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

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

Study Description

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

• 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

Arms and Interventions

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

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

• 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

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:

Investigator Inquiry form 

• 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
• 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