Glioblastoma MultiformePhase 2NUTMEGNCT04195139
Nivolumab and Temozolomide Versus Temozolomide Alone in Newly Diagnosed Elderly Patients With GBM
A Phase 2 study testing Nivolumab and Temozolomide in people with Glioblastoma Multiforme, run by University of Sydney at 20 sites in 2 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 65 years and older
- Conditions the study is for
- Glioblastoma Multiforme
- What is being tested?
- Nivolumab and Temozolomide
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 103 participants
- Where
- 20 sitesin 2 countries
- Study dates
- 22 Feb 2018to 31 Dec 2025
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 65 years and older
- All sexes
- No healthy volunteers
- Older adult
Who may be able to join
- 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)
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- 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
Who cannot join
- 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.
Trial locations and contacts
20 sites in 2 countries.
20 sites in 2 countries
Australia19 sites
Royal Adelaide Hospital
Adelaide, South Australia, 5000
Flinders Medical Centre
Bedford Park, South Australia, 5042
Campbelltown Hospital
Campbelltown, New South Wales, 2560
Chris O'Brien Lifehouse
Camperdown, New South Wales, 2050
Monash Medical Centre
Clayton, Victoria, 3168
Gosford Hospital
Gosford, New South Wales, 2250
Austin Hospital
Heidelberg, Victoria, 3084
Royal Brisbane and Women's Hospital
Herston, Queensland, 4029
Royal Hobart Hospital
Hobart, Tasmania, 7000
Peter MacCallum Cancer Centre
Melbourne, Victoria, 3000
Sir Charles Gairdner Hospital
Nedlands, Western Australia, 6009
Newcastle Private Hospital
New Lambton Heights, New South Wales, 2305
Port Macquarie Hospital
Port Macquarie, New South Wales, 2444
Prince of Wales Hospital
Randwick, New South Wales, 2031
Epworth Healthcare
Richmond, Victoria, 3121
Royal North Shore Hospital
Saint Leonards, New South Wales, 2065
Icon Cancer Centre
South Brisbane, Queensland, 4101
Wollongong Hospital
Wollongong, New South Wales, 2500
Princess Alexandra Hospital
Woolloongabba, Queensland, 4102
United States1 site
Duke University Medical Center
Durham, North Carolina, 27710
About this study
Official title: A Randomised Phase II Study of NivolUmab and TeMozolomide vs Temozolomide Alone in Newly Diagnosed Elderly Patients With Glioblastoma (NUTMEG)
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.
Read the 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).
- Conditions
- Glioblastoma Multiforme
- Being tested
- Nivolumab, Temozolomide
- Keywords
- GBM, Astrocytoma WHO grade IV, Elderly, Nivolumab, Temozolomide
- Medical subject headings
- Glioblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NivolumabDrug
Also called Opdivo
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).
TemozolomideDrug
Also called Temodar, Temodal, Temcad
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.
| Study group | Role | What they receive |
|---|---|---|
| Nivolumab and Temozolomide | Experimental | After radiotherapy and 4 week break, participants who are assigned to this arm will receive Nivolumab with concurrent adjuvant temozolomide treatment Receives: Drug: Nivolumab; Drug: Temozolomide |
| Temozolomide | Active comparator | After radiotherapy and 4 week break, participants who are assigned to this arm will receive the standard treatment of adjuvant temozolomide treatment Receives: Drug: Temozolomide |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 24 months post randomisation of first participant
Secondary outcomes (7)
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.
Measured: 6 months post randomisation
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.
Measured: Through study completion, up to 24 months
Health related quality of life of participants (QLQ C-30)
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.
Measured: Through study completion, up to 24 months
Health related quality of life of participants (QLQ-BN20)
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.
Measured: Through study completion, up to 24 months
Health related quality of life of participants (EuroQoL EQ-5D-5L)
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).
Measured: Through study completion, up to 24 months
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.
Measured: Through study completion, up to 24 months
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).
Measured: Through study completion, up to 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Dec 2019
- Study start22 Feb 2018
- Primary completion28 Jun 2024
- Study completion31 Dec 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Glioblastoma MultiformeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- 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.
