovered from maximal debulking surgery (gross total resection, partial resection and biopsy-only patients are all acceptable), Gliadel wafers placement at the time of surgical resection is allowed.
Have completed standard adjuvant chemoradiotherapy of RT according to local practice (56-64 Gy), and concomitant TMZ chemotherapy.
Able to start treatment at least 4 weeks from the later of last dose of concomitant temozolomide or radiotherapy.
Amenable to treatment with Optune concomitant with maintenance temozolomide (150-200 mg/m^2 daily x 5, Q28 days).
All patients must have had tissue submitted for MGMT Promoter Methylation determination prior to randomization.
Have an ECOG Performance Status of 0 to 1 assessed within 7 days before randomization.
Life expectancy ≥ 3 months.
Stable or decreasing dose of corticosteroids (dexamethasone ≤ 2mg or equivalent) for the last 7 days prior to randomization, if applicable.
Have adequate organ function as defined in the following table. Specimens must be collected within 10 days prior to randomization.
A male participant is eligible to participate if he agrees to the following during the intervention period and for at least the time needed to eliminate each study intervention after the last dose of study intervention. The length of time required to continue contraception for each study intervention is as follows:
TMZ: 95 days
• Refrains from donating sperm PLUS either:
• Abstains from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis) and agrees to remain abstinent OR
• Uses contraception unless confirmed to be azoospermic (vasectomized or secondary to medical cause, documented from the site personnel's review of the participant's medical records, medical examination, or medical history interview) as detailed below:
-Uses a male condom plus partner use of an additional contraceptive method when having penile-vaginal intercourse with a WOCBP who is not currently pregnant. Note: Men with a pregnant or breastfeeding partner must agree to remain abstinent from penile-vaginal intercourse or use a male condom during each episode of penile-vaginal penetration.
-Contraceptive use by men should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. If the contraception requirements in the local label for any of the study interventions is more stringent than the requirements above, the local label requirements are to be followed.
- A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies:
a. Not a woman of childbearing potential (WOCBP)
b. Is a WOCBP and:
- Uses a contraceptive method that is highly effective (with a failure rate of <1% per year), with low user dependency, or be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis), as described in Appendix 1 during the intervention period and for at least the time needed to eliminate each study intervention after the last dose of study intervention and agrees not to donate eggs (ova, oocytes) to others or freeze/store for her own use for the purpose of reproduction during this period. The length of time required to continue contraception for each study intervention is as follows:
TMZ: 180 days
Pembrolizumab: 120 days
The investigator should evaluate the potential for contraceptive method failure (i.e., noncompliance, recently initiated) in relationship to the first dose of study intervention. Contraceptive use by women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. If the contraception requirements in the local label for any of the study interventions is more stringent than the requirements above, the local label requirements are to be followed.
Has a negative highly sensitive pregnancy test (urine or serum as required by local regulations) within 24 hours for urine or within 72 hours for serum before the first dose of study intervention. If a urine test cannot be confirmed OR
• Uses contraception unless confirmed to be azoospermic (vasectomized or secondary to medical cause, documented from the site personnel's review of the participant's medical records, medical examination, or medical history interview) as detailed below:
-Uses a male condom plus partner use of an additional contraceptive method when having penile-vaginal intercourse with a WOCBP who is not currently pregnant. Note: Men with a pregnant or breastfeeding partner must agree to remain abstinent from penile-vaginal intercourse or use a male condom during each episode of penile-vaginal penetration.
-Contraceptive use by men should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. If the contraception requirements in the local label for any of the study interventions is more stringent than the requirements above, the local label requirements are to be followed.
- A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies:
a. Not a woman of childbearing potential (WOCBP)
b. Is a WOCBP and:
- Uses a contraceptive method that is highly effective (with a failure rate of <1% per year), with low user dependency, or be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis), as described in Appendix 1 during the intervention period and for at least the time needed to eliminate each study intervention after the last dose of study intervention and agrees not to donate eggs (ova, oocytes) to others or freeze/store for her own use for the purpose of reproduction during this period. The length of time required to continue contraception for each study intervention is as follows:
TMZ: 180 days
Pembrolizumab: 120 days
The investigator should evaluate the potential for contraceptive method failure (i.e., noncompliance, recently initiated) in relationship to the first dose of study intervention. Contraceptive use by women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. If the contraception requirements in the local label for any of the study interventions is more stringent than the requirements above, the local label requirements are to be followed.
Has a negative highly sensitive pregnancy test (urine or serum as required by local regulations) within 24 hours for urine or within 72 hours for serum before the first dose of study intervention. If a urine test cannot be confirmed
Exclusion Criteria
Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g., CTLA-4, OX 40, CD137).
Ongoing requirement for >2 mg dexamethasone (or equivalent), due to intracranial mass effect.
Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks prior to randomization. Note: Participants must have recovered from all AEs due to previous therapies to ≤Grade 1 or baseline. Participants with ≤Grade 2 neuropathy may be eligible. Participants with endocrine-related AEs Grade ≤2 requiring treatment or hormone replacement may be eligible. Note: If the participant had a major operation, the participant must have recovered adequately from the procedure and/or any complications from the operation before starting study intervention.
Received a live or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines are allowed.
Refer to Section 6.5.1 for information on COVID-19 vaccines
Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first study treatment. Note: Participants who have entered the follow-up phase of an investigational study may participate as long as it has been 4 weeks after the last dose of the previous investigational agent.
Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of study medication.
Has a known additional malignancy that is progressing or has required active treatment within the past 3 years.
Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g., breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded.
Has severe hypersensitivity (≥Grade 3) to the experimental drug and/or any of its excipients.
Has an active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed.
Has a history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
Has an active infection requiring systemic therapy.
Has a known history of human immunodeficiency virus (HIV), Hepatitis B (defined as HBsAg reactive) or known active Hepatitis C virus (defined as HCV RNA [qualitative] is detected) infection Note: Hepatitis B and C screening tests are not required unless:
O Known history of HBV and HCV infection
O As mandated by local health authority
Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not in the best interest of the participant to participate, in the opinion of the treating investigator.
Has a known psychiatric or substance abuse disorder that would interfere with the participant’s ability to cooperate with the requirements of the study.
Has had an allogenic tissue/solid organ transplant.
Early progressive disease after the end of TMZ/RT. If pseudoprogression is suspected, additional imaging studies should be performed to rule out true progression.
Infratentorial or leptomeningeal disease.
Implanted pacemaker, defibrillator, deep brain stimulator, other implanted electronic devices in the brain, or documented clinically significant arrhythmias.
A skull defect (such as, missing bone with no replacement) or bullet fragments.
Evidence of increased intracranial pressure (midline shift > 5mm, clinically significant papilledema, vomiting and nausea or reduced level of consciousness).
Known allergies to medical adhesives or hydrogel and/or compounds of similar chemical or biologic composition to Temozolomide.
Admitted to an institution by administrative or court order.
