Nivolumab and Temozolomide Versus Temozolomide Alone in Newly Diagnosed Elderly Patients With GBM

Study details:

Participants will be allocated to either experimental or control group in a 2:1 ratio by chance (randomly). Patients assigned to the experimental group will receive a course of nivolumab via intravenous infusion (240 mg on days 1 and 15 every 28 days for cycles 1-4; then 480 mg day 1 every 28 days for cycles 5-6) in addition to the standard regimen of Temozolomide (TMZ) tablets and radiotherapy. Patients assigned to the control group will receive the standard treatment of adjuvant temozolomide (150-200mg/m2 days 1-5 every 28 days) for 6 cycles and standard radiotherapy treatment (40 Gy administered in 15 fractions).

Inclusion criteria

• Adults, aged greater than or equal to 70 years, or aged 65-69 years if long course RT is inappropriate, with newly diagnosed histologically confirmed GBM (WHO grade IV glioma including gliosarcoma) following surgery
• Tissue available for MGMT testing
• ECOG 0-2
• Life expectancy of >12 weeks
• Adequate bone marrow function (platelets > 100 x 10^9/L, ANC > 1.5 x 10^9/L)
• Adequate liver function (ALT/AST < 1.5 x ULN)
• Adequate renal function (creatinine clearance > 30 ml/min measured using Cockcroft-Gault
• Willing and able to comply with all study requirements, including treatment, timing and/or nature of required assessments including MRI
• Signed, written informed consent

Exclusion criteria

• Specific comorbidities or conditions (e.g. psychiatric) or concomitant medications which may impact with the administration of study related treatments or procedures
• Other co-morbidities or conditions that may compromise assessment of key outcomes
• Prior chemotherapy or cranial radiation within the last 5 years. Prior or concomitant therapies for GBM (except surgery).
• History of another malignancy within 2 years prior to registration. Patients with a past history of adequately treated carcinoma-in-situ, basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or superficial transitional cell carcinoma of the bladder are eligible. Patients with a history of other malignancies are eligible if they have been continuously disease free for at least 2 years after definitive primary treatment.
• Significant infection, including chronic active hepatitis B, hepatitis C, or HIV. Testing for these is not mandatory unless clinically indicated
• Active, known or suspected autoimmune disease. Subjects with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
• For symptoms related to GBM, the need for >4 mg/day of dexamethasone or >20 mg/day prednisone (or equivalent) at the time of screening.
• For a condition other than GBM, the need for >2 mg/day of dexamethasone or >10 mg/day prednisone (or equivalent) or other immunosuppressive medications within 14 days prior to randomisation. Exceptions to this include the use of inhaled or topical steroids >10 mg/day prednisone (or equivalent), which are permitted in the absence of active autoimmune disease.