Study of CCNU (Lomustine) Plus Dasatinib in Recurrent Glioblastoma (GBM)

This study has been terminated.
(Inability to meet protocol objectives)
Sponsor:
Collaborator:
European Organisation for Research and Treatment of Cancer - EORTC
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT00948389
First received: July 28, 2009
Last updated: August 27, 2012
Last verified: August 2012
  Purpose

To determine whether dasatinib plus lomustine are effective for treatment of recurrent glioblastoma


Condition Intervention Phase
Glioblastoma
Drug: Dasatinib
Drug: Lomustine
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Randomized Phase II of Lomustine Versus Lomustine-Dasatinib in Patients With Recurrent Glioblastoma

Resource links provided by NLM:


Further study details as provided by Bristol-Myers Squibb:

Primary Outcome Measures:
  • Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), Deaths, and Discontinuations Due to AEs [ Time Frame: Assessed at baseline, every 2 weeks during cycles 1-6 (6-week cycles), and every 6 weeks after cycle 6. Median number of cycles = 1.0 (range: 1.0 - 7.0). ] [ Designated as safety issue: Yes ]
    SAE=any untoward medical event that results in death, persistent or significant disability/incapacity, or drug dependency or abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires inpatient hospitalization or prolongation. AE=any new untoward medical occurrence or worsening of a preexisting medical condition that does not necessarily have a causal relationship with this treatment. Treatment-related(Tx-R)=certainly, probably, possibly related and unknown relationship to study drug. AE grades(Gr) 1=Mild; 2=Moderate; 3=Severe; 4=Life-threatening.

  • Number of Participants With Dose-limiting Toxicities (DLTs) [ Time Frame: The duration for observation of DLT was 2 6-week cycles in participants with escalated dose (QD to BID) and 1 6 -week cycle for participants starting with BID regime. For participants receiving dasatinib at 150 mg, DLTs were only documented over cycle 1. ] [ Designated as safety issue: Yes ]
    Grades (gr) according to National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI CTCAE), version 3.0. DLTs were defined as adverse drug reactions as follows: absolute neutrophil counts <0.5x10^9/L (gr4) lasting for 7 consecutive days; febrile neutropenia (neutrophil count <1x10^9/L and fever of >=38.5°C); thrombocytopenia (gr4); any gr3/4 nonhematological toxicity except nausea, vomiting and fever which could be rapidly controlled with appropriate measures; any toxicity which did not allow administering at least 70% of the intended dose intensity for both agents.

  • Deaths Within 30 Days of Protocol Treatment Discontinuation [ Time Frame: From time of randomization through within 30 days after protocol treatment discontinuation. Median (full range) number of 6-week treatment cycles was 1.0 (1.0-7.0). ] [ Designated as safety issue: Yes ]
  • Number of Participants With Worst Grade of Hematological Toxicity Per NCI CTCAE Version 3.0 Criteria [ Time Frame: Assessed at baseline, every 2 weeks during cycles 1-6 (6-week cycles), and every 6 weeks after cycle 6. Median number of cycles = 1.0 (range: 1.0 - 7.0). ] [ Designated as safety issue: Yes ]
    Neutrophils (neutropenia): Grade (gr)1 <LLN-1500/mm3; Gr2 <1500-1000/mm3; Gr3 <1000-500/mm3; Gr4 <500/mm3. Leukocytes (leukopenia): Gr1 <LLN-3000/mm3; Gr2 <3000-2000/mm3; Gr3 <2000-1000/mm3; Gr4 <1000/mm3. Lymphocytes (lymphocytopenia): Gr1 <LLN-800/mm3; Gr2 <800-500/mm3; Gr3 <500-200/mm3; Gr4 <200/mm3. Platelets (thrombocytopenia): Gr1 <LLN-75,000/mm3; Gr2 <75,000-50,000/mm3; Gr3 <50,000-25,000/mm3; Gr4 <25,000/mm3. Hemoglobin (anemia): Gr1 <LLN-10.0 g/dL; Gr2 <10.0-8.0 g/dL; Gr3 <8.0-6.5 g/dL; Gr4 <6.5 g/dL. LLN/ULN=lower/upper limit of normal (normal ranges may vary by local laboratories).

  • Number of Participants With Worst Grade of Biochemistry Abnormality Per NCI CTCAE Version 3.0 Criteria [ Time Frame: Assessed at baseline, every 2 weeks during cycles 1-6 (6-week cycles), and every 6 weeks after 6 cycles. Median number of cycles = 1.0 (range: 1.0 - 7.0). ] [ Designated as safety issue: Yes ]
    Grades (gr) 1=mild; gr2=moderate; gr3=severe; gr4=life-threatening. For details of NCI CTCAE laboratory values for each grade, please refer to http://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm#ctc_30. Low Potassium=Hypokalemia, High Potassium=Hyperkalemia, Low Sodium=Hyponatremia, Low Calcium=Hypocalcemia, High Bilirubin=Hyperbilirubinemia, low phosphatase=Hypophosphatemia, Low Potassium=Hypokalemia.


Other Outcome Measures:
  • Number of Participants With Disease Progression at 12 Months [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    As measured by brain magnetic resonance imaging.


Enrollment: 28
Study Start Date: October 2009
Study Completion Date: May 2011
Primary Completion Date: May 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Dasatinib Drug: Dasatinib
Tablets, Oral, 100 mg, Once or Twice daily (depending on safety cohort), Until progression or toxicity
Other Name: BMS-354825
Active Comparator: Lomustine Drug: Lomustine
Tablets, Oral, 110 mg/m², Every 6 weeks, until progression or toxicity

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients with histological or cytological proven glioblastoma multiforme
  • Recurrent or progressive disease documented by magnetic resonance imaging (MRI)
  • World Health Organization (WHO) Performance status 0 - 2
  • Patient may have been operated for recurrence
  • For non operated patients, recurrent disease must be at least one bidimensionally measurable target lesion with one diameter of at least 2cm
  • Patients must be on a stable or decreasing dose of corticosteroids for at least 1 week prior to baseline MRI

Exclusion Criteria:

  • Patients with histological or cytological proven glioblastoma multiforme
  • Completion of radiotherapy to the brain less than 3 months prior to registration/randomization
  • Prior treatment with high dose radiotherapy, stereotactic radiosurgery or internal radiation therapy
  • Previous or current malignancy at other sites within prior 3 years
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00948389

Locations
France
Local Institution
Paris Cedex, France, 75013
Italy
Local Institution
Bologna, Italy, 40139
Netherlands
Local Institution
Nijmegen, Netherlands, 6525 GA
Local Institution
Rotterdam, Netherlands, 3075 EA
Switzerland
Local Institution
Lausanne, Switzerland, 1011
Sponsors and Collaborators
Bristol-Myers Squibb
European Organisation for Research and Treatment of Cancer - EORTC
Investigators
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
  More Information

Additional Information:
No publications provided

Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT00948389     History of Changes
Other Study ID Numbers: CA180-274, Protocol 26083, 2009-010576-21
Study First Received: July 28, 2009
Results First Received: July 25, 2012
Last Updated: August 27, 2012
Health Authority: European Union: European Medicines Agency
Belgium: Federal Agency for Medicinal Products and Health Products
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Federal Institute for Drugs and Medical Devices
Israel: Israeli Health Ministry Pharmaceutical Administration
Italy: National Monitoring Centre for Clinical Trials - Ministry of Health
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
Switzerland: Swissmedic
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Additional relevant MeSH terms:
Glioblastoma
Astrocytoma
Glioma
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Germ Cell and Embryonal
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Dasatinib
Lomustine
Alkylating Agents
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protein Kinase Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014