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

This study has been terminated.

(Inability to meet protocol objectives)

Sponsor:

ClinicalTrials.gov Identifier:

NCT00948389

First Posted: July 29, 2009

Last Update Posted: August 31, 2012

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.

Collaborator:

European Organisation for Research and Treatment of Cancer - EORTC

Information provided by (Responsible Party):

Bristol-Myers Squibb

Purpose

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

Condition	Intervention	Phase
Glioblastoma	Drug: Dasatinib Drug: Lomustine	Phase 1 Phase 2


Study Type:	Interventional
Study Design:	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

Resource links provided by NLM:

Drug Information available for: Lomustine Dasatinib

Genetic and Rare Diseases Information Center resources: Glioblastoma Glioma Neuroepithelioma

U.S. FDA Resources

Further study details as provided by Bristol-Myers Squibb:

Primary Outcome Measures:

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.
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.
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). ]
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).
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:

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


Enrollment:	28
Study Start Date:	October 2009
Study Completion Date:	May 2011
Primary Completion Date:	May 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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

Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:	18 Years and older (Adult, Senior)
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

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

Additional Information:

BMS Clinical Trials Disclosure This link exits the ClinicalTrials.gov site

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 Submitted:	July 28, 2009
First Posted:	July 29, 2009
Results First Submitted:	July 25, 2012
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

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