Short-course radiotherapy plus olaparib for patients with a primary brain tumour and not suitable for radical chemo-radiation.
- Conditions
- glioblastomaTherapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2014-001216-19-GB
- Lead Sponsor
- HS Greater Glasgow & Clyde
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 194
1. Age =70: WHO performance status 0 or 1 at initial oncology consultation
2. Phase I only: Age 18 – 69: WHO performance status 2 at initial oncology consultation or performance status 0-1 but otherwise unsuitable for radical radiotherapy with concomitant and adjuvant temozolomide
3. Phase II and dose escalation substudy only:Age 65- 69; WHO performance status 0, 1 or 2 at initial oncology consultation and unsuitable for radical radiotherapy with concomitant and adjuvant temozolomide
4. Phase II and dose escalation substudy only: Age 18- 64; WHO performance status 2 at initial oncology consultation or performance status 0-1 but otherwise unsuitable for radical radiotherapy with concomitant and adjuvant temozolomide
5. Histologically confirmed diagnosis of glioblastoma
6. Phase II and dose escalation substudy only; Sufficient tumour material for MGMT promoter methylation assay
7. Life expectancy greater than 12 weeks
8. No previous radiotherapy or chemotherapy for primary or secondary CNS malignancy
9. Adequate haematological, hepatic and renal function defined as below:
•Haemoglobin = 100 g/L (no blood transfusions in the 28 days prior to trial entry)
•Absolute neutrophil count = 1.5 x 109/L
•White Blood Cells =3x109/L
•Platelet count = 100 x 109/L
•Bilirubin = 1.5 x upper limit of normal (ULN)
•Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) = 2.5 x ULN
•Adequate renal function with creatinine clearance / glomerular filtration rate > 50 ml/min. If the creatinine clearance / glomerular filtration rate is less than 50 ml/min as calculated by the Cockroft-Gault/Wright formula, then the creatinine clearance / glomerular filtration rate should be measured by either a radio-isotope technique or by 24-hour urine collection as per local practice
10. Ability to provide written informed consent prior to participating in the trial and any trial related procedures being performed
11. Willingness to comply with scheduled visits, treatment plans and laboratory tests and other trial procedures
12. Ability to swallow oral medications
13. Evidence of non-childbearing status for women of childbearing potential: negative urine or serum pregnancy test within 7 days of trial entry
Post-menopausal is defined as:
•Amenorrheic for 1 year or more following cessation of exogenous hormonal treatments
•LH and FSH levels in the post-menopausal range for women under 50
•Or surgical sterilisation (bilateral oophorectomy or hysterectomy)
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 20
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 174
1. WHO performance status >2
2. Life expectancy less than 12 weeks
3. Active concurrent malignancy (except non-melanoma skin cancer or in situ carcinoma of the cervix). If history of prior malignancy, must be disease-free for >5 years
4. Prior treatment for primary or secondary CNS malignancy
5. Confusion or altered mental state that would prohibit understanding and giving of informed consent
6. Concomitant treatment with medicines listed as 'prohibited' or 'excluded' in section 5.10 of protocol
7. Female patients who are able to become pregnant (or already pregnant or lactating). However, those female patients who have a negative serum or urine pregnancy test before enrolment and agree to use two highly effective forms of contraception detailed in section 7.1.12, effective at the first administration of olaparib, throughout the trial, and for at least one month afterwards, are considered eligible
8. Male patients with partners of child-bearing potential (unless they agree to take measures not to father children by using one form of highly effective contraception detailed in section 7.1.12, effective at the first administration of IMP, throughout the trial, and for three months afterwards or 6 months if receiving temozolomide). Men with pregnant or lactating partners should be advised to use barrier method contraception to prevent exposure to the foetus or neonate. Female partners (of childbearing potential) of male patients should also use a highly effective form of contraception as detailed in section 7.1.12
9. Administration of any investigational drug within 28 days prior to receiving the first dose of trial treatment
10. Any previous treatment with a PARP inhibitor, including olaparib
11. Blood transfusions within 28 days prior to trial entry
12. Patients with myelodysplastic syndrome/acute myeloid leukaemia
13. Major surgery within 14 days of starting trial treatment and patients must have recovered from any effects of major surgery
14. Patients with a known hypersensitivity to olaparib or temozolomide or dacarbazine or any of the excipients of the product
15. Patients with uncontrolled seizures
16. Patients who are known to be HIV positive, or who are known to have positive Hepatitis B or C serology
17. Phase II only: Methylation of MGMT promoter region confirmed by central laboratory testing, or an inconclusive MGMT test result
18. Dose escalation substudy only: Unmethylation of MGMT promoter region confirmed by central laboratory testing, or an inconclusive MGMT test result
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method