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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01124240
Recruitment Status : Unknown
Verified July 2011 by Northern Sydney and Central Coast Area Health Service.
Recruitment status was:  Recruiting
First Posted : May 17, 2010
Last Update Posted : July 26, 2011
Sponsor:
Collaborator:
Merck KGaA, Darmstadt, Germany
Information provided by:
Northern Sydney and Central Coast Area Health Service

Tracking Information
First Submitted Date  ICMJE May 13, 2010
First Posted Date  ICMJE May 17, 2010
Last Update Posted Date July 26, 2011
Study Start Date  ICMJE November 2009
Estimated Primary Completion Date November 2012   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 14, 2010)
12 month progression free survival [ Time Frame: 3 years ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 14, 2010)
  • Objective response [ Time Frame: 3 years ]
    MRI review
  • Toxicity [ Time Frame: 3 years ]
    Utilising NCI CTC v 3.0
  • Peripheral WBC MGMT modulation [ Time Frame: 3 years ]
    Blood collection and analysis
  • biomarker correlation with response [ Time Frame: 3 years ]
    using multiplex bioassay analysis
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Temozolomide and Procarbazine With Cilengitide for Patients With Glioblastoma Multiforme Without Methylation of the MGMT Promoter Gene
Official Title  ICMJE 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
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.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Newly Diagnosed Non Methylated Glioblastoma Multiforme Grade 4
Intervention  ICMJE Drug: 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.

Other Names:
  • Temozolomide
  • Procarbazine
Study Arms  ICMJE Not Provided
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Unknown status
Estimated Enrollment  ICMJE
 (submitted: May 14, 2010)
48
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE January 2014
Estimated Primary Completion Date November 2012   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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 [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.
  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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01124240
Other Study ID Numbers  ICMJE 0910259M
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Dr Helen Wheeler, Royal North Shore Hospital, Sydney, Australia
Study Sponsor  ICMJE Northern Sydney and Central Coast Area Health Service
Collaborators  ICMJE Merck KGaA, Darmstadt, Germany
Investigators  ICMJE Not Provided
PRS Account Northern Sydney and Central Coast Area Health Service
Verification Date July 2011

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP