CompletedPhase 3ACTRN12620000048987

The Multi-Arm GlioblastoMa Australasia (MAGMA) Trial is a platform trial that will assess a number of options in standard of care for the management of glioblastoma. Initial questions of interest are: QUESTION 1 whether or not to give a cycle of temozolomide prior to chemoradiotherapy and QUESTION 2: whether to give 6 cycles of temozolomide after chemoradiotherapy, or continue monthly treatment until disease progression

A multi-arm multi-stage, multi-centre, phase III (MAMS) platform trial that aims to assess hypotheses against a common standard-of-care control arm for the management of people with glioblastoma. Initial questions of interest are: QUESTION 1: whether to give metronomic temozolomide as soon as possible following surgery prior to chemoradiotherapy; and QUESTION 2: whether to give a plan for 6 cycles of standard schedule adjuvant temozolomide chemotherapy (5/28 day cycles) after chemoradiotherapy, or continue temozolomide until progression.

Sponsor

NHMRC Clinical Trials Centre (CTC), University of Sydney

Enrollment

300 participants

Start Date

Sep 15, 2020

Study Type

Interventional

Conditions

Glioblastoma

Summary

This study aims to evaluate the use of temozolomide in different regimes for Glioblastoma. The trial is testing two changes to the usual schedule of treatment. Who is it for? You may eligible for this study if you are a male or female aged 18 years or older, with newly diagnosed, histologically confirmed grade IV malignant glioblastoma. For the initial questions of interest, participants will be randomly allocated (50/50) chance to one of two treatment groups, to either QUESTION 1: Intervention Arm 1: After surgery, start temozolomide as soon as possible prior to chemoradiotherapy Control Arm 2: After surgery, start temozolomide at the same time as radiotherapy QUESTION 2: Intervention Arm 1: After chemoradiotherapy, take adjuvant temozolomide until disease progression Control Arm 2: After chemoradiotherapy, take adjuvant temozolomide for 6 cycles For participants that choose not to be randomly allocated treatment will be at patient/doctor discretion. All participants will be asked to have blood tests and scans as you would for usual treatment, the extra things requested are to fill out questionnaires and donate extra blood tests. It is hoped this research will help identify if starting temozolomide earlier than usual and/or continuing treatment with temozolomide for longer than usual will improve the outcomes of people with glioblastoma and assist development of future treatments.

Eligibility

Sex: Both males and femalesMin Age: 18 Yearss

Inclusion Criteria9

Adults, aged 18 years and older, with newly diagnosed histologically confirmed grade IV malignant glioblastoma (any IDH mutation status) or glioma with molecular features of GBM (e.g. IDH-wildtype grade III high grade glioma, which have been confirmed to have the same prognosis as glioblastoma (grade IV) patients, and are now functionally treated as GBM39)
Adequate recovery from surgical resection
ECOG performance status of 0-2
Previous surgery for a low-grade glioma is allowed, if there was no radiation or chemotherapy administered at that time
Adequate bone marrow function (platelets greater than or equal to 100 x 109/L, ANC greater than or equal to 1.5 x 109/L)
Adequate liver function (ALT/AST less than 3 x ULN)
Adequate renal function (creatinine clearance greater than 30ml/min)
Willing and able to comply with all study requirements, including treatment, timing and nature of required assessments
Signed, written informed consent

Exclusion Criteria10

Recurrence of glioblastoma
Comorbidities considered to provide a safety concern for use of TMZ, e.g. idiopathic
autoimmune thrombocytopenia or other haematological diease causing cytopaenias
Other contraindications to TMZ
Cranial irradiation within 2 years prior to registration
Other co-morbidities or conditions that may compromise assessment of key outcomes
History of another malignancy within 2 years prior to registration. Patients with adequately treated carcinoma-in-situ of the prostate, breast or cervix, melanoma-in-situ, basal cell carcinoma of the skin, squamous cell carcinoma of the skin, non-muscle invasive transitional cell carcinoma of the bladder or low grade prostate cancer not requiring treatment (ISUP 1; Gleason grade less than or equal to 6) may be included in this study.
Concurrent illness, including severe or chronic bacterial or viral infection that may jeopardise the ability of the patient to undergo the procedures outlined in this protocol with reasonable safety. Patients with adequately treated hepatitis B, hepatitis C or human immunodeficiency virus at low risk of acquired immunodeficiency syndrome-related outcomes may be included in this study.
Presence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule, including alcohol dependence or drug abuse
Pregnancy, lactation, or inadequate contraception. Women must be post-menopausal, infertile, or use a reliable means of contraception. Women of childbearing potential must have a negative pregnancy test done within 7 days prior to registration. Men must have been surgically sterilised or use a (double if required) barrier method of contraception.

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Interventions

For each treatment question, patients will be randomised to a specific arm, unless they specifically choose not to participate in that randomisation, in which case treatment will be at patient/doctor

For each treatment question, patients will be randomised to a specific arm, unless they specifically choose not to participate in that randomisation, in which case treatment will be at patient/doctor discretion. Temozolomide is administered orally and daily at below described doses for patients allocated to Arm 1 (intervention) of each question. Compliance will be determined at each clinic visit by obtaining the patient history and estimating the level of compliance. QUESTION 1 whether to give temozolomide as soon as possible following surgery prior to chemoradiotherapy or start at same time when radiotherapy begins. Intervention Arm 1 - After surgery, start temozolomide as soon as possible prior to chemoradiotherapy. Initial treatment will be at 75mg/m2 per day and will continue through radiotherapy. QUESTION 2 whether to give 6 cycles of adjuvant temozolomide after chemoradiotherapy or continue adjuvant temozolomide until disease progression. Intervention Arm 1 - After chemoradiotherapy, take adjuvant temozolomide until disease progression. Treatment will commence approximately 4 weeks following chemoradiotherapy. Cycle 1 will be given at 150mg/m2 and subsequent cycles at 200mg/m2 for days 1-5 of a 28 day cycle. Participation in both or either questions will determined by patient eligibility and at the patient/doctor discretion.