None listed
Conditions
Brief summary
This study aims to evaluate the safety and effectiveness of a combination of veliparib with radiotherapy, followed by a combination of veliparib with temozolomide (a chemotherapy), to treat patients with newly diagnosed glioblastoma multiforme (a type of brain tumour). Who is it for? You can join this study if you are a person who is recently diagnosed with glioblastoma multiforme (brain tumour), underwent surgery (or have been scheduled to undergo surgery) for this diagnosis and are considered for further treatment with radiotherapy plus temozolomide treatment. Study details: If you like to join this study you will first be screened by your specialist to see if you meet the eligibility criteria to participate in this study. If you are deemed eligible to participate you will be randomly (by chance) assigned to one of two possible treatment groups: Group 1 will receive veliparib together with radiotherapy for 6-7 weeks, followed by a 4 week treatment break, which is again followed by a 6 month treatment with a combination of temozolomide and veliparib. Group 2 will receive receive temozolomide together with radiotherapy for 6-7 weeks, followed by a 4 week treatment break, which is again followed by a 6 month treatment with temozolomide. Your chance to receive the group 1 treatment is twice as high as to receive the group 2 treatment. Participants will be asked to attend clinic visits every 2-4 weeks during the treatment period and then two times more (1 month and 3 months after having received the last treatment). During these visits the specialist will assess the status of your glioblastoma and your physical and mental health, and ask you about your well-being. Participants will also be asked to undergo tests and procedures, such as blood testing, urine testing, scans, and questionnaire completion and to give tissue samples for laboratory research.
Interventions
Eligible participants will be randomised to the study in 2:1 ratio to either Experimental group or Standard group.
The experimental group will receive veliparib capsules 200mg per oral two times per day for 6 weeks with concurrent radiotherapy (60Gy/30 fractions) followed 4 weeks later by a 6 month course of adjuvant temozolomide capsules (150-200mg/m2* per oral days 1-5, every 28 days) given concurrently with veliparib capsules (40mg per oral two times per day).
The standard treatment group w
Eligible participants will be randomised to the study in 2:1 ratio to either Experimental group or Standard group. The experimental group will receive veliparib capsules 200mg per oral two times per day for 6 weeks with concurrent radiotherapy (60Gy/30 fractions) followed 4 weeks later by a 6 month course of adjuvant temozolomide capsules (150-200mg/m2* per oral days 1-5, every 28 days) given concurrently with veliparib capsules (40mg per oral two times per day). The standard treatment group will receive radiotherapy (60Gy/30 fractions) for 6 weeks plus concurrent temozolomide capsules daily per oral (75mg/m2) followed 4 weeks later by a 6 month course of adjuvant temozolomide capsules per oral (150-200mg/m2*) days 1-5 every 28 days * During the adjuvant treatment phase all patients will start to receive temozolomide capsules at dose level 150mg/m2 per oral once daily days 1-5 in the first cycle of therapy. If this dose level is well tolerated, then the dose of temozolomide should be increased in subsequent cycles to 200 mg/m2. If the dose is not escalated in cycle 2, then the dose of temozolomide should remain at 150 mg/m2 for all 6 cycles. To ensure appropriate control on the distribution of experimental treatment the Pharmacy Department at participating institutions will maintain a record of veliparib study drug received from the sponsor, the amounts dispensed for each patient, the amounts of study drug returned and the amounts destructed. Patients assigned to the veliparib study drug arm will be asked to return unused and empty study drug containers at each return visit to assess compliance to the treatment. Temozolomide is part of standard of care and drug dispensing and compliance will be monitored according to local hospital practices. The radiotherapy treatment is standard of care and consists of a conventionally fractionated regimen, delivering a total dose of 60Gy, in a once daily schedule of 2 Gy per fraction for a total of 30 fractions, completed optimally in 6 weeks but up to a maximum of 7 weeks.
Sponsors
The University of Sydney
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1) Adults, aged 18 years or older, newly diagnosed histologically confirmed GBM (WHO grade IV glioma) following surgery, with unmethylated MGMT promoter gene whom are considered suitable for radiotherapy (RT) plus concurrent temozolomide (TMZ), followed by adjuvant temozolomide (TMZ) NOTE - Patients who undergo biopsy only are eligible only if standard RT and TMZ treatment is considered appropriate; 2) Available tissue for MGMT and biomarker analysis; 3) ECOG 0-2 if 70 years or younger, or ECOG 0 if older than 70 years; 4) Life expectancy of more than 12 weeks; 5) Adequate bone marrow function (platelets greater than 100 x 109/L, ANC greater than 1.5 x 109/L); 6) Adequate liver function (ALT/AST less than 1.5 x ULN); 7) Adequate renal function (creatinine clearance greater than 50 ml/min measured using Cockroft-Gault see appendix 16.4); 8) Willing and able to comply with all study requirements, including treatment, timing and/or nature of required assessments; 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) No prior chemotherapy or recent cranial radiation within the last 2 years. No other prior or concomitant therapies for GBM allowed, excepting surgery NOTE - Patients who had previous grade I-III glioma and have progressed to GBM are eligible assuming that they have not received prior cranial radiotherapy or TMZ for the treatment of glioma; 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. NOTE - Patients with localised cancer free of metastatic disease and of very low risk of recurrence are eligible. Eligibility of patients with localised cancer must be confirmed by the Study Chair. 5) Significant infection, including chronic active hepatitis B, hepatitis C, or HIV. Testing for these is not mandatory unless clinically indicated; 6) Concurrent illness, including severe infection that may jeopardise the ability of the patient to undergo the procedures outlined in this protocol with reasonable safety; 7) Serious medical or psychiatric conditions that might limit the ability of the patient to comply with the protocol; 8) 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; 9) Patients with a duration of more than 7 weeks from surgery to the start of RT.
Outcome results
None listed