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Malignant GliomasPhase 1/2OLA-TMZ-RTE-01NCT03212742

Phase I/IIa Study of Concomitant Radiotherapy With Olaparib and Temozolomide in Unresectable High Grade Gliomas Patients

A Phase 1/2 study testing Olaparib, Temozolomide (TMZ) and IMRT (Intensity Modulated Radiation Therapy) in people with Malignant Gliomas and Radiotherapy, run by Centre Francois Baclesse at 15 sites in France.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

Trial summary

The Stupp protocol is the standard treatment of glioblastoma multiform (GBM) which prognosis remains poor. The non-dividing nature of normal brain cells provides an opportunity to enhance the therapeutic ratio by combining radiation with inhibitors of replication-specific DNA repair pathways such poly(ADP-ribose)… Read more about this study

Who is it for?
Ages 18 to 70 years
Conditions the study is for
Malignant Gliomas, Radiotherapy, PARP Inhibitor
What is being tested?
Olaparib, Temozolomide (TMZ) and IMRT (Intensity Modulated Radiation Therapy)
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
91 participants
Where
15 sitesFrance
Study dates
4 Sep 2017to 31 Dec 2026
Phase
Phase 1/2
Are there results?
Not yet: the study is under way

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 to 70 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Provision of signed informed consent prior to any study specific procedures
  • Histologically-confirmed diagnosis of glioblastoma (IDH-wildtype, IDH-mutant or NOS, except gliosarcoma), non resectable or partially resectable with a residual tumor on pre-radiotherapy MRI. The presence of a residual disease will be assessed by the radiologist on the pre-radiotherapy imaging as compared with initial imaging.
  • IMRT must start within 6 weeks after histological diagnosis
  • Age between 18 and 70 years ;
  • Neurologically asymptomatic or pauci-symptomatic patients. Patients with moderated neurological symptoms without systemic corticosteroids treatment or with a stable dose of corticosteroids during the study as long as these were started at least 4 weeks prior to treatment can be included.
  • Adequate bone marrow and organ function measured within 15 days prior to administration of study treatment as defined below:
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  • Haemoglobin ≥ 10.0 g/dL with no blood transfusions (packed red blood cells and platelet transfusions) in the past 28 days before start of treatment
  • Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
  • o No features suggestive of MDS/AML on peripheral blood smear
  • Platelet count ≥ 100 x 109/L
  • White blood cells (WBC) > 3x109/L
  • Total bilirubin ≤ 1.5 x institutional upper limit of normal
  • AST (SGOT)/ALT (SGPT) ≤ 2.5 x institutional upper limit of normal
  • Creatinine clearance estimated using the Cockcroft-Gault equation of ≥51 mL/min:
  • Estimated creatinine clearance = [(140-age(years)) x weight(kg) (x Fsex) ] / [serum creatinine (mg/dL) x 72] where Fsex=0.85 for females and Fsex=1 for males.
  • ECOG performance status 0-2
  • Patients must have a life expectancy ≥ 16 weeks.
  • Women of childbearing potential (WOCBP) and men under efficient contraception during treatment and at least 6 months after the end of treatment.
  • Evidence of non-childbearing status for women of childbearing potential: negative urine or serum pregnancy test within 28 days of study treatment, confirmed prior to treatment on day 1.
  • Postmenopausal (if applicable) 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,
  • radiation-induced oophorectomy with last menses >1 year ago,
  • chemotherapy-induced menopause with >1 year interval since last menses,
  • or surgical sterilisation (bilateral oophorectomy or hysterectomy).
  • Male patients and their partners, who are sexually active and of childbearing potential, must agree to the use of two highly effective forms of contraception in, throughout the period of taking study treatment and for 3 months after last dose of study drug(s) to prevent pregnancy in a partner.
  • Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.
  • Subjects affiliated to an appropriate social security system

