Phase 1 trial of olaparib with temozolomide in relapsed glioblastoma

Phase 1

Completed

• Conditions: Brain Tumour; Cancer; Malignant neoplasm of brain

• Registration Number: ISRCTN47380065
• Lead Sponsor: Cancer Research UK

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2011-08-10
• Study Completion: 2017-01-02
• Last Update Posted: 13 May 2019

Recruitment & Eligibility

• Status: Completed
• Sex: All
• Target Recruitment: 45

Inclusion Criteria

1. Histological proven glioblastoma (World Health Organisation[WHO] Grade 4).
2. Radiological diagnosis of recurrent or progressive disease according to RANO criteria, which is suitable for palliative resection.
3. Patients should have enough resectable tumour tissue for sampling requirements in the opinion of the neurosurgeon.
4. Prior 1st line treatment with radical radiotherapy, or chemoradiation followed by adjuvant chemotherapy (no prior
chemotherapy for recurrent disease is allowed).
5. Aged between 18 and 70 years.
6. Life expectancy > 12 weeks
7. WHO performance status of 02
8. Haematological and biochemical indices within the ranges shown below. These measurements must be performed within one week before the patient goes on study.
Haemoglobin (Hb) = 9.0 g/dL
Absolute neutrophil count (ANC) = 1.5 x 109/L
Platelet count = 100 x 109/L
Serum bilirubin = 1.5 x upper limit of normal (ULN)
ALT or AST = 2.5 x ULN
Either: Calculated creatinine clearance = 50 mL/min Or: Isotope clearance measurement = 50 mL/min (uncorrected)
9. Ability to swallow and retain oral medications.
10. Written (signed and dated) informed consent and be capable of cooperatingwith treatment, scans and followup

Exclusion Criteria

1. Radiotherapy, endocrine therapy or immunotherapy during the previous 12 weeks before treatment, or chemotherapy during the 4 weeks before treatment.
2. Any previous treatment with a PARP inhibitor, including olaparib.
3. Ongoing toxic manifestations of previous treatments. Exceptions to this are alopecia or Grade 1 toxicities, which in the opinion of the Investigator and the Drug Development Office (DDO) should not exclude the patient.
4. Change to systemic steroids dose within the five days prior to enrolment (ie. must be on a stable dose at time of
enrolment).
5. Ability 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 (oral, injected or implanted hormonal contraception and condom, have a intrauterine
device and condom, diaphragm with spermicidal gel and condom) for four weeks before entering the trial, during the trial and for six months afterwards are
considered eligible.
6. Male patients with partners of childbearing potential (unless they agree to take measures not to father children by using one form of highly effective contraception [condom plus spermicide] during the trial and for six months afterwards). Men with pregnant or lactating partners should be advised to use barrier method contraception (for example, condom plus spermicidal gel) to prevent exposure to the foetus or neonate.
7. Major thoracic or abdominal surgery from which the patient has not yet recovered.
8. At high medical risk because of nonmalignant systemic disease including active uncontrolled infection.
9. Known to be serologically positive for hepatitis B, hepatitis C or human immunodeficiency virus (HIV).
10. Concurrent congestive heart failure, prior history of class III/ IV cardiac disease (New York Heart Association [NYHA]
refer to Appendix 3), prior history of cardiac ischaemia or prior history of cardiac arrhythmia within the previous 12 months.
11. Patients with pacemakers, a history of previous heart surgery, any major surgery in the preceding six weeks, metal fragments in their eyes, shrapnel or bullet injuries are excluded (on the basis of their unsuitability to undergo MRI scans). Patients with metal implants or tattoos should be discussed with MRI staff.
12. Grand mal seizures occurring = 3 times per week over the past month.
13. Patients with gastrointestinal disorders likely to interfere with absorption of the study medication.
14. Patients taking drugs known to be potent inhibitors or inducers of CYP3A4 including phenytoin, carbamazepine and phenobarbitone which cannot be stopped for the duration of the trial.
15. Immunisations with live vaccines received within the previous four weeks (or expected to receive during the trial and up to at least six months after receiving last study treatment). Including BCG and yellow fever.
16. Known hypersensitivity to any of the components of olaparib.
17. Known hypersensitivity to temozolomide (TMZ), or to any of its components, or to dacarbazine (DTIC) (Stage 2 only).
18. Known lactose intoleran

Study & Design

• Study Type: Interventional
• Study Design: Not specified