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

Glioblastoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00948389
• Other study ID #: CA180-274
• Secondary ID: Protocol 2608320
• Status: Terminated
• Phase: Phase 1/Phase 2
• First received: July 28, 2009
• Last updated: August 27, 2012
• Start date: October 2009
• Est. completion date: May 2011

Study information

• Verified date: August 2012
• Source: Bristol-Myers Squibb
• Contact: n/a
• Is FDA regulated: No
• Health authority: European Union: European Medicines AgencyBelgium: Federal Agency for Medicinal Products and Health ProductsFrance: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)Germany: Federal Institute for Drugs and Medical DevicesIsrael: Israeli Health Ministry Pharmaceutical AdministrationItaly: National Monitoring Centre for Clinical Trials - Ministry of HealthNetherlands: The Central Committee on Research Involving Human Subjects (CCMO)Switzerland: SwissmedicUnited Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 28
• Est. completion date: May 2011
• Est. primary completion date: May 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Glioblastoma

Intervention

Drug:
• Dasatinib
Tablets, Oral, 100 mg, Once or Twice daily (depending on safety cohort), Until progression or toxicity
• Lomustine
Tablets, Oral, 110 mg/m², Every 6 weeks, until progression or toxicity

Locations

Country	Name	City	State
France	Local Institution	Paris Cedex
Italy	Local Institution	Bologna
Netherlands	Local Institution	Nijmegen
Netherlands	Local Institution	Rotterdam
Switzerland	Local Institution	Lausanne

Sponsors (2)

Lead Sponsor	Collaborator
Bristol-Myers Squibb	European Organisation for Research and Treatment of Cancer - EORTC

Countries where clinical trial is conducted

France,  Italy,  Netherlands,  Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Number of Participants With Disease Progression at 12 Months	As measured by brain magnetic resonance imaging.	12 months	No
Primary	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).	Yes
Primary	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.	Yes
Primary	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).	Yes
Primary	Number of Participants With Worst Grade of Hematological Toxicity Per NCI CTCAE Version 3.0 Criteria	Neutrophils (neutropenia): Grade (gr)1	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).	Yes
Primary	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).	Yes

External Links

•   BMS Clinical Trials Disclosure
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