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

Primary Purpose

Glioblastoma

Status
Terminated
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
Dasatinib
Lomustine
Sponsored by
Bristol-Myers Squibb
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Glioblastoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Local Institution
  • Local Institution
  • Local Institution
  • Local Institution
  • Local Institution

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Active Comparator

Arm Label

Dasatinib

Lomustine

Arm Description

Outcomes

Primary Outcome Measures

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.
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.
Deaths Within 30 Days of Protocol Treatment Discontinuation
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).
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.

Secondary Outcome Measures

Full Information

First Posted
July 28, 2009
Last Updated
August 27, 2012
Sponsor
Bristol-Myers Squibb
Collaborators
European Organisation for Research and Treatment of Cancer - EORTC
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1. Study Identification

Unique Protocol Identification Number
NCT00948389
Brief Title
Study of CCNU (Lomustine) Plus Dasatinib in Recurrent Glioblastoma (GBM)
Official Title
Randomized Phase II of Lomustine Versus Lomustine-Dasatinib in Patients With Recurrent Glioblastoma
Study Type
Interventional

2. Study Status

Record Verification Date
August 2012
Overall Recruitment Status
Terminated
Why Stopped
Inability to meet protocol objectives
Study Start Date
October 2009 (undefined)
Primary Completion Date
May 2011 (Actual)
Study Completion Date
May 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Bristol-Myers Squibb
Collaborators
European Organisation for Research and Treatment of Cancer - EORTC

4. Oversight

Data Monitoring Committee
No

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Glioblastoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
28 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Dasatinib
Arm Type
Active Comparator
Arm Title
Lomustine
Arm Type
Active Comparator
Intervention Type
Drug
Intervention Name(s)
Dasatinib
Other Intervention Name(s)
BMS-354825
Intervention Description
Tablets, Oral, 100 mg, Once or Twice daily (depending on safety cohort), Until progression or toxicity
Intervention Type
Drug
Intervention Name(s)
Lomustine
Intervention Description
Tablets, Oral, 110 mg/m², Every 6 weeks, until progression or toxicity
Primary Outcome Measure Information:
Title
Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), Deaths, and Discontinuations Due to AEs
Description
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.
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).
Title
Number of Participants With Dose-limiting Toxicities (DLTs)
Description
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.
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.
Title
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).
Title
Number of Participants With Worst Grade of Hematological Toxicity Per NCI CTCAE Version 3.0 Criteria
Description
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).
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).
Title
Number of Participants With Worst Grade of Biochemistry Abnormality Per NCI CTCAE Version 3.0 Criteria
Description
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.
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).
Other Pre-specified Outcome Measures:
Title
Number of Participants With Disease Progression at 12 Months
Description
As measured by brain magnetic resonance imaging.
Time Frame
12 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Bristol-Myers Squibb
Organizational Affiliation
Bristol-Myers Squibb
Official's Role
Study Director
Facility Information:
Facility Name
Local Institution
City
Paris Cedex
ZIP/Postal Code
75013
Country
France
Facility Name
Local Institution
City
Bologna
ZIP/Postal Code
40139
Country
Italy
Facility Name
Local Institution
City
Nijmegen
ZIP/Postal Code
6525 GA
Country
Netherlands
Facility Name
Local Institution
City
Rotterdam
ZIP/Postal Code
3075 EA
Country
Netherlands
Facility Name
Local Institution
City
Lausanne
ZIP/Postal Code
1011
Country
Switzerland

12. IPD Sharing Statement

Learn more about this trial

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

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