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

NCT04195139 | Active Not Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: COGNO 16/01, CTC 0156ACTRN12617000267358
• Study Type: interventional
• Target: 103
• Locations: 2 countries
• Sites: 20

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.

Conditions

Glioblastoma Multiforme

Keywords

GBM; Astrocytoma WHO grade IV; Elderly; Nivolumab; Temozolomide

Outcome Measures

Primary Outcomes (1)

• 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.

  24 months post randomisation of first participant

Secondary Outcomes (7)

• Progression Free Survival

  6 months post randomisation

• Number and severity of adverse events

  Through study completion, up to 24 months

• Health related quality of life of participants (QLQ C-30)

  Through study completion, up to 24 months

• Health related quality of life of participants (QLQ-BN20)

  Through study completion, up to 24 months

• Health related quality of life of participants (EuroQoL EQ-5D-5L)

  Through study completion, up to 24 months

Study Arms (2)

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

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

Drug: Temozolomide

Interventions

Nivolumab 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).

Also known as: Opdivo

Nivolumab and Temozolomide

Temozolomide 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.

Also known as: Temodar, Temodal, Temcad

Nivolumab and Temozolomide; Temozolomide

Eligibility Criteria

• Age: 65 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• 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)
• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Sydney: lead
• Cooperative Trials Group for Neuro-Oncology: collaborator

Study Sites (20)

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Campbelltown Hospital

Campbelltown, New South Wales, 2560, Australia

Location

Chris O'Brien Lifehouse

Camperdown, New South Wales, 2050, Australia

Location

Gosford Hospital

Gosford, New South Wales, 2250, Australia

Location

Newcastle Private Hospital

New Lambton Heights, New South Wales, 2305, Australia

Location

Port Macquarie Hospital

Port Macquarie, New South Wales, 2444, Australia

Location

Prince of Wales Hospital

Randwick, New South Wales, 2031, Australia

Location

Royal North Shore Hospital

Saint Leonards, New South Wales, 2065, Australia

Location

Wollongong Hospital

Wollongong, New South Wales, 2500, Australia

Location

Royal Brisbane and Women's Hospital

Herston, Queensland, 4029, Australia

Location

Icon Cancer Centre

South Brisbane, Queensland, 4101, Australia

Location

Princess Alexandra Hospital

Woolloongabba, Queensland, 4102, Australia

Location

Royal Adelaide Hospital

Adelaide, South Australia, 5000, Australia

Location

Flinders Medical Centre

Bedford Park, South Australia, 5042, Australia

Location

Royal Hobart Hospital

Hobart, Tasmania, 7000, Australia

Location

Monash Medical Centre

Clayton, Victoria, 3168, Australia

Location

Austin Hospital

Heidelberg, Victoria, 3084, Australia

Location

Peter MacCallum Cancer Centre

Melbourne, Victoria, 3000, Australia

Location

Epworth Healthcare

Richmond, Victoria, 3121, Australia

Location

Sir Charles Gairdner Hospital

Nedlands, Western Australia, 6009, Australia

Location

Related Publications (1)

• 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.

  PMID: 39777725 DERIVED

MeSH Terms

Conditions

Glioblastoma

Interventions

Nivolumab; Temozolomide

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Mustafa Khasraw

  Duke University

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: November 18, 2019
• First Posted: December 11, 2019
• Study Start: February 22, 2018
• Primary Completion: June 28, 2024
• Study Completion: December 31, 2025
• Last Updated: December 11, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

AU (19); US (1)