EF-41/KEYNOTE-D58Trial

JRCT ID: jRCT2011240045

Registered date:23/10/2024

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Newly Diagnosed Glioblastoma
• Date of first enrollment: 23/10/2024
• Target sample size: 741
• Countries of recruitment: America,Japan,United Kingdom,Japan,Switzerland,Japan,Spain,Japan,Poland,Japan,Italy,Japan,Israel,Japan,Germany,Japan,France,Japan,Czech,Japan,Canada,Japan
• Study type: Interventional

Intervention(s)

Study intervention(s) will be administered by the investigator and/or study staff according to the specifications within the Pharmacy Manual.
The treatment(s) to be used in this study are outlined below:
Pembrolizumab (MK-3475) or Placebo
Pembrolizumab or placebo dose throughout this study is 200 mg IV Q3W for a maximum of 35 cycles. The placebo solution which will be used in this study is saline solution for infusion and it will be provided centrally to the study site.
NovoTTF-100A System
TTFields therapy at 200 kHz will be provided using the NovoTTF-100A System, also known as NovoTTF-100A System (G2 System),with maximal intensity of 707mA (RMS) in two sequential, perpendicular field directions. The therapy will be continues, 18 hours per day (monthly average) and up to 24 months.
Temozolomide
Maintenance TMZ treatment will be administered as standard of care, at dosing regimen of 150-200 mg2 PO for 5 days, every 28 days. Administration and dosing guidelines are available from the manufacturer and are summarized in the TMZ package insert.

Outcome(s)

Primary Outcome

OS will serve as primary efficacy endpoint in this study.
OS is defined as the time from randomization to death due to any cause.

Secondary Outcome

Progression-Free Survival per mRANO assessed by investigator
Progression-Free Survival per RANO assessed by investigator
Progression-Free Survival at 6 and 12 Months
Next Progression-free survival (PFS2)
1- and 2-Year Survival Rates

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

1. The participant (or legally acceptable representative) has provided documented informed consent for the study.
2. Be > 18 years of age on day of providing informed consent.
3. Participant with new diagnosis of GBM according to WHO 2021 Classification.
4. 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.
5. Have completed standard adjuvant chemoradiotherapy of RT according to local practice (56-64 Gy), and concomitant TMZ chemotherapy.
6. Able to start treatment at least 4 weeks from the later of last dose of concomitant temozolomide or radiotherapy.
7. Amenable to treatment with NovoTTF-100A System concomitant with maintenance temozolomide (150-200 mg/m2 daily x 5, Q28 days).
8. All patients must have had tissue submitted for MGMT Promoter Methylation determination prior to randomization.
9. Have an ECOG Performance Status of 0 to 1 assessed within 7 days before randomization.
10. Life expectancy > 3 months.
11. Stable or decreasing dose of corticosteroids (dexamethasone < 2mg or equivalent) for the last 7 days prior to randomization, if applicable.
12. Have adequate organ function as defined in the following table. Specimens must be collected within 10 days prior to randomization.
13. 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:
14. 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 protocal.
15. Able to have MRI with contrast of the brain.

Exclude criteria

1. 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).
2. Ongoing requirement for >2 mg dexamethasone (or equivalent), due to intracranial mass effect.
3. 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.
4. 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
5. 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.
6. 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.
7. 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.
8. Has severe hypersensitivity (>Grade 3) to the experimental drug and/or any of its excipients.
9. 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.
10. Has a history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
11. Has an active infection requiring systemic therapy.
12. 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:
Known history of HBV and HCV infection
As mandated by local health authority
13. 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.
14. Has a known psychiatric or substance abuse disorder that would interfere with the participants ability to cooperate with the requirements of the study.
15. Has had an allogenic tissue/solid organ transplant.
16. Early progressive disease after the end of TMZ/RT. If pseudoprogression is suspected, additional imaging studies should be performed to rule out true progression.
17. Infratentorial or leptomeningeal disease.
18. Implanted pacemaker, defibrillator, deep brain stimulator, other implanted electronic devices in the brain, or documented clinically significant arrhythmias.
19. A skull defect (such as, missing bone with no replacement) or bullet fragments.
20. Evidence of increased intracranial pressure (midline shift > 5mm, clinically significant papilledema, vomiting and nausea or reduced level of consciousness).
21. Known allergies to medical adhesives or hydrogel and/or compounds of similar chemical or biologic composition to Temozolomide.
22. Admitted to an institution by administrative or court order.

Related Information

• Primary Sponsor: Azuma Hisaya