Who cannot join

  • Any prior radiotherapy to brain
  • Any prior chemotherapy or immunotherapy
  • Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site)
  • Candidate for a concomitant therapy with Tumor-Treating Fields during the maintenance treatment [70]
  • Previous enrolment in the present study
  • Participation in another clinical trial protocol within 30 days prior to enrolment;
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  • Any previous treatment with a PARP inhibitor, including olaparib.
  • Patients with second primary cancer, except: adequately treated non-melanoma skin cancer, curatively treated in-situ cancer of the cervix, or other solid tumours curatively treated with no evidence of disease for ≥ 5 years
  • Gadolinium hypersensitivity, or any contraindication to undergo MRI examination (Pacemaker, brain aneurysms clips)
  • Patients who had no initial pre-surgery contrast enhanced MRI scan including the standard sequences (T1 non enhanced, T1 contrast enhanced, T2 FLAIR)
  • Patients receiving any systemic chemotherapy, radiotherapy (except for palliative reasons), within 2 weeks from the last dose prior to study treatment. The patient can receive a stable dose of bisphosphonates for bone metastases, before and during the study as long as these were started at least 4 weeks prior to treatment with study drug.
  • Concomitant use of known strong CYP3A inhibitors (eg. itraconazole, telithromycin, clarithromycin, protease inhibitors boosted) or moderate CYP3A inhibitors (eg. ciprofloxacin, erythromycin, diltiazem, fluconazole, verapamil). The required washout period prior to starting olaparib is 2 weeks.
  • Concomitant use of known strong (eg. phenobarbital, phenytoin, rifampicin, rifabutin, rifapentine, carbamazepine, and St John's Wort ) or moderate CYP3A inducers (eg. bosentan, modafinil). The required washout period prior to starting olaparib is 5 weeks for phenobarbital and 3 weeks for other agents.
  • Resting ECG with QTc > 470 msec detected on 2 or more time points within a 24 hour period or family history of long QT syndrome. If ECG demonstrates QTc > 470 msec, patient will be eligible only if repeat ECG demonstrates QTc ≤470 msec;
  • Blood transfusions within 1 month prior to study start
  • Previous allogenic bone marrow transplant or double umbilical cord blood transplantation (dUCBT)
  • Patients with myelodysplastic syndrome/acute myeloid leukaemia or with features suggestive of MDS/AML.
  • Major surgery within 14 days of starting study treatment and patients must have recovered from any effects of any major surgery.
  • Patients considered a poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease or active, uncontrolled infection. Examples include, but are not limited to, uncontrolled ventricular arrhythmia, recent (within 3 months) myocardial infarction, uncontrolled major seizure disorder, unstable spinal cord compression (untreated and unstable for at least 28 days prior to study entry), superior vena cava syndrome, extensive bilateral lung disease on HRCT scan or any psychiatric disorder that prohibits obtaining informed consent.
  • Patients unable to swallow orally administered medication and patients with gastrointestinal disorders likely to interfere with absorption of the study medication (inflammatory bowel disease, major bowel resection …)
  • Pregnant or breast feeding women.
  • Immunocompromised patients, e.g., patients who are known to be serologically positive for human immunodeficiency virus (HIV) and are receiving antiviral therapy.
  • Patients with known active hepatitis (i.e., Hepatitis B or C) due to risk of transmitting the infection through blood or other body fluids.
  • Patients with a known hypersensitivity to olaparib or any of the excipients of the product.
  • For temozolomide treatment, patients with a known galactose intolerance, a Lapp lactase deficit or a glucose or galactose malabsorption syndrome (rare hereditary diseases)
  • Patients with uncontrolled epileptic seizures.
  • Neurological, addictive or psychiatric disorder;
  • Lack of availability for clinical follow-up assessments;
  • Persons protected by a legal regime (guardianship, trusteeship).

Trial locations and contacts

15 sites in 1 country.

15 sites in 1 country

France15 sites

  • CHU

    Amiens

  • Institut de Cancérologie de l'Ouest

    Angers

  • CHU

    Bordeaux

  • Centre François Baclesse

    Caen, 14076

  • Centre Guillaume le Conquérant

    Le Havre

  • CH du Havre

    Le Havre

  • GHBS

    Lorient

  • Centre léon Bérard

    Lyon

  • Hôpitaux universitaires La Pitié Salpétrière - Charles Foix

    Paris

  • Institut Curie

    Paris

  • Centre Hospitalier Lyon Sud

    Pierre-Bénite

  • Centre Eugène Marquis

    Rennes

  • Centre Henri Becquerel

    Rouen

  • Institut de Cancérologie de l'Ouest

    Saint-Herblain

  • Institut Claudius Regaud

    Toulouse

Other trials in France

About this study

The Stupp protocol is the standard treatment of glioblastoma multiform (GBM) which prognosis remains poor.

