Temozolomide and Procarbazine With Cilengitide for Patients With Glioblastoma Multiforme Without Methylation of the MGMT Promoter Gene

NCT01124240 | Unknown Phase 2 DMC

• 1 other identifier: 0910259M
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

Brief Summary

Cilengitide 2000 mg flat i.v. twice weekly is administered over a period of 18 months without interruption. Starting one week after the initiation of Cilengitide, RTX (60 Gy, 2 Gy per fraction) with concurrent daily temozolomide (60 mg/m2 p.o.) and daily procarbazine (PCB, 50 mg p.o. if BSA \< 1.7; 100 mg p.o. if BSA ≥ 1.7) is given over a period of 6 weeks (RTX Monday to Friday, both TMZ and PCB seven days a week). After a break of 4 weeks, adjuvant TMZ (50mg/m2 p.o in first cycle, 60 mg/m2 p.o. in subsequent cycles) and PCB (50 mg p.o. if BSA \< 1.7; 100 mg p.o. if BSA ≥ 1.7) are then given daily D1 to 20. This TMZ/PCB cycle is repeated every 28 days over a total period of 6 cycles.

Conditions

Newly Diagnosed Non Methylated Glioblastoma Multiforme Grade 4

Keywords

Glioblastoma Multiforme

Outcome Measures

Primary Outcomes (1)

• 12 month progression free survival

  3 years

Secondary Outcomes (4)

• Objective response

  3 years

• Toxicity

  3 years

• Peripheral WBC MGMT modulation

  3 years

• biomarker correlation with response

  3 years

Interventions

Cilengitide DRUG

Cilengitide 2000 mg flat i.v. twice weekly is administered over a period of 18 months without interruption. Starting one week after the initiation of Cilengitide, RTX (60 Gy, 2 Gy per fraction) with concurrent daily temozolomide (60 mg/m2 p.o.) and daily procarbazine (PCB, 50 mg p.o. if BSA \< 1.7; 100 mg p.o. if BSA ≥ 1.7) is given over a period of 6 weeks (RTX Monday to Friday, both TMZ and PCB seven days a week). After a break of 4 weeks, adjuvant TMZ (50mg/m2 p.o in first cycle, 60 mg/m2 p.o. in subsequent cycles) and PCB (50 mg p.o. if BSA \< 1.7; 100 mg p.o. if BSA ≥ 1.7) are then given daily D1 to 20. This TMZ/PCB cycle is repeated every 28 days over a total period of 6 cycles.

Also known as: Temozolomide, Procarbazine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Newly diagnosed supratentorial GBM (WHO Grade IV,including GBM subtypes, e.g. gliosarcoma), histopathologically confirmed by central assessment as part of the screening for the CENTRIC trial.
• Males or females ≥18 years of age.
• Proven unmethylated MGMT gene promoter status, centrally assessed as part of the screening for the CENTRIC trial.
• Written informed consent for the present trial obtained before undergoing any study-related activities. The informed consent also allows access to all information obtained during the screening for the CENTRIC trial, notably the result of the MGMT testing.
• Available post-operative Gd-MRI performed within \<48 hours after surgery (in case it was not possible to obtain a Gd-MRI within \<48 hours post surgery, a Gd-MRI is to be performed prior to randomization).
• Stable or decreasing dose of steroids for \>5 days prior to randomization.
• ECOG PS of 0-1.
• Interval of ≥2 weeks but ≤7 weeks after surgery or biopsy before first administration of study treatment.
• Meets one of the following RPA classifications:
• Class III (age \<50 years and ECOG PS 0).
• Class IV (meeting one of the following criteria:
• Age \<50 years and ECOG PS 1 or
• Age ≥50 years, underwent prior partial or total tumor resection, Mini Mental State Examination \[MMSE\]≥27).
• Class V (meeting one of the following criteria:
• Age ≥50 years and underwent prior partial or total tumour resection, MMSE \<27 or

You may not qualify if:

• Prior chemotherapy within the last 5 years.
• Prior RTX of the head.
• Receiving concurrent investigational agents or has received an investigational agent(s) within the past 30 days prior to the first dose of Cilengitide .
• Prior systemic antiangiogenic therapy.
• Placement of Gliadel® wafer at surgery.
• Treatment with a prohibited concomitant medication.
• Planned surgery for other diseases (e.g. dental extraction).
• History of recent peptic ulcer disease (endoscopically proven gastric ulcer, duodenal ulcer, or esophageal ulcer) within 6 months of enrollment.
• History of malignancy. Subjects with curatively treated cervical carcinoma in situ or basal cell carcinoma of the skin, or subjects who have been free of other malignancies for ≥ 5 years are eligible for this study.
• History of coagulation disorder associated with bleeding or recurrent thrombotic events.
• Clinically manifest myocardial insufficiency (NYHA III, IV) or history of myocardial infarction during the past 6 months. Uncontrolled arterial hypertension.
• Concurrent illness, including severe infection, which may jeopardize the ability of the subject to receive the procedures outlined in this protocol with reasonable safety.
• Subject is pregnant (positive serum beta human chorionic gonadotropin \[β-HCG\] test at screening) or is currently breast-feeding, anticipates becoming pregnant/ impregnating their partner during the study or within 6 months after study participation, or subject does not agree to follow acceptable methods of birth control, such as hormonal contraception, intra-uterine pessar, condoms or sterilization, to avoid conception during the study and for at least 6 months after receiving the last dose of study treatment.
• Current alcohol dependence or drug abuse.
• Known hypersensitivity to the study treatment.

Sponsors & Collaborators

• Northern Sydney and Central Coast Area Health Service: lead
• Merck KGaA, Darmstadt, Germany: collaborator

Study Sites (1)

Royal North Shore Hospital

Sydney, New South Wales, 2065, Australia

RECRUITING

MeSH Terms

Conditions

Glioblastoma

Interventions

Cilengitide; Temozolomide; Procarbazine

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Benzamides; Amides; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: May 13, 2010
• First Posted: May 17, 2010
• Study Start: November 1, 2009
• Primary Completion: November 1, 2012
• Study Completion: January 1, 2014
• Last Updated: July 26, 2011

Record last verified: 2011-07

Locations

AU (1)