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

Phase 2Active Not RecruitingNCT04195139

University of Sydney103 enrolled

Overview

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.

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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

103

Conditions

Glioblastoma Multiforme

Eligibility

Sex: ALLMin age: 65 Years

Medical Language ↔ Plain English

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.

Locations (20)

Duke University Medical Center

Durham, North Carolina, United States

Campbelltown Hospital

Campbelltown, New South Wales, Australia

Chris O'Brien Lifehouse

Camperdown, New South Wales, Australia

Gosford Hospital

Gosford, New South Wales, Australia

Newcastle Private Hospital

New Lambton Heights, New South Wales, Australia

Port Macquarie Hospital

Port Macquarie, New South Wales, Australia

Prince of Wales Hospital

Randwick, New South Wales, Australia

Royal North Shore Hospital

Saint Leonards, New South Wales, Australia

Wollongong Hospital

Wollongong, New South Wales, Australia

Royal Brisbane and Women's Hospital

Herston, Queensland, Australia

...and 10 more locations

Outcomes

Primary Outcomes

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.

Time frame: 24 months post randomisation of first participant

Secondary Outcomes

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.

Time frame: 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.