A phase II study of olaparib in recurrent IDH mutated high grade gliomas OLAGLI

Phase 1

• Conditions: patients with recurrent IDHm HGGs.; MedDRA version: 20.0 Level: PT Classification code 10018338 Term: Glioma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

• Registration Number: EUCTR2018-002584-25-FR
• Lead Sponsor: HOSPICES CIVILS DE LYO

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2018-11-06
• Last Update Posted: 28 February 2019

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: Not specified
• Target Recruitment: 35

Inclusion Criteria

21.Affiliation to a French social security system (recipient or assign) excluding AME.
22.Histological confirmation of grade III or IV high-grade glioma or evidence of anaplastic transformation (based on histological or radiological analysis) of a previous grade II glioma
23.Tumor is mutated for IDH1 or IDH2 gene (detected by R132HIDH immunochemistry or IDH1/IDH2 sequencing)
24.Recurrence after radiotherapy and at least one line of alkylating chemotherapy (Temozolomide or PCV (Procarbazine, CCNU, Vincristine) (Surgery at recurrence is allowed before trial inclusion)
25.Recurrence occurring more than 12 weeks from the end of the radiotherapy or occurring outside the irradiated volume
26.Provision of informed consent prior to any study specific procedures
27.Age = 18 years old
28.Patients must have normal organ and bone marrow function measured within 28 days prior to administration of study treatment as defined below:
?Haemoglobin = 10.0 g/dL with no blood transfusion in the past 28 days
?Absolute neutrophil count (ANC) = 1.5 x 109/L
?Platelet count = 100 x 109/L
?Total bilirubin = 1.5 x institutional upper limit of normal (ULN)
?Aspartate aminotransferase (AST) (Serum Glutamic Oxaloacetic Transaminase (SGOT)) / Alanine aminotransferase (ALT) (Serum Glutamic Pyruvate Transaminase (SGPT)) = 2.5 x institutional upper limit of normal
?Patients must have creatinine clearance estimated of =51 mL/min using the Cockcroft-Gault equation or based on a 24 hour urine test :
Estimated creatinine clearance =(140-age [years]) x weight (kg) (x F)a
serum creatinine (mg/dL) x 72
a where F=0.85 for females and F=1 for males.

29.KPS = 70
30.Patients must have a life expectancy = 16 weeks.
31.Postmenopausal or evidence of non-childbearing status for women of childbearing potential: negative urine or serum pregnancy test within 28 days of study treatment and confirmed prior to treatment on day 1.
Postmenopausal is defined as:
?Amenorrheic for 1 year or more following cessation of exogenous hormonal treatments
?Luteinizing hormone (LH) and Follicle stimulating hormone (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
?surgical sterilisation (bilateral oophorectomy or hysterectomy)

32.Female patients of child bearing potential and male patients with partners of child bearing potential, who are sexually active, must agree to the use of two highly effective forms of contraception. This should be started from the signing of the informed consent and continue throughout period of taking study treatment and for 1 month (female patients)/3 months (male patients) after last dose of study drug
33.Patients is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations.
34.Except in patients who undergo re-surgery, radiologically measurable disease based on RA

Exclusion Criteria

37.Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site)
38.Previous enrolment in the present study
39.Participation in another clinical study with an investigational product during the last month
40.Any previous treatment with PARP inhibitor, including olaparib.
41.Other malignancy unless curatively treated with no evidence of disease for =5 years except: adequately treated non-melanoma skin cancer, curatively treated in situ cancer of the cervix, ductal carcinoma in situ (DCIS), Stage 1, grade 1 endometrial carcinoma. Patients with a history of localised triple negative breast cancer may be eligible, provided they completed their adjuvant chemotherapy more than three years prior to registration, and that the patient remains free of recurrent or metastatic disease
42.Resting ECG indicating uncontrolled, potentially reversible cardiac conditions, as judged by the investigator (eg., unstable ischemia, uncontrolled symptomatic arrhythmia, congestive heart failure, QTcF prolongation >500 ms, electrolyte disturbances, etc.), or patients with congenital long QT syndrome.
43.Patients receiving any systemic chemotherapy or radiotherapy (except for palliative reasons) within 3 weeks prior to study treatment
44.Concomitant use of known strong CYP3A inhibitors (eg. itraconazole, telithromycin, clarithromycin, protease inhibitors boosted with ritonavir or cobicistat, indinavir, saquinavir, nelfinavir, boceprevir, telaprevir) or moderate CYP3A inhibitors (eg. ciprofloxacin, erythromycin, diltiazem, fluconazole, verapamil). The required washout period prior to starting olaparib is 2 weeks.
45.Concomitant use of known strong (eg. phenobarbital, enzalutamide, phenytoin, rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine and St John’s Wort ) or moderate CYP3A inducers (eg. bosentan, efavirenz, modafinil). The required washout period prior to starting olaparib is 5 weeks for enzalutamide or phenobarbital and 3 weeks for other agents.
46.Persistent toxicities (>Common Terminology Criteria for Adverse Event (CTCAE) grade 2) caused by previous cancer therapy, excluding alopecia.
47.Patients with myelodysplastic syndrome/acute myeloid leukaemia or with features suggestive of MDS/AML.
48.Major surgery within 2 weeks of starting study treatment and patients must have recovered from any effects of any major surgery.
49.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, superior vena cava syndrome, extensive interstitial bilateral lung disease on High Resolution Computed Tomography (HRCT) scan or any psychiatric disorder that prohibits obtaining informed consent.
50.Patients unable to swallow orally administered medication and patients with gastrointestinal disorders likely to interfere with absorption of the study medication.
51.Breast feeding women.
52.Immunocompromised patients, e.g., patients who are known to be

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified