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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT04195139




Registration number
NCT04195139
Ethics application status
Date submitted
18/11/2019
Date registered
11/12/2019
Date last updated
11/12/2019

Titles & IDs
Public title
Nivolumab and Temozolomide Versus Temozolomide Alone in Newly Diagnosed Elderly Patients With GBM
Scientific title
A Randomised Phase II Study of NivolUmab and TeMozolomide vs Temozolomide Alone in Newly Diagnosed Elderly Patients With Glioblastoma (NUTMEG)
Secondary ID [1] 0 0
ACTRN12617000267358
Secondary ID [2] 0 0
COGNO 16/01, CTC 0156
Universal Trial Number (UTN)
Trial acronym
NUTMEG
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Glioblastoma Multiforme 0 0
Condition category
Condition code
Cancer 0 0 0 0
Brain

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Nivolumab
Treatment: Drugs - Temozolomide

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

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


Treatment: Drugs: Nivolumab
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).

Treatment: Drugs: Temozolomide
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.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Overall survival outcomes - 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.
Timepoint [1] 0 0
24 months post randomisation of first participant
Secondary outcome [1] 0 0
Progression Free Survival - 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.
Timepoint [1] 0 0
6 months post randomisation
Secondary outcome [2] 0 0
Number and severity of adverse events - 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.
Timepoint [2] 0 0
Through study completion, up to 24 months
Secondary outcome [3] 0 0
Health related quality of life of participants - 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.
Timepoint [3] 0 0
Through study completion, up to 24 months
Secondary outcome [4] 0 0
Health related quality of life of participants - 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.
Timepoint [4] 0 0
Through study completion, up to 24 months
Secondary outcome [5] 0 0
Health related quality of life of participants - 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).
Timepoint [5] 0 0
Through study completion, up to 24 months
Secondary outcome [6] 0 0
Neurologic function of participants - 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.
Timepoint [6] 0 0
Through study completion, up to 24 months
Secondary outcome [7] 0 0
Correlating modified RANO and immune related RANO in the experimental arm - 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).
Timepoint [7] 0 0
Through study completion, up to 24 months

Eligibility
Key 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
Cockroft-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
Minimum age
65 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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. A condition other than GBM, requiring systemic treatment with either corticosteroids
(> 10 mg daily prednisone or equivalent) or other immunosuppressive medications within
14 days prior to randomisation. Inhaled or topical steroids, and adrenal replacement
steroid doses > 10 mg daily prednisone or equivalent, are permitted in the absence of
active autoimmune disease.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,TAS,VIC,WA
Recruitment hospital [1] 0 0
Campbelltown Hospital - Campbelltown
Recruitment hospital [2] 0 0
Chris O'Brien Lifehouse - Camperdown
Recruitment hospital [3] 0 0
Gosford Hospital - Gosford
Recruitment hospital [4] 0 0
Newcastle Private Hospital - New Lambton Heights
Recruitment hospital [5] 0 0
Port Macquarie Hospital - Port Macquarie
Recruitment hospital [6] 0 0
Prince of Wales Hospital - Randwick
Recruitment hospital [7] 0 0
Royal North Shore Hospital - Saint Leonards
Recruitment hospital [8] 0 0
Wollongong Hospital - Wollongong
Recruitment hospital [9] 0 0
Royal Brisbane and Women's Hospital - Herston
Recruitment hospital [10] 0 0
Icon Cancer Centre - South Brisbane
Recruitment hospital [11] 0 0
Princess Alexandra Hospital - Woolloongabba
Recruitment hospital [12] 0 0
Royal Adelaide Hospital - Adelaide
Recruitment hospital [13] 0 0
Flinders Medical Centre - Bedford Park
Recruitment hospital [14] 0 0
Royal Hobart Hospital - Hobart
Recruitment hospital [15] 0 0
Monash Medical Centre - Clayton
Recruitment hospital [16] 0 0
Austin Hospital - Heidelberg
Recruitment hospital [17] 0 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment hospital [18] 0 0
Epworth Healthcare - Richmond
Recruitment hospital [19] 0 0
Sir Charles Gairdner Hospital - Nedlands
Recruitment postcode(s) [1] 0 0
2560 - Campbelltown
Recruitment postcode(s) [2] 0 0
2050 - Camperdown
Recruitment postcode(s) [3] 0 0
2250 - Gosford
Recruitment postcode(s) [4] 0 0
2305 - New Lambton Heights
Recruitment postcode(s) [5] 0 0
2444 - Port Macquarie
Recruitment postcode(s) [6] 0 0
2031 - Randwick
Recruitment postcode(s) [7] 0 0
2065 - Saint Leonards
Recruitment postcode(s) [8] 0 0
2500 - Wollongong
Recruitment postcode(s) [9] 0 0
4029 - Herston
Recruitment postcode(s) [10] 0 0
4101 - South Brisbane
Recruitment postcode(s) [11] 0 0
4102 - Woolloongabba
Recruitment postcode(s) [12] 0 0
5000 - Adelaide
Recruitment postcode(s) [13] 0 0
5042 - Bedford Park
Recruitment postcode(s) [14] 0 0
7000 - Hobart
Recruitment postcode(s) [15] 0 0
3168 - Clayton
Recruitment postcode(s) [16] 0 0
3084 - Heidelberg
Recruitment postcode(s) [17] 0 0
3000 - Melbourne
Recruitment postcode(s) [18] 0 0
3121 - Richmond
Recruitment postcode(s) [19] 0 0
6009 - Nedlands
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
North Carolina

Funding & Sponsors
Primary sponsor type
Other
Name
University of Sydney
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
Cooperative Trials Group for Neuro-Oncology
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Other
Name [2] 0 0
National Health and Medical Research Council, Australia
Address [2] 0 0
Country [2] 0 0

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/show/NCT04195139
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
NUTMEG Project Manager
Address 0 0
Country 0 0
Phone 0 0
+61 2 9562 5000
Fax 0 0
Email 0 0
nutmeg@ctc.usyd.edu.au
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT04195139