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

• Register: ClinicalTrials.gov
• Last refreshed on: 17 October 2012
• Main ID: NCT01124240
• Date of registration: 13/05/2010
• Primary sponsor: Northern Sydney and Central Coast Area Health Service
• Public title: Temozolomide and Procarbazine With Cilengitide for Patients With Glioblastoma Multiforme Without Methylation of the MGMT Promoter Gene ExCentric
• Scientific title: Phase 11 Study of Cilengitide in Combination With Concurrent Chemotherapy and Radiotherapy Followed by Protracted Daily Low Dose Temozolomide and Low Dose Procarbazine D1 - 20 in Newly Diagnosed Glioblastoma Without Methylation of the MGMT Promoter Gene
• Date of first enrolment: November 2009
• Target sample size: 48
• Recruitment status: Recruiting
• URL: http://clinicaltrials.gov/show/NCT01124240
• Study type: Interventional
• Study design: Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Countries of recruitment

Australia

Contacts

• Name: Sally McCowatt, Rn

Key inclusion & exclusion criteria

Inclusion Criteria:

1. 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.

2. Males or females =18 years of age.

3. Proven unmethylated MGMT gene promoter status, centrally assessed as part of the
screening for the CENTRIC trial.

4. 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.

5. 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).

6. Stable or decreasing dose of steroids for >5 days prior to randomization.

7. ECOG PS of 0-1.

8. Interval of =2 weeks but =7 weeks after surgery or biopsy before first administration
of study treatment.

9. Meets one of the following RPA classifications:

- Class III (age <50 years and ECOG PS 0).

- Class IV (meeting one of the following criteria:

1. Age <50 years and ECOG PS 1 or

2. Age =50 years, underwent prior partial or total tumor resection, Mini
Mental State Examination [MMSE]=27).

- Class V (meeting one of the following criteria:

1. Age =50 years and underwent prior partial or total tumour resection, MMSE
<27 or

2. Age =50 years and underwent prior tumor biopsy only).

10. Laboratory values (within 2 week prior to randomization):

- Absolute neutrophil count =1500/mm3.

- Platelets = 100,000/mm3.

- Creatinine =1.5 x upper limit of normal (ULN) or creatinine clearance rate =60
mL/min

- Prothrombin time (PT) international normalized ratio (INR) and partial
thromboplastin time (PTT) within normal limits.

- Hemoglobin =10 g/dL.

- Total bilirubin =1.5 x the ULN.

- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) = 2.5 x
ULN(except when attributable to anticonvulsants).

- Alkaline phosphatase = 2.5 x ULN.

Exclusion criteria

Subjects are not eligible for this study, if they fulfill one or more of the following
exclusion criteria:

1. Prior chemotherapy within the last 5 years.

2. Prior RTX of the head.

3. Receiving concurrent investigational agents or has received an investigational
agent(s) within the past 30 days prior to the first dose of Cilengitide .

4. Prior systemic antiangiogenic therapy.

5. Placement of Gliadel® wafer at surgery.

6. Treatment with a prohibited concomitant medication.

7. Planned surgery for other diseases (e.g. dental extraction).

8. History of recent peptic ulcer disease (endoscopically proven gastric ulcer, duodenal
ulcer, or esophageal ulcer) within 6 months of enrollment.

9. 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.

10. History of coagulation disorder associated with bleeding or recurrent thrombotic
events.

11. Clinically manifest myocardial insufficiency (NYHA III, IV) or history of myocardial
infarction during the past 6 months. Uncontrolled arterial hypertension.

12. Concurrent illness, including severe infection, which may jeopardize the ability of
the subject to receive the procedures outlined in this protocol with reasonable
safety.

13. Subject is pregnant (positive serum beta human chorionic gonadotropin [ß-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.

14. Current alcohol dependence or drug abuse.

15. Known hypersensitivity to the study treatment.

16. Legal incapacity or limited legal capacity.

17. Inability to undergo Gd-MRI.

18. Presence of any psychological, familial, sociological or geographical condition
potentially hampering compliance with the study protocol and follow-up schedule.

19. Signs and symptoms suggestive of transmissible spongiform encephalopathy, or of
family members who suffer(ed) from such.



Age minimum: 18 Years
Age maximum: N/A
Gender: Both

Health Condition(s) or Problem(s) studied

Newly Diagnosed Non Methylated Glioblastoma Multiforme Grade 4

Intervention(s)

Drug: Cilengitide

Primary Outcome(s)

12 month progression free survival [Time Frame: 3 years]

Secondary Outcome(s)

biomarker correlation with response [Time Frame: 3 years]

Objective response [Time Frame: 3 years]

Peripheral WBC MGMT modulation [Time Frame: 3 years]

Toxicity [Time Frame: 3 years]

Secondary ID(s)

0910259M

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Merck KGaA