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

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

Official Title
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Randomized Phase II of Lomustine Versus Lomustine-Dasatinib in Patients With Recurrent Glioblastoma

Conditions
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Glioblastoma

Intervention / Treatment
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* Drug: Dasatinib
* Drug: Lomustine


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Dasatinib<br> | Drug: Dasatinib<br>* Tablets, Oral, 100 mg, Once or Twice daily (depending on safety cohort), Until progression or toxicity<br>* Other names: BMS-354825;|
| Active Comparator: Lomustine<br> | Drug: Lomustine<br>* Tablets, Oral, 110 mg/m², Every 6 weeks, until progression or toxicity<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), Deaths, and Discontinuations Due to AEs | 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. | 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). | 
| Number of Participants With Dose-limiting Toxicities (DLTs) | 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. | 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. | 
| Deaths Within 30 Days of Protocol Treatment Discontinuation |  | 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). | 
| Number of Participants With Worst Grade of Hematological Toxicity Per NCI CTCAE Version 3.0 Criteria | 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). | 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). | 
| Number of Participants With Worst Grade of Biochemistry Abnormality Per NCI CTCAE Version 3.0 Criteria | 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. | 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). |