Please note that the copy function is not enabled for this field.
If you wish to
modify
existing outcomes, please copy and paste the current outcome text into the Update field.
LOGIN
CREATE ACCOUNT
LOGIN
CREATE ACCOUNT
MY TRIALS
REGISTER TRIAL
FAQs
HINTS AND TIPS
DEFINITIONS
Trial Review
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this
information for consumers
Download to PDF
Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/ct2/show/NCT04195139
Registration number
NCT04195139
Ethics application status
Date submitted
18/11/2019
Date registered
11/12/2019
Date last updated
15/06/2023
Titles & IDs
Public title
Nivolumab and Temozolomide Versus Temozolomide Alone in Newly Diagnosed Elderly Patients With GBM
Query!
Scientific title
A Randomised Phase II Study of NivolUmab and TeMozolomide vs Temozolomide Alone in Newly Diagnosed Elderly Patients With Glioblastoma (NUTMEG)
Query!
Secondary ID [1]
0
0
ACTRN12617000267358
Query!
Secondary ID [2]
0
0
COGNO 16/01, CTC 0156
Query!
Universal Trial Number (UTN)
Query!
Trial acronym
NUTMEG
Query!
Linked study record
Query!
Health condition
Health condition(s) or problem(s) studied:
Glioblastoma Multiforme
0
0
Query!
Condition category
Condition code
Cancer
0
0
0
0
Query!
Brain
Query!
Intervention/exposure
Study type
Interventional
Query!
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.
Query!
Intervention code [1]
0
0
Treatment: Drugs
Query!
Comparator / control treatment
Query!
Control group
Query!
Outcomes
Primary outcome [1]
0
0
Overall survival outcomes
Query!
Assessment method [1]
0
0
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.
Query!
Timepoint [1]
0
0
24 months post randomisation of first participant
Query!
Secondary outcome [1]
0
0
Progression Free Survival
Query!
Assessment method [1]
0
0
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.
Query!
Timepoint [1]
0
0
6 months post randomisation
Query!
Secondary outcome [2]
0
0
Number and severity of adverse events
Query!
Assessment method [2]
0
0
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.
Query!
Timepoint [2]
0
0
Through study completion, up to 24 months
Query!
Secondary outcome [3]
0
0
Health related quality of life of participants (QLQ C-30)
Query!
Assessment method [3]
0
0
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.
Query!
Timepoint [3]
0
0
Through study completion, up to 24 months
Query!
Secondary outcome [4]
0
0
Health related quality of life of participants (QLQ-BN20)
Query!
Assessment method [4]
0
0
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.
Query!
Timepoint [4]
0
0
Through study completion, up to 24 months
Query!
Secondary outcome [5]
0
0
Health related quality of life of participants (EuroQoL EQ-5D-5L)
Query!
Assessment method [5]
0
0
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).
Query!
Timepoint [5]
0
0
Through study completion, up to 24 months
Query!
Secondary outcome [6]
0
0
Neurologic function of participants
Query!
Assessment method [6]
0
0
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.
Query!
Timepoint [6]
0
0
Through study completion, up to 24 months
Query!
Secondary outcome [7]
0
0
Correlating modified RANO and immune related RANO in the experimental arm
Query!
Assessment method [7]
0
0
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).
Query!
Timepoint [7]
0
0
Through study completion, up to 24 months
Query!
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
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
Query!
Minimum age
65
Years
Query!
Query!
Maximum age
No limit
Query!
Query!
Sex
Both males and females
Query!
Can healthy volunteers participate?
No
Query!
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. 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.
Query!
Study design
Purpose of the study
Treatment
Query!
Allocation to intervention
Randomised controlled trial
Query!
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Query!
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Query!
Masking / blinding
Open (masking not used)
Query!
Who is / are masked / blinded?
Query!
Query!
Query!
Query!
Intervention assignment
Parallel
Query!
Other design features
Query!
Phase
Phase 2
Query!
Type of endpoint/s
Query!
Statistical methods / analysis
Query!
Recruitment
Recruitment status
Active, not recruiting
Query!
Data analysis
Query!
Reason for early stopping/withdrawal
Query!
Other reasons
Query!
Date of first participant enrolment
Anticipated
Query!
Actual
22/02/2018
Query!
Date of last participant enrolment
Anticipated
Query!
Actual
Query!
Date of last data collection
Anticipated
31/12/2025
Query!
Actual
Query!
Sample size
Target
Query!
Accrual to date
Query!
Final
103
Query!
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,TAS,VIC,WA
Query!
Recruitment hospital [1]
0
0
Campbelltown Hospital - Campbelltown
Query!
