Brain and Central Nervous System TumorsPhase 1NCT01390571
Olaparib and Temozolomide in Treating Patients With Relapsed Glioblastoma
A Phase 1 study testing olaparib, temozolomide and gene expression analysis in people with Brain and Central Nervous System Tumors, run by Cancer Research UK at 7 sites in United Kingdom.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Brain and Central Nervous System Tumors
- What is being tested?
- olaparib, temozolomide and gene expression analysis
- Type of treatment
- Surgery or procedure
- How many people
- 34 participants
- Where
- 7 sitesUnited Kingdom
- Study dates
- Jul 2011to 20 Jun 2017
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
None listed.
Who cannot join
- 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
Show all 19Show fewer
- 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
- Participation in an observational study is acceptable
- No concurrent warfarin (patients requiring anticoagulation should be given subcutaneous low molecular weight heparin)
- No other concurrent anticancer therapy (including radiotherapy) or investigational drugs
- No blood transfusions within 4 weeks prior to study start of features suggestive of myelodysplasia or AML
Trial locations and contacts
7 sites in 1 country.
7 sites in 1 country
United Kingdom7 sites
Queen Elizabeth Hospital
Birmingham, B15 2TH
Bristol Haematology and Oncology Centre
Bristol, England, BS2 8ED
Addenbrooke's Hospital
Cambridge, England, CB2 0QQ
Western General Hospital
Edinburgh, EH4 2XU
Beatson West of Scotland Cancer Centre
Glasgow, Scotland
Christie Hospital
Manchester, England
Royal Marsden Hospital
Sutton, England
About this study
Official 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
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.
Read the detailed description
OBJECTIVES:
Primary
- To determine whether olaparib crosses the blood-brain barrier (BBB) and achieves tumor penetration in patients with relapsed glioblastoma. (Stage 1)
- To determine the safety and tolerability of the combination of olaparib and temozolomide in patients with relapsed glioblastoma. (Stage 2)
Secondary
- To assess BBB disruption and BBB permeability in patients with relapsed glioblastoma. (Stage 1 and stage 2 maximum-tolerated dose [MTD] expansion cohort)
- To assess the possible anti-tumor activity of the combination of olaparib and temozolomide in patients with relapsed glioblastoma. (Stage 2)
Tertiary
- To assess biological markers as possible predictors of olaparib efficacy in patients with glioblastoma.
- To optimize techniques for measuring DNA damage responses to PARP inhibition in tumor tissue.
- To determine plasma concentration of olaparib at the time of surgery in patients with glioblastoma.
- To evaluate the PARP inhibition at the time of surgery in peripheral blood mononuclear cells (PBMCs).
OUTLINE: This is a multicenter, dose-escalation study.
- Stage 1: Patients receive fixed-dose oral olaparib twice daily for 3 days prior to resection and then receive a dose of oral olaparib on the morning of the resection. After the surgical resection, patient receive standard of care treatment. Patients undergo dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and diffusion-weighted imaging (DWI) scans to assess the disruption and permeability of the blood-brain barrier (BBB).
Stage 1 is complete and it was proven that olaparib can cross the BBB and achieve tumour penetration in glioblastoma patients.
- Stage 2: Patients receive escalating doses of oral olaparib once or twice daily for 3 days prior to resection and then receive a dose of oral olaparib on the morning of the resection. After recovery from surgery, patients receive oral olaparib once or twice daily and oral temozolomide once daily on days 1-42. Treatment repeats every 8 weeks for up to 3 courses in the absence of disease progression or unacceptable toxicity. Patients may receive 3 additional courses of treatment in the absence of disease progression.
Once the maximum tolerated dose (MTD) is established, 10 more patients are treated at the MTD as stage 2 MTD expansion cohort. These patients also undergo DCE-MRI and DWI scans.
All patients undergo blood collection periodically for pharmacokinetic and pharmacodynamic studies.
After completion of study treatment, patients are followed up for 28 days and then monthly until resolution of study drug-related adverse events.
Peer Reviewed and Funded or Endorsed by Cancer Research UK.
