Radiation therapy and concurrent plus adjuvant Temsirolimus (CCI-779) versus chemo-irradiation with Temozolomide in newly diagnosed glioblastoma without methylation of the MGMT gene promoter – a randomized multicenter, open-label, Phase II study

• Conditions: patients with newly diagnosed glioblastoma (GBM) without methylation of the DNA-repair enzyme O6-methylguanin-DNA-methyltransferase (MGMT) gene promoter; MedDRA version: 13.1Level: LLTClassification code 10006153Term: Brain tumorSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

• Registration Number: EUCTR2008-003003-31-DE
• Lead Sponsor: EORTC Headquarters

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2009-07-02
• Last Update Posted: 14 April 2014

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 108

Inclusion Criteria

•Present with newly diagnosed histologically proven supratentorial GBM (World Health Organization (WHO) grade IV). The histological diagnosis can be obtained either from an open brain biopsy or from a neurosurgical resection of the tumor.
•Patients must be at least 18 years of age.
•Estimated life expectancy of at least 12 weeks.

•Tumor tissue specimens (paraffin-embedded and/or frozen) from the GBM surgery or open biopsy must be available for central pathology review, MGMT status determination and exploratory analysis of PI3-K/Akt/mTOR targets (P70S6K).
•A 25 ml EDTA blood sample is also required.
•WHO-ECOG Performance Status of = 2.
•Clinically normal cardiac function without history of ischemic heart disease in the past 6 months and normal 12-lead electrocardiogram (ECG); no history of stroke.
•Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial.
•Patients of childbearing/ reproductive potential should use highly effective method of birth control as defined by the investigator. For example those which result in a low failure rate (i.e. less than 1% per year) when used consistently and correctly such as implants, injectables, combined oral contraceptives, some IDUs, sexual abstinence or vasectomised partner. For subjects using a hormonal contraceptive method, information regarding the product under evaluation and its potential effect on contraceptives should be addressed. Women with childbearing potential must have a negative serum pregnancy test (?-HCG) = 14 days prior to registration and can not be breastfeeding.
•Before patient registration, written informed consent must be given according to ICH/GCP, and national/local regulations.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

Patients will be excluded from the study if they meet any of the following criteria:
•Have had a prior malignancy within the last 5 years (other than adequately treated carcinoma in situ of the cervix, or non-melanoma skin cancer, with no subsequent evidence of recurrence).
•Having undergone only a stereotactic biopsy (open biopsy is allowed as ensuring sufficient tumor tissue yield).
•Unable to undergo Gd MRI.
•Have had chemotherapy within the last 5 years
•Prior chemotherapy for a brain tumor
•Prior RT of the head
•Are receiving concurrent administration of any other antitumor therapy
•Are using enzyme inducing anti convulsivants (in particular carbamazepine, phenobarbital and phenytoine) and are unable to discontinue use of these agents. Or any other strong inducers or inhibitors of CYP3A4.
•Planned surgery for other diseases (for example, dental extraction)
•Placement of Gliadel® wafer at surgery
•Have a serious concomitant systemic disorder (for example, active infection including HIV, or cardiac disease) that, in the opinion of the investigator, would compromise the patient’s ability to adhere to the protocol. Patients with a QTc prolongation >450/470 msec (males/females) and patients who have a congenital long-QT-syndrome in their own or family medical history should be excluded, at the investigator’s discretion.
•Known hypersensitivity to the study treatment
•Current alcohol dependence or drug abuse
•Legal incapacity or limited legal capacity
•Have received treatment within the last 30 days with a drug that has not received regulatory approval for any indication at the time of registration

Study & Design

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

Primary Outcome Measures

Name	Time	Method
Main Objective: The study’s primary objective is to document the activity profile of CCI-779 by the evaluation of OS12 in patients with newly diagnosed glioblastoma (GBM) without methylation of the MGMT gene promoter, treated with CCI-779 before and concomitantly to RT, followed by CCI-779 maintenance therapy.<br>;Secondary Objective: The secondary objectives of the study are as follows:<br>•Investigate safety and tolerability of the combination. <br>•Assess progression free survival and overall survival. <br>•Assess biomarkers in the tumor tissue relevant to CCI-779 and disease state, and their correlation to clinical outcome.<br>;Primary end point(s): Probability of Survival at 12 months (OS12)