The non-dividing nature of normal brain cells provides an opportunity to enhance the therapeutic ratio by combining radiation with inhibitors of replication-specific DNA repair pathways such poly(ADP-ribose) polymerase (PARP) inhibitors, thus inducing more cytotoxic effects of DNA-damage related to treatment modalities, including alkylating reagents like temozolomide (TMZ).

Read more

Olaparib, a potent PARP inhibitor, overcomes apoptotic resistance and sensitizes GBM cells for death receptor-mediated apoptosis induced by TRAIL (Tumor necrosis factor-Related Apoptosis Inducing Ligand). Moreover, inhibition of PARP activity increases cellular sensitivity to ionizing radiation: it was even suggested to be more pronounced in tumors than in normal tissue.

Lastly, progress in technical imaging and intensity-modulated-radiotherapy (IMRT) techniques provide new possibilities for sparing healthy tissues.

Read the detailed description

HGGs are the most common and most aggressive primary brain tumor. There is a real need to improve care management of GBM patients. Attempts to achieve cure by increasing radiation dose result in unacceptable neurotoxicity. As for radiosensitizers, they can exacerbate normal tissue damage.

Since GBM represent a rapidly dividing cell population within the nonreplicating normal brain, the therapeutic ratio may be enhanced by specific radiosensitization of proliferating cells. Resistance to apoptosis is a paramount issue in the treatment of HGG. Targeting PARP by the inhibitors like olaparib can reduce proliferation and lowers the apoptotic threshold of HGG (effect showed in vivo and in vitro).

In this context, we propose a phase I-IIa trail to investigate the toxicity and efficacy of olaparib and TMZ concomitantly with radiotherapy in first line treatment of unresectable high risk HGG.

Correlation between treatment response and tumor profiling will allow us to identify biomarkers that can be useful in treatment improvement and/or present a prognostic value. Then, the transfer of this approach will be evaluated in terms of compatibility with the requirements of diagnostic.

Being tested
Olaparib, Temozolomide (TMZ), IMRT (Intensity Modulated Radiation Therapy)
Medical subject headings
Glioma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • OlaparibDrug

    We propose 7 dose levels to reach the target dose of 400 mg per day (200 mg twice daily) of olaparib continuously DL1 (starting dose level) : Olaparib 50 mg Q12H Monday to wednesday DL2 : Olaparib 100mg Q12H Monday to wednesday DL3: Olaparib 100mg Q12H Monday to friday DL4 : Olaparib 200mg Q12H Monday to wednesday DL5: Olaparib 200mg Q12H Monday to friday DL6: Olaparib 200mg Q12H, continously

  • Temozolomide (TMZ)Drug

    TMZ will be given at the dose of 75mg/m²/day during radiotherapy period. TMZ will be re-introduced 4 weeks after the end of radiotherapy at the dose of 150mg/m²/day on days 1 to 5 every 28 days, for a total of 6 cycles.

  • IMRT (Intensity Modulated Radiation Therapy)Radiation

    Radiotherapy consists of fractionated focal irradiation at a dose of 2 Gy per fraction given once daily five days per week over 6 weeks, for a total dose of 60 Gy by 3D- Intensity-Modulated RT (IMRT)

Study groups in NCT03212742
Study groupRoleWhat they receive
IMRT - Temozolomide - OlaparibExperimentalThe therapeutic regimen will be divided into 2 different periods: * Radiotherapy period The patient will start IMRT (60Gy/30fr/6 weeks), TMZ(Temozolomide) chemotherapy (75mg/m²/day), and olaparib on the same day, on a Monday (day 1), within 6 weeks after surgery. The daily dose of TMZ (75 mg/m²) will be continued until the end of radiotherapy (6 weeks) and olaparib will be continued with the same dose until 4 weeks after the end of IMRT, as a single agent. * Maintenance period TMZ will then be re-introduced 4 weeks after the end of IMRT at the dose of 150 mg/m2/day on days 1 to 5 every 28 days, for a total of 6 cycles. Concomitantly, olaparib will be daily given at the maintenance dose level up to confirmed disease progression or unacceptable toxicities. We propose 7 dose levels to reach the target dose of 400 mg per day (200 mg twice daily) of olaparib continuously
Receives: Drug: Olaparib; Drug: Temozolomide (TMZ); Radiation: IMRT (Intensity Modulated Radiation Therapy)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. The Recommended Phase II Dose (RP2D) - Phase I

