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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01124240




Registration number
NCT01124240
Ethics application status
Date submitted
13/05/2010
Date registered
17/05/2010
Date last updated
26/07/2011

Titles & IDs
Public title
Temozolomide and Procarbazine With Cilengitide for Patients With Glioblastoma Multiforme Without Methylation of the MGMT Promoter Gene
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
Secondary ID [1] 0 0
0910259M
Universal Trial Number (UTN)
Trial acronym
ExCentric
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Newly Diagnosed Non Methylated Glioblastoma Multiforme Grade 4 0 0
Condition category
Condition code
Cancer 0 0 0 0
Brain

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Cilengitide

Treatment: Drugs: Cilengitide
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.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
12 month progression free survival
Timepoint [1] 0 0
3 years
Secondary outcome [1] 0 0
Objective response
Timepoint [1] 0 0
3 years
Secondary outcome [2] 0 0
Toxicity
Timepoint [2] 0 0
3 years
Secondary outcome [3] 0 0
Peripheral WBC MGMT modulation
Timepoint [3] 0 0
3 years
Secondary outcome [4] 0 0
biomarker correlation with response
Timepoint [4] 0 0
3 years

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
UNKNOWN
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/11/2009
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/01/2014
Actual
Sample size
Target
48
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 0 0
Royal North Shore Hospital - Sydney
Recruitment postcode(s) [1] 0 0
2065 - Sydney

Funding & Sponsors
Primary sponsor type
Other
Name
Northern Sydney and Central Coast Area Health Service
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
Merck KGaA, Darmstadt, Germany
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/study/NCT01124240
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT01124240