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

Phase 1

Terminated

Conditions: Glioblastoma

Interventions: Drug: Dasatinib
Drug: Lomustine

Registration Number: NCT00948389

Lead Sponsor: Bristol-Myers Squibb

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

Detailed Description: Not available

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 28

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Dasatinib	Dasatinib	-
Lomustine	Lomustine	-

Primary Outcome Measures

Name	Time	Method
Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), Deaths, and Discontinuations Due to AEs	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.
Number of Participants With Dose-limiting Toxicities (DLTs)	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.
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	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).
Number of Participants With Worst Grade of Biochemistry Abnormality Per NCI CTCAE Version 3.0 Criteria	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.