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Glioma

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Temozolomide

Nivolumab

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Immune Checkpoint Inhibitors

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Alkylating Agents

Mace

Nutmeg

After radiotherapy and 4 week break, participants who are assigned to this arm will receive Nivolumab with concurrent adjuvant temozolomide treatment

After radiotherapy and 4 week break, participants who are assigned to this arm will receive the standard treatment of adjuvant temozolomide treatment

Participants will receive Nivolumab intravenous infusions (240 mg days 1 and 15 every 28 days for cycles 1-4; then 480 mg day 1 every 28 days for cycles 5-6).

Participants will receive temozolomide (TMZ) tablets days 1-5, every 28 days for 6 cycles. TMZ will be dosed at 150mg/m2 for the first cycle. If well tolerated TMZ is then given at 200mg/m2 for cycles 2 - 6.

Mustafa Khasraw

This study aims to investigate effect of Nivolumab and Temozolomide vs Temozolomide alone on overall survival in newly diagnosed elderly patients with glioblastoma.

Who is it for? You may be eligible to join this study if you are aged 65 years or above, with newly diagnosed histologically confirmed GBM (WHO grade IV glioma including gliosarcoma) following surgery.

The study aims to evaluate whether the combination of adjuvant nivolumab with temozolomide improves overall survival outcomes for this patient population. The outcome of the study will help determine the most effective treatment for patients with glioblastoma in the future.

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).

All participants will receive radiotherapy (weekdays over 21 days) concurrently with temozolomide (TMZ) tablets 75mg/m2 daily for 21 days.

After a 4 week break, participants will receive either experimental or standard treatment.

Experimental treatment: Participants assigned to this group will receive nivolumab intravenous infusions (days 1 and 15 every 28 days with concurrent adjuvant temozolomide tablets days 1-5, every 28 days) for 6 cycles.

Standard treatment: Participants assigned to this group will receive the standard treatment of adjuvant temozolomide (days 1-5 every 28 days) for 6 cycles.

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

A Randomised Phase II Study of NivolUmab and TeMozolomide vs Temozolomide Alone in Newly Diagnosed Elderly Patients With Glioblastoma (NUTMEG)

Overall survival is defined as the interval from the date of randomisation to date of death from any cause, or date of last known follow-up alive. This will be calculated using the Kaplan-Meier method.

Progression free survival (PFS) is defined as the interval from date of randomisation to the date of first evidence of disease progression or death from any cause, whichever occurs first. The PFS will be calculated using the Kaplan-Meier method and disease progression is defined according to modified Response Assessment in Neuro-Oncology (RANO) criteria.

The NCI Common Terminology Criteria for Adverse Events version 4.03 (NCI CTCAE v4.03) will be used to classify and grade the intensity of adverse events.

Health related quality of life will be reported directly by the participants using the EORTC core quality of life questionnaire QLQ C-30. The QLQ-C30 is a 30-item questionnaire with 5 functional scales (physical, role, cognitive, emotional, and social), global health status, 3 symptom scales (fatigue, pain, nausea/vomiting), and other (dyspnoea, appetite loss, insomnia, constipation/diarrhea, and financial difficulties). Most questions used 4-point scale (1 'Not at All' to 4 'Very Much'); 2 questions used 7-point scale (1 'Very Poor' to 7 'Excellent'). Scores are averaged and transformed to 0-100 scale; higher score=better level of physical functioning.

Health related quality of life will be reported directly by the participants using the EORTC core quality of life questionnaire brain cancer specific module (QLQ-BN20). The QLQ-BN20 consisted of 20 items assessing visual disorders, motor dysfunction, communication deficit, various disease symptoms (e.g. headaches and seizures), treatment toxicities (e.g. hair loss) and future uncertainty. All of the 20 items are rated on a 4 point scale (1=not at all, 4=very much), and were linearly transformed to a 0-100 scale, with higher scores indicating more severe symptoms.

Health related quality of life will be reported directly by the participants using the EORTC core quality of life questionnaire EuroQol EQ-5D-5L. The EQ-5D-5L descriptive system comprises the following 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression and as overall health using a "thermometer" visual analog scale with response options ranging from 0 (worst imaginable health) to 100 (best imaginable health).

Cognitive function will be assessed by the Neurologic Assessment in Neuro-Oncology (NANO) scales. The NANO is a quantifiable evaluation of nine major domains for subjects with brain tumours. The domains include: gait, strength, ataxia, sensation, visual field, facial strength, language, level of consciousness, behaviour and overall. Each domain is rated on a scale of 0 to 3 where 0 represents normal and 3 represents the worst severity. The evaluation is based on direct observation/testing performed during routine office visits.

Site investigators will assess disease progression using modified RANO criteria for clinical decision making. The study team will coordinate image analysis and central review of MRI including modified RANO (both experimental and comparator arms) and iRANO (in the experimental arm).

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Nivolumab and Temozolomide Versus Temozolomide Alone in Newly Diagnosed Elderly Patients With GBM	NCT04195139	Glioblastoma Mu...	Nivolumab Temozolomide	65 Years -	University of Sydney
Nivolumab and Temozolomide Versus Temozolomide Alone in Newly Diagnosed Elderly Patients With GBM	NCT04195139	Glioblastoma Mu...	Nivolumab Temozolomide	65 Years -	University of Sydney

Spots Global Cancer Trial Database for astrocytoma who grade iv