Clinical Trials /

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

NCT04195139

Description:

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.

Related Conditions:
  • Conventional Glioblastoma Multiforme
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Nivolumab and Temozolomide Versus Temozolomide Alone in Newly Diagnosed Elderly Patients With GBM
  • Official Title: A Randomised Phase II Study of NivolUmab and TeMozolomide vs Temozolomide Alone in Newly Diagnosed Elderly Patients With Glioblastoma (NUTMEG)

Clinical Trial IDs

  • ORG STUDY ID: COGNO 16/01, CTC 0156
  • SECONDARY ID: ACTRN12617000267358
  • NCT ID: NCT04195139

Conditions

  • Glioblastoma Multiforme

Interventions

DrugSynonymsArms
NivolumabOpdivoNivolumab and Temozolomide
TemozolomideTemodar, Temodal, TemcadNivolumab and Temozolomide

Purpose

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).
    

Trial Arms

NameTypeDescriptionInterventions
Nivolumab and TemozolomideExperimentalAfter radiotherapy and 4 week break, participants who are assigned to this arm will receive Nivolumab with concurrent adjuvant temozolomide treatment
  • Nivolumab
  • Temozolomide
TemozolomideActive ComparatorAfter radiotherapy and 4 week break, participants who are assigned to this arm will receive the standard treatment of adjuvant temozolomide treatment
  • Temozolomide

Eligibility Criteria

        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
             Cockroft-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. A condition other than GBM, requiring systemic treatment with either corticosteroids
             (> 10 mg daily prednisone or equivalent) or other immunosuppressive medications within
             14 days prior to randomisation. Inhaled or topical steroids, and adrenal replacement
             steroid doses > 10 mg daily prednisone or equivalent, are permitted in the absence of
             active autoimmune disease.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:65 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Overall survival outcomes
Time Frame:24 months post randomisation of first participant
Safety Issue:
Description: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.

Secondary Outcome Measures

Measure:Progression Free Survival
Time Frame:6 months post randomisation
Safety Issue:
Description: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.
Measure:Number and severity of adverse events
Time Frame:Through study completion, up to 24 months
Safety Issue:
Description: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.
Measure:Health related quality of life of participants
Time Frame:Through study completion, up to 24 months
Safety Issue:
Description: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.
Measure:Health related quality of life of participants
Time Frame:Through study completion, up to 24 months
Safety Issue:
Description: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.
Measure:Health related quality of life of participants
Time Frame:Through study completion, up to 24 months
Safety Issue:
Description: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).
Measure:Neurologic function of participants
Time Frame:Through study completion, up to 24 months
Safety Issue:
Description: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.
Measure:Correlating modified RANO and immune related RANO in the experimental arm
Time Frame:Through study completion, up to 24 months
Safety Issue:
Description: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).

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:University of Sydney

Trial Keywords

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

Last Updated

December 9, 2019