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

NCT00948389 | Terminated Phase 1 Results

• 3 other identifiers: CA180-274Protocol 260832009-010576-21
• Study Type: interventional
• Target: 28
• Locations: 4 countries
• Sites: 5

Brief Summary

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

Conditions

Glioblastoma

Outcome Measures

Primary Outcomes (5)

• 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).

Other Outcomes (1)

• Number of Participants With Disease Progression at 12 Months

  12 months

Study Arms (2)

Dasatinib

ACTIVE COMPARATOR

Drug: Dasatinib

Lomustine

ACTIVE COMPARATOR

Drug: Lomustine

Interventions

Dasatinib DRUG

Tablets, Oral, 100 mg, Once or Twice daily (depending on safety cohort), Until progression or toxicity

Also known as: BMS-354825

Dasatinib

Lomustine DRUG

Tablets, Oral, 110 mg/m², Every 6 weeks, until progression or toxicity

Lomustine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Bristol-Myers Squibb: lead
• European Organisation for Research and Treatment of Cancer - EORTC: collaborator

Study Sites (5)

Local Institution

Paris, 75013, France

Location

Local Institution

Bologna, 40139, Italy

Location

Local Institution

Nijmegen, 6525 GA, Netherlands

Location

Local Institution

Rotterdam, 3075 EA, Netherlands

Location

Local Institution

Lausanne, 1011, Switzerland

Location

Related Links

• Investigator Inquiry form

MeSH Terms

Conditions

Glioblastoma

Interventions

Dasatinib; Lomustine

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines; Nitrosourea Compounds; Urea; Amides; Nitroso Compounds

Results Point of Contact

• Title: BMS Study Director
• Organization: Bristol-Myers Squibb

clinical.trials@bms.com

Study Officials

• Bristol-Myers Squibb

  Bristol-Myers Squibb

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 28, 2009
• First Posted: July 29, 2009
• Study Start: October 1, 2009
• Primary Completion: May 1, 2011
• Study Completion: May 1, 2011
• Last Updated: August 31, 2012
• Results First Posted: August 28, 2012

Record last verified: 2012-08

Locations

FR (1); NL (2); CH (1); IT (1)