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

NCT ID: NCT04195139

Last Updated: 2024-12-11

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE2

Total Enrollment

103 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-02-22

Study Completion Date

2025-12-31

Brief Summary

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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

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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

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Glioblastoma Multiforme

Keywords

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GBM Astrocytoma WHO grade IV Elderly Nivolumab Temozolomide

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

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 Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Nivolumab and Temozolomide

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

Group Type EXPERIMENTAL

Nivolumab

Intervention Type DRUG

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).

Temozolomide

Intervention Type DRUG

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.

Temozolomide

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

Group Type ACTIVE_COMPARATOR

Temozolomide

Intervention Type DRUG

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.

Interventions

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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).

Intervention Type DRUG

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 Type DRUG

Other Intervention Names

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Opdivo Temodar Temodal Temcad

Eligibility Criteria

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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.
Minimum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Cooperative Trials Group for Neuro-Oncology

UNKNOWN

Sponsor Role collaborator

University of Sydney

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Mustafa Khasraw

Role: STUDY_CHAIR

Duke University

Locations

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Duke University Medical Center

Durham, North Carolina, United States

Site Status

Campbelltown Hospital

Campbelltown, New South Wales, Australia

Site Status

Chris O'Brien Lifehouse

Camperdown, New South Wales, Australia

Site Status

Gosford Hospital

Gosford, New South Wales, Australia

Site Status

Newcastle Private Hospital

New Lambton Heights, New South Wales, Australia

Site Status

Port Macquarie Hospital

Port Macquarie, New South Wales, Australia

Site Status

Prince of Wales Hospital

Randwick, New South Wales, Australia

Site Status

Royal North Shore Hospital

Saint Leonards, New South Wales, Australia

Site Status

Wollongong Hospital

Wollongong, New South Wales, Australia

Site Status

Royal Brisbane and Women's Hospital

Herston, Queensland, Australia

Site Status

Icon Cancer Centre

South Brisbane, Queensland, Australia

Site Status

Princess Alexandra Hospital

Woolloongabba, Queensland, Australia

Site Status

Royal Adelaide Hospital

Adelaide, South Australia, Australia

Site Status

Flinders Medical Centre

Bedford Park, South Australia, Australia

Site Status

Royal Hobart Hospital

Hobart, Tasmania, Australia

Site Status

Monash Medical Centre

Clayton, Victoria, Australia

Site Status

Austin Hospital

Heidelberg, Victoria, Australia

Site Status

Peter MacCallum Cancer Centre

Melbourne, Victoria, Australia

Site Status

Epworth Healthcare

Richmond, Victoria, Australia

Site Status

Sir Charles Gairdner Hospital

Nedlands, Western Australia, Australia

Site Status

Countries

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United States Australia

References

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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.

Reference Type DERIVED
PMID: 39777725 (View on PubMed)

Other Identifiers

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ACTRN12617000267358

Identifier Type: REGISTRY

Identifier Source: secondary_id

COGNO 16/01, CTC 0156

Identifier Type: -

Identifier Source: org_study_id