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|NCT03212742 : Phase I/IIa Study of Concomitant Radiotherapy With Olaparib and Temozolomide in Unresectable High Grade Gliomas Patients|
|Phase||Phase 1/Phase 2|
|Ages||Min: 18 Years Max: 70 Years|
- 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:
- 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
- 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
- Subjects affiliated to an appropriate social security system
- 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
- Previous enrolment in the present study
- Participation in another clinical trial protocol within 30 days prior to enrolment;
- 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
- 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
- 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
- For temozolomide treatment, patients with a known galactose intolerance, a Lapp
lactase deficit or a glucose or galactose malabsorption syndrome (rare hereditary
- 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).
|Links||Permanent Link to THIS page: http://virtualtrials.com/nct/display1trial.cfm?nct=NCT03212742
| Link to official Clinicaltrials.gov listing
Facility: Centre François Baclesse
Dinu STEFAN, MD
Dinu STEFAN, MD Phone: 33 2 31 45 50 50
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