Clinical trial NCT04195139: Nivolumab and Temozolomide Versus Temozolomide Alone in Newly Diagnosed Elderly Patients With GBM
Official title: A Randomised Phase II Study of NivolUmab and TeMozolomide vs Temozolomide Alone in Newly Diagnosed Elderly Patients With Glioblastoma (NUTMEG)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Glioblastoma Multiforme
Keywords: GBM
Astrocytoma WHO grade IV
Elderly
Nivolumab
Temozolomide
Lead sponsor: University of Sydney
Sponsor class: OTHER
Collaborators: name: Cooperative Trials Group for Neuro-Oncology
First posted: 2019-12-11
Enrollment: 103
Sex: ALL
Minimum age (years): 65
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 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.
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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).

Eligibility criteria: Inclusion Criteria:

1. 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
2. Tissue available for MGMT testing
3. ECOG 0-2
4. Life expectancy of \>12 weeks
5. Adequate bone marrow function (platelets \> 100 x 10\^9/L, ANC \> 1.5 x 10\^9/L)
6. Adequate liver function (ALT/AST \< 1.5 x ULN)
7. Adequate renal function (creatinine clearance \> 30 ml/min measured using Cockcroft-Gault
8. Willing and able to comply with all study requirements, including treatment, timing and/or nature of required assessments including MRI
9. Signed, written informed consent

Exclusion Criteria:

1. Specific comorbidities or conditions (e.g. psychiatric) or concomitant medications which may impact with the administration of study related treatments or procedures
2. Other co-morbidities or conditions that may compromise assessment of key outcomes
3. Prior chemotherapy or cranial radiation within the last 5 years. Prior or concomitant therapies for GBM (except surgery).
4. 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.
5. Significant infection, including chronic active hepatitis B, hepatitis C, or HIV. Testing for these is not mandatory unless clinically indicated
6. 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.
7. 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.
8. 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.

Primary outcomes:
measure: Overall survival outcomes
timeFrame: 24 months post randomisation of first participant
Secondary outcomes:
measure: Progression Free Survival
timeFrame: 6 months post randomisation
measure: Number and severity of adverse events
timeFrame: Through study completion, up to 24 months
measure: Health related quality of life of participants (QLQ C-30)
timeFrame: Through study completion, up to 24 months
measure: Health related quality of life of participants (QLQ-BN20)
timeFrame: Through study completion, up to 24 months
measure: Health related quality of life of participants (EuroQoL EQ-5D-5L)
timeFrame: Through study completion, up to 24 months
measure: Neurologic function of participants
timeFrame: Through study completion, up to 24 months
measure: Correlating modified RANO and immune related RANO in the experimental arm
timeFrame: Through study completion, up to 24 months
Other outcomes:
Locations:
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Campbelltown
country: Australia
facility: Campbelltown Hospital
state: New South Wales
city: Camperdown
country: Australia
facility: Chris O'Brien Lifehouse
state: New South Wales
city: Gosford
country: Australia
facility: Gosford Hospital
state: New South Wales
city: New Lambton Heights
country: Australia
facility: Newcastle Private Hospital
state: New South Wales
city: Port Macquarie
country: Australia
facility: Port Macquarie Hospital
state: New South Wales
city: Randwick
country: Australia
facility: Prince of Wales Hospital
state: New South Wales
city: Saint Leonards
country: Australia
facility: Royal North Shore Hospital
state: New South Wales
city: Wollongong
country: Australia
facility: Wollongong Hospital
state: New South Wales
city: Herston
country: Australia
facility: Royal Brisbane and Women's Hospital
state: Queensland
city: South Brisbane
country: Australia
facility: Icon Cancer Centre
state: Queensland
city: Woolloongabba
country: Australia
facility: Princess Alexandra Hospital
state: Queensland
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
state: South Australia
city: Bedford Park
country: Australia
facility: Flinders Medical Centre
state: South Australia
city: Hobart
country: Australia
facility: Royal Hobart Hospital
state: Tasmania
city: Clayton
country: Australia
facility: Monash Medical Centre
state: Victoria
city: Heidelberg
country: Australia
facility: Austin Hospital
state: Victoria
city: Melbourne
country: Australia
facility: Peter MacCallum Cancer Centre
state: Victoria
city: Richmond
country: Australia
facility: Epworth Healthcare
state: Victoria
city: Nedlands
country: Australia
facility: Sir Charles Gairdner Hospital
state: Western Australia
Study officials:
affiliation: Duke University
name: Mustafa Khasraw
role: STUDY_CHAIR
References: