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

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ClinicalTrials.gov Identifier: NCT00948389
Recruitment Status : Terminated (Inability to meet protocol objectives)
First Posted : July 29, 2009
Results First Posted : August 28, 2012
Last Update Posted : August 31, 2012
Sponsor:
Collaborator:
European Organisation for Research and Treatment of Cancer - EORTC
Information provided by (Responsible Party):
Bristol-Myers Squibb

Study Description
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Brief Summary:
To determine whether dasatinib plus lomustine are effective for treatment of recurrent glioblastoma

Condition or disease Intervention/treatment Phase
Glioblastoma Drug: Dasatinib Drug: Lomustine Phase 1 Phase 2

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 28 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Randomized Phase II of Lomustine Versus Lomustine-Dasatinib in Patients With Recurrent Glioblastoma
Study Start Date : October 2009
Actual Primary Completion Date : May 2011
Actual Study Completion Date : May 2011

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Arms and Interventions
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Arm Intervention/treatment
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


Outcome Measures
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Primary Outcome Measures :
  1. 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). ]
    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.

  2. 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. ]
    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.

  3. 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). ]
  4. 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). ]
    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).

  5. 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). ]
    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:
  1. Number of Participants With Disease Progression at 12 Months [ Time Frame: 12 months ]
    As measured by brain magnetic resonance imaging.


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
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
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): 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
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Additional Information:
Investigator Inquiry form  This link exits the ClinicalTrials.gov site For FDA Safety Alerts and Recalls refer to the following link: http://www.fda.gov/MEDWATCH/safety.htm  This link exits the ClinicalTrials.gov site

Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT00948389     History of Changes
Other Study ID Numbers: CA180-274
Protocol 26083 ( Other Identifier: EORTC )
2009-010576-21 ( EudraCT Number )
First Posted: July 29, 2009    Key Record Dates
Results First Posted: August 28, 2012
Last Update Posted: August 31, 2012
Last Verified: August 2012

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