    The primary objective for the phase I is to determine the Recommended Phase II Dose (RP2D) of olaparib combined with the Stupp protocol (TMZ and concomitant fractionated radiotherapy: 60Gy/30 fractions/6 weeks) in first line treatment of patients with unresectable high-grade gliomas

    Measured: The RP2D will be evaluated 4 weeks after the end of radiotherapy

  2. Overall survival - Phase II

    The primary objective for the phase II is to assess the 12-month overall survival of the combination

    Measured: 12 months after the first administration of treatment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted11 Jul 2017
  2. Study start4 Sep 2017
  3. Primary completion13 Sep 2026 (estimated)
  4. Study completion31 Dec 2026 (estimated)

Resources

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 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Sequential
Masking
None (open label)
Enrolment
91 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03212742
Sponsor's protocol ID
OLA-TMZ-RTE-01
Acronym
OLA-TMZ-RTE-01
Status last verified
Nov 2025
First submitted
6 Jul 2017
Last updated
4 Dec 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • Lesueur P, Lequesne J, Grellard JM, Dugue A, Coquan E, Brachet PE, Geffrelot J, Kao W, Emery E, Berro DH, Castera L, Goardon N, Lacroix J, Lange M, Capel A, Leconte A, Andre B, Leger A, Lelaidier A, Clarisse B, Stefan D. Phase I/IIa study of concomitant radiotherapy with olaparib and temozolomide in unresectable or partially resectable glioblastoma: OLA-TMZ-RTE-01 trial protocol. BMC Cancer. 2019 Mar 4;19(1):198. doi: 10.1186/s12885-019-5413-y.

    PubMed 30832617

  • Stefan D, Lesueur P, Lequesne J, Feuvret L, Bronnimann C, Castera M, Brachet PE, Hrab I, Ducloie M, Lacroix J, Lecornu M, Braux G, Christy F, Sunyach MP, Cohen-Jonathan Moyal E, Kao W, Faisant M, Emery E, Grellard JM, Sichel F, Laurent C, Fontanilles M, Clarisse B. Olaparib, Temozolomide, and Concomitant Radiotherapy for Partially Resected or Biopsy-Only Glioblastoma First-Line Treatment: Results from the OLA-TMZ-RTE-01 Phase I Study. Clin Cancer Res. 2025 Apr 1;31(7):1212-1222. doi: 10.1158/1078-0432.CCR-24-2974.

    PubMed 39882966

  • Madhavan K, Balakrishnan I, Lakshmanachetty S, Pierce A, Sanford B, Fosmire S, Elajaili HB, Walker F, Wang D, Nozik ES, Mitra SS, Dahl NA, Vibhakar R, Venkataraman S. Venetoclax Cooperates with Ionizing Radiation to Attenuate Diffuse Midline Glioma Tumor Growth. Clin Cancer Res. 2022 Jun 1;28(11):2409-2424. doi: 10.1158/1078-0432.CCR-21-4002.

    PubMed 35344040

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Olaparib, Temozolomide (TMZ) and IMRT (Intensity Modulated Radiation Therapy) in people with Malignant Gliomas and Radiotherapy, run by Centre Francois Baclesse at 15 sites in France.

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 28 inclusion and 29 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: under way, not looking for participants, as of the sponsor's last update on 4 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 15 sites in France. 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 combined 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.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

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?

The Recommended Phase II Dose (RP2D) - Phase I (time frame: The RP2D will be evaluated 4 weeks after the end of radiotherapy). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03212742, which also lists 3 linked publications.

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 4 Dec 2025.

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