- Masking
- None (open label)
- Enrolment
- 103 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Sydney
- Sponsor type
- University, hospital or other
- Collaborators
- Cooperative Trials Group for Neuro-Oncology
- Responsible party
- Sponsor
- Investigators
- Mustafa Khasraw, Study chair, Duke University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04195139
- Sponsor's protocol ID
- COGNO 16/01, CTC 0156
- Other IDs
- ACTRN12617000267358
- Acronym
- NUTMEG
- Status last verified
- Dec 2024
- First submitted
- 18 Nov 2019
- Last updated
- 11 Dec 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
de Melo SM, Elias Nunes da Silva ME, Torloni MR, Riera R, De Cicco K, Latorraca CO, Pinto ACPN. Anti-PD-1 and anti-PD-L1 antibodies for glioma. Cochrane Database Syst Rev. 2025 Jan 8;1(1):CD012532. doi: 10.1002/14651858.CD012532.pub2.
PubMed 39777725
Study at a glance
From the registry record, last updated by the sponsor on 11 Dec 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomised Phase II Study of NivolUmab and TeMozolomide vs Temozolomide Alone in Newly Diagnosed Elderly Patients With Glioblastoma (NUTMEG)
- ClinicalTrials.gov ID
- NCT04195139
- Acronym / sponsor ID
- NUTMEG / COGNO 16/01, CTC 0156
- Conditions
- Glioblastoma Multiforme
- Keywords
- GBM, Astrocytoma WHO grade IV, Elderly, Nivolumab, Temozolomide
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 103 participants (actual)
- Lead sponsor
- University of SydneyUniversity, hospital or other
- Collaborators
- Cooperative Trials Group for Neuro-Oncology
- Study start
- 22 Feb 2018 (actual)
- Primary completion
- 28 Jun 2024 (actual)
- Study completion
- 31 Dec 2025 (estimated)
- First posted
- 11 Dec 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- 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.
| Arm | Type | Receives |
|---|---|---|
| Nivolumab and Temozolomide | Experimental | Drug: Nivolumab, Drug: TemozolomideAfter radiotherapy and 4 week break, participants who are assigned to this arm will receive Nivolumab with concurrent adjuvant temozolomide treatment |
| Temozolomide | Active comparator | Drug: TemozolomideAfter radiotherapy and 4 week break, participants who are assigned to this arm will receive the standard treatment of adjuvant temozolomide treatment |
Who may qualify
- Ages
- 65 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Older adult
Key inclusion criteria (9 listed)
- 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)
Key exclusion criteria (8 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NivolumabAlso: OpdivoParticipants 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). | Drug | Nivolumab and Temozolomide |
| TemozolomideAlso: Temodar, Temodal, TemcadParticipants 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. | Drug | Nivolumab and Temozolomide, Temozolomide |
Primary outcome
Overall survival outcomes
Time frame: 24 months post randomisation of first participant
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.
7 secondary outcomes
Progression Free Survival
Time frame: 6 months post randomisation
Number and severity of adverse events
Time frame: Through study completion, up to 24 months
Health related quality of life of participants (QLQ C-30)
Time frame: Through study completion, up to 24 months
Health related quality of life of participants (QLQ-BN20)
Time frame: Through study completion, up to 24 months
Health related quality of life of participants (EuroQoL EQ-5D-5L)
Time frame: Through study completion, up to 24 months
Neurologic function of participants
Time frame: Through study completion, up to 24 months
Correlating modified RANO and immune related RANO in the experimental arm
Time frame: Through study completion, up to 24 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Dec 2024.
- Derived from this study: PubMed 39777725de Melo SM, Elias Nunes da Silva ME, Torloni MR, Riera R, De Cicco K, Latorraca CO, Pinto ACPN. Anti-PD-1 and anti-PD-L1 antibodies for glioma. Cochrane Database Syst Rev. 2025 Jan 8;1(1):CD012532. doi: 10.1002/14651858.CD012532.pub2.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mustafa Khasraw study chair
Duke University
20 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Nivolumab and Temozolomide in people with Glioblastoma Multiforme, run by University of Sydney at 20 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 11 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 20 sites in Australia, United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall survival outcomes (time frame: 24 months post randomisation of first participant). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04195139, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Dec 2024.