- Conditions
- Brain and Central Nervous System Tumors
- Being tested
- olaparib, temozolomide, gene expression analysis, protein expression analysis, laboratory biomarker analysis
- Keywords
- adult glioblastoma, adult giant cell glioblastoma, adult gliosarcoma, recurrent adult brain tumor
- Medical subject headings
- Central Nervous System Neoplasms, Glioblastoma, Gliosarcoma, Brain Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
olaparibDrug
temozolomideDrug
gene expression analysisGenetic
protein expression analysisGenetic
laboratory biomarker analysisOther
diffusion-weighted magnetic resonance imagingProcedure or surgery
dynamic contrast-enhanced magnetic resonance imagingProcedure or surgery
therapeutic conventional surgeryProcedure or surgery
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jul 2011 (estimated)
- Study startJul 2011
- Primary completion20 Jun 2017
- Study completion20 Jun 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Brain and Central Nervous System TumorsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Masking
- None (open label)
- Enrolment
- 34 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Cancer Research UK
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Anthony Chalmers, Prof, Principal investigator, Beatson West of Scotland Cancer Centre
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01390571
- Sponsor's protocol ID
- CDR0000702605
- Other IDs
- CRUK-CR0901-11, EUDRACT-2010-018615-15
- Status last verified
- Feb 2018
- First submitted
- 7 Jul 2011
- Last updated
- 5 Feb 2018
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Feb 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official 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
- ClinicalTrials.gov ID
- NCT01390571
- Acronym / sponsor ID
- CDR0000702605
- Conditions
- Brain and Central Nervous System Tumors
- Keywords
- adult glioblastoma, adult giant cell glioblastoma, adult gliosarcoma, recurrent adult brain tumor
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 34 participants (estimated)
- Lead sponsor
- Cancer Research UKUniversity, hospital or other
- Study start
- Jul 2011
- Primary completion
- 20 Jun 2017 (actual)
- Study completion
- 20 Jun 2017 (actual)
- First posted
- 11 Jul 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
OBJECTIVES:
Primary
- To determine whether olaparib crosses the blood-brain barrier (BBB) and achieves tumor penetration in patients with relapsed glioblastoma. (Stage 1)
- To determine the safety and tolerability of the combination of olaparib and temozolomide in patients with relapsed glioblastoma. (Stage 2)
Secondary
- To assess BBB disruption and BBB permeability in patients with relapsed glioblastoma. (Stage 1 and stage 2 maximum-tolerated dose [MTD] expansion cohort)
- To assess the possible anti-tumor activity of the combination of olaparib and temozolomide in patients with relapsed glioblastoma. (Stage 2)
Tertiary
- To assess biological markers as possible predictors of olaparib efficacy in patients with glioblastoma.
- To optimize techniques for measuring DNA damage responses to PARP inhibition in tumor tissue.
- To determine plasma concentration of olaparib at the time of surgery in patients with glioblastoma.
- To evaluate the PARP inhibition at the time of surgery in peripheral blood mononuclear cells (PBMCs).
OUTLINE: This is a multicenter, dose-escalation study.
- Stage 1: Patients receive fixed-dose oral olaparib twice daily for 3 days prior to resection and then receive a dose of oral olaparib on the morning of the resection. After the surgical resection, patient receive standard of care treatment. Patients undergo dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and diffusion-weighted imaging (DWI) scans to assess the disruption and permeability of the blood-brain barrier (BBB).
Stage 1 is complete and it was proven that olaparib can cross the BBB and achieve tumour penetration in glioblastoma patients.
- Stage 2: Patients receive escalating doses of oral olaparib once or twice daily for 3 days prior to resection and then receive a dose of oral olaparib on the morning of the resection. After recovery from surgery, patients receive oral olaparib once or twice daily and oral temozolomide once daily on days 1-42. Treatment repeats every 8 weeks for up to 3 courses in the absence of disease progression or unacceptable toxicity. Patients may receive 3 additional courses of treatment in the absence of disease progression.
Once the maximum tolerated dose (MTD) is established, 10 more patients are treated at the MTD as stage 2 MTD expansion cohort. These patients also undergo DCE-MRI and DWI scans.
All patients undergo blood collection periodically for pharmacokinetic and pharmacodynamic studies.
After completion of study treatment, patients are followed up for 28 days and then monthly until resolution of study drug-related adverse events.
Peer Reviewed and Funded or Endorsed by Cancer Research UK.
Study design
- Primary purpose
- Treatment
- Masking
- None (open label)
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (0 listed)
Key exclusion criteria (19 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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 or surgery | – |
| dynamic contrast-enhanced magnetic resonance imaging | Procedure or surgery | – |
| therapeutic conventional surgery | Procedure or surgery | – |
Primary outcome
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)
2 secondary outcomes
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)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Feb 2018.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Anthony Chalmers, Prof principal investigator
Beatson West of Scotland Cancer Centre
7 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing olaparib, temozolomide and gene expression analysis in people with Brain and Central Nervous System Tumors, run by Cancer Research UK at 7 sites in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 0 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 Feb 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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. The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Feb 2018.