Trial Outcomes & Findings for Study of CCNU (Lomustine) Plus Dasatinib in Recurrent Glioblastoma (GBM) (NCT NCT00948389)
NCT ID: NCT00948389
Last Updated: 2012-08-31
Results Overview
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.
Recruitment status
TERMINATED
Study phase
PHASE1/PHASE2
Target enrollment
28 participants
Primary outcome timeframe
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).
Results posted on
2012-08-31
Participant Flow
Of 28 participants enrolled in this study, 26 received treatment.
Participant milestones
| Measure |
Dasatinib, 100 mg QD/100 mg BID + Lomustine, 110 mg/m^2
Dose level 1A. Cycle 1: Dasatinib, 100 mg once daily (QD). Cycle 2: Dasatinib, 100 mg twice daily (BID), plus lomustine, 110 mg/m\^2.
|
Dasatinib, 100 mg QD/100 mg BID + Lomustine, 90 mg/m^2
Dose level 1B. Cycle 1: Dasatinib,100 mg QD. Cycle 2: 100 mg BID, plus lomustine, 90 mg/m\^2.
|
Dasatinib, 100 mg BID + Lomustine, 90 mg/m^2
Dose level 2. Dasatinib, 100 mg BID plus lomustine, 90 mg/m\^2
|
Dasatinib, 150 mg/d + Lomustine, 90 mg/m^2
Dose level 3A: Dasatinib, 150 mg/d (100 mg AM and 50 mg PM), plus lomustine, 90 mg/m\^2
|
Dasatinib, 100 mg/d QD + Lomustine, 90 mg/m^2
Dose Level 3B: Dasatinib, 100 mg/d QD plus lomustine, 90 mg/m\^2
|
|---|---|---|---|---|---|
|
Overall Study
STARTED
|
6
|
3
|
7
|
9
|
1
|
|
Overall Study
COMPLETED
|
0
|
0
|
0
|
0
|
0
|
|
Overall Study
NOT COMPLETED
|
6
|
3
|
7
|
9
|
1
|
Reasons for withdrawal
| Measure |
Dasatinib, 100 mg QD/100 mg BID + Lomustine, 110 mg/m^2
Dose level 1A. Cycle 1: Dasatinib, 100 mg once daily (QD). Cycle 2: Dasatinib, 100 mg twice daily (BID), plus lomustine, 110 mg/m\^2.
|
Dasatinib, 100 mg QD/100 mg BID + Lomustine, 90 mg/m^2
Dose level 1B. Cycle 1: Dasatinib,100 mg QD. Cycle 2: 100 mg BID, plus lomustine, 90 mg/m\^2.
|
Dasatinib, 100 mg BID + Lomustine, 90 mg/m^2
Dose level 2. Dasatinib, 100 mg BID plus lomustine, 90 mg/m\^2
|
Dasatinib, 150 mg/d + Lomustine, 90 mg/m^2
Dose level 3A: Dasatinib, 150 mg/d (100 mg AM and 50 mg PM), plus lomustine, 90 mg/m\^2
|
Dasatinib, 100 mg/d QD + Lomustine, 90 mg/m^2
Dose Level 3B: Dasatinib, 100 mg/d QD plus lomustine, 90 mg/m\^2
|
|---|---|---|---|---|---|
|
Overall Study
Disease Progression/Relapse/Death
|
3
|
3
|
7
|
8
|
1
|
|
Overall Study
Thrombocytopenia, Grade 4
|
2
|
0
|
0
|
1
|
0
|
|
Overall Study
Both Progression and Toxicity
|
1
|
0
|
0
|
0
|
0
|
Baseline Characteristics
Study of CCNU (Lomustine) Plus Dasatinib in Recurrent Glioblastoma (GBM)
Baseline characteristics by cohort
| Measure |
Dose Level 1A
n=6 Participants
Dasatinib: 100 mg once daily (QD) cycle 1 / 100 mg twice daily (BID) cycle 2 + lomustine (CCNU): 110 mg/m²
|
Dose Level 1B
n=3 Participants
Dasatinib: 100 mg QD / 100mg BID + CCNU: 90 mg/m²
|
Dose Level 2
n=7 Participants
Dasatinib: 100 mg BID + CCNU: 90 mg/m²
|
Dose Level 3A
n=9 Participants
Dasatinib: 150 mg/day (100 mg AM and 50 mg PM) + CCNU: 90 mg/m²
|
Dose Level 3B
n=1 Participants
Dasatinib: 100 mg/day (QD) + CCNU: 90 mg/m²
|
Total
n=26 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|---|
|
Age Continuous
|
58.8 years
n=5 Participants
|
57.7 years
n=7 Participants
|
53.6 years
n=5 Participants
|
49.7 years
n=4 Participants
|
51.1 years
n=21 Participants
|
54.8 years
n=10 Participants
|
|
Sex: Female, Male
Female
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
3 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
6 Participants
n=10 Participants
|
|
Sex: Female, Male
Male
|
5 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
6 Participants
n=4 Participants
|
1 Participants
n=21 Participants
|
20 Participants
n=10 Participants
|
|
Histological Diagnosis of Primary Disease
glioblastoma multiforme
|
6 participants
n=5 Participants
|
2 participants
n=7 Participants
|
5 participants
n=5 Participants
|
8 participants
n=4 Participants
|
1 participants
n=21 Participants
|
22 participants
n=10 Participants
|
|
Histological Diagnosis of