Recruitment hospital [2]
0
0
Chris O'Brien Lifehouse - Camperdown
Query!
Recruitment hospital [3]
0
0
Gosford Hospital - Gosford
Query!
Recruitment hospital [4]
0
0
Newcastle Private Hospital - New Lambton Heights
Query!
Recruitment hospital [5]
0
0
Port Macquarie Hospital - Port Macquarie
Query!
Recruitment hospital [6]
0
0
Prince of Wales Hospital - Randwick
Query!
Recruitment hospital [7]
0
0
Royal North Shore Hospital - Saint Leonards
Query!
Recruitment hospital [8]
0
0
Wollongong Hospital - Wollongong
Query!
Recruitment hospital [9]
0
0
Royal Brisbane and Women's Hospital - Herston
Query!
Recruitment hospital [10]
0
0
Icon Cancer Centre - South Brisbane
Query!
Recruitment hospital [11]
0
0
Princess Alexandra Hospital - Woolloongabba
Query!
Recruitment hospital [12]
0
0
Royal Adelaide Hospital - Adelaide
Query!
Recruitment hospital [13]
0
0
Flinders Medical Centre - Bedford Park
Query!
Recruitment hospital [14]
0
0
Royal Hobart Hospital - Hobart
Query!
Recruitment hospital [15]
0
0
Monash Medical Centre - Clayton
Query!
Recruitment hospital [16]
0
0
Austin Hospital - Heidelberg
Query!
Recruitment hospital [17]
0
0
Peter MacCallum Cancer Centre - Melbourne
Query!
Recruitment hospital [18]
0
0
Epworth Healthcare - Richmond
Query!
Recruitment hospital [19]
0
0
Sir Charles Gairdner Hospital - Nedlands
Query!
Recruitment postcode(s) [1]
0
0
2560 - Campbelltown
Query!
Recruitment postcode(s) [2]
0
0
2050 - Camperdown
Query!
Recruitment postcode(s) [3]
0
0
2250 - Gosford
Query!
Recruitment postcode(s) [4]
0
0
2305 - New Lambton Heights
Query!
Recruitment postcode(s) [5]
0
0
2444 - Port Macquarie
Query!
Recruitment postcode(s) [6]
0
0
2031 - Randwick
Query!
Recruitment postcode(s) [7]
0
0
2065 - Saint Leonards
Query!
Recruitment postcode(s) [8]
0
0
2500 - Wollongong
Query!
Recruitment postcode(s) [9]
0
0
4029 - Herston
Query!
Recruitment postcode(s) [10]
0
0
4101 - South Brisbane
Query!
Recruitment postcode(s) [11]
0
0
4102 - Woolloongabba
Query!
Recruitment postcode(s) [12]
0
0
5000 - Adelaide
Query!
Recruitment postcode(s) [13]
0
0
5042 - Bedford Park
Query!
Recruitment postcode(s) [14]
0
0
7000 - Hobart
Query!
Recruitment postcode(s) [15]
0
0
3168 - Clayton
Query!
Recruitment postcode(s) [16]
0
0
3084 - Heidelberg
Query!
Recruitment postcode(s) [17]
0
0
3000 - Melbourne
Query!
Recruitment postcode(s) [18]
0
0
3121 - Richmond
Query!
Recruitment postcode(s) [19]
0
0
6009 - Nedlands
Query!
Recruitment outside Australia
Country [1]
0
0
United States of America
Query!
State/province [1]
0
0
North Carolina
Query!
Funding & Sponsors
Primary sponsor type
Other
Query!
Name
University of Sydney
Query!
Address
Query!
Country
Query!
Other collaborator category [1]
0
0
Other
Query!
Name [1]
0
0
Cooperative Trials Group for Neuro-Oncology
Query!
Address [1]
0
0
Query!
Country [1]
0
0
Query!
Ethics approval
Ethics application status
Query!
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.
Query!
Trial website
https://clinicaltrials.gov/ct2/show/NCT04195139
Query!
Trial related presentations / publications
Query!
Public notes
Query!
Contacts
Principal investigator
Name
0
0
Mustafa Khasraw
Query!
Address
0
0
Duke University
Query!
Country
0
0
Query!
Phone
0
0
Query!
Fax
0
0
Query!
Email
0
0
Query!
Contact person for public queries
Name
0
0
Query!
Address
0
0
Query!
Country
0
0
Query!
Phone
0
0
Query!
Fax
0
0
Query!
Email
0
0
Query!
Contact person for scientific queries
Summary Results
For IPD and results data, please see
https://clinicaltrials.gov/ct2/show/NCT04195139
Download to PDF