Phase 1 trial of olaparib with temozolomide in relapsed glioblastoma

• Research type

  Research Study

• Full title

  A Cancer Research UK Phase I trial of olaparib (AZD2281), an oral PARP Inhibitor, in combination with extended low-dose oral temozolomide in patients with relapsed glioblastoma

• IRAS ID

  67696

• Contact name

  Anthony Chalmers - Miss Jane Peters

• Sponsor organisation

  cancer.org.uk

• Eudract number

  2010-018615-15

• Research summary

  We wish to find out if a combination of Temozolomide and a PARP (Poly (ADP-ribose) polymerase) inhibitor called Olaparib will be useful in treating patients with the most aggressive type of brain cancer called glioblastoma. The purpose of this Phase I study is to see if Olaparib crosses the blood brain barrier (BBB) and achieves tumour penetration in recurrent glioblastoma, and to establish its safety and toxicity profile in combination with extended low-dose Temozolomide therapy.This trial will be the first time Olaparib will be given to glioblastoma patients. To be eligible for the study, patients must have previously received radical radiotherapy, with or without concomitant temozolomide, but must not have received any chemotherapy treatment for recurrent disease. There are 2 stages of this trial:In stage 1 six patients will receive Olaparib tablets at a dose level of 200mg twice daily for three days before brain surgery. A dose of Olaparib will also be given on the morning of brain surgery. These patients will not be considered for Stage 2.In stage 2, 16-28 patients will receive increasing dose levels of Olaparib (up to 200mg twice daily) in combination with daily, low dose Temozolomide. This combination has not been given before to humans. Patients will receive Olaparib tablets for three days prior to surgery of the glioblastoma. They will also receive a dose of Olaparib on the morning of the surgery. When patients have recovered from surgery they will start the Olaparib/Temozolomide combination therapy. One cycle will consist of 42 days treatment followed by a 14 day rest period. Combination therapy will then be repeated using this schedule for up to three cycles until there is disease progression or unacceptable toxicity. If the patient has not progressed after three cycles, they may be treated for a further three cycles following approval from sponsor. The study will be conducted at 4 NHS hospitals and standard safety assessments will be performed throughout the trial.

• REC name

  Scotland A REC

• REC reference

  11/AL/0213

• Date of REC Opinion

  17 May 2011

• REC opinion

  Further Information Favourable Opinion