Olaparib and Temozolomide in Treating Patients With Relapsed Glioblastoma

NCT01390571 | Completed Phase 1

• 3 other identifiers: CDR0000702605CRUK-CR0901-11EUDRACT-2010-018615-15
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 7

Brief Summary

RATIONALE: Olaparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Olaparib may help temozolomide kill more tumor cells by making tumor cells more sensitive to the drug. PURPOSE: This phase I trial is studying the side effects and best dose of olaparib and temozolomide in treating patients with relapsed glioblastoma.

Conditions

Brain and Central Nervous System Tumors

Keywords

adult glioblastoma; adult giant cell glioblastoma; adult gliosarcoma; recurrent adult brain tumor

Outcome Measures

Primary Outcomes (3)

• Detection of olaparib in tumor tissue using liquid chromatography mass spectrometry (LC-MS) seen in at least 1 out of the 6 patients treated in stage 1 of the study

• Maximum-tolerated dose of olaparib in combination with temozolomide (stage 2)

• Toxicity profile and dose-limiting toxicity as assessed by NCI CTCAE Version 4.02 (stage 2)

Secondary Outcomes (2)

• Measurement of blood-brain barrier (BBB) disruption and permeability biomarkers by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and diffusion-weighted imaging (DWI) (stage 1 and stage 2 MTD expansion cohort)

• Progression-free survival at 6 months post-surgery as assessed by the Response Assessment in Neuro-Oncology Working Group (RANO) criteria from conventional MRI and clinical assessment (stage 2)

Other Outcomes (11)

• Gene copy number analysis of DNA repair genes

• Quantification of DNA repair gene expression

• Measurement of methylation of the MGMT promoter gene by bisulfite modification of DNA and pyrosequencing

Interventions

olaparib DRUG

temozolomide DRUG

gene expression analysis GENETIC

protein expression analysis GENETIC

laboratory biomarker analysis OTHER

pharmacological study OTHER

diffusion-weighted magnetic resonance imaging PROCEDURE

dynamic contrast-enhanced magnetic resonance imaging PROCEDURE

therapeutic conventional surgery PROCEDURE

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may not qualify if:

• See Disease Characteristics
• No ongoing toxic manifestations from previous treatments except for alopecia or grade 1 toxicities which, in the opinion of the Investigator and the Drug Development Office (DDO), should not exclude the patient
• At least 12 weeks since prior radiotherapy, endocrine therapy, or immunotherapy
• At least 6 weeks since prior major surgery
• At least 4 weeks since prior chemotherapy
• At least 4 weeks since prior immunizations with live vaccines (or expected to receive vaccines during the trial and up to at least 6 months after receiving last study treatment), including BCG and yellow fever vaccines
• No prior PARP inhibitors, including olaparib
• No prior major thoracic or abdominal surgery from which the patient has not yet recovered
• No prior heart surgery
• No pacemakers
• No change to systemic steroids dose within 5 days prior to enrollment (i.e., must be on a stable dose at time of enrollment and remain on a stable dose throughout the treatment period)
• No herbal supplements and/or ingestion of foods known to modulate CYP3A4 enzyme activity from time entered on screening period until 28 days after the last dose of study medication
• No concurrent drugs known to be potent inducers of CYP3A4, including phenytoin, carbamazepine, phenobarbital, rifampicin, rifapentine, rifabutin, nevirapine, modafinil, or St. John wort (wash-out period for phenobarbital is 5 weeks, 3 weeks for all others)
• No concurrent drugs known to be potent inhibitors of CYP3A4, including ketoconazole, itraconazole, ritonavir, indinavir, saquinavir, telithromycin, clarithromycin, or nelfinavir (wash-out period is 1 week)
• No concurrent or planned participation in another interventional clinical study

Sponsors & Collaborators

• Cancer Research UK: lead

Study Sites (7)

Bristol Haematology and Oncology Centre

Bristol, England, BS2 8ED, United Kingdom

Location

Addenbrooke's Hospital

Cambridge, England, CB2 0QQ, United Kingdom

Location

Christie Hospital

Manchester, England, United Kingdom

Location

Royal Marsden Hospital

Sutton, England, United Kingdom

Location

Beatson West of Scotland Cancer Centre

Glasgow, Scotland, United Kingdom

Location

Queen Elizabeth Hospital

Birmingham, B15 2TH, United Kingdom

Location

Western General Hospital

Edinburgh, EH4 2XU, United Kingdom

Location

MeSH Terms

Conditions

Central Nervous System Neoplasms; Glioblastoma; Gliosarcoma; Brain Neoplasms

Interventions

olaparib; Temozolomide; Gene Expression Profiling

Condition Hierarchy (Ancestors)

Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Nervous System Diseases; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Brain Diseases; Central Nervous System Diseases

Intervention Hierarchy (Ancestors)

Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Genetic Techniques; Investigative Techniques

Study Officials

• Anthony Chalmers, Prof

  Beatson West of Scotland Cancer Centre

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Masking: NONE
• Purpose: TREATMENT
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 7, 2011
• First Posted: July 11, 2011
• Study Start: July 1, 2011
• Primary Completion: June 20, 2017
• Study Completion: June 20, 2017
• Last Updated: February 5, 2018

Record last verified: 2018-02

Locations

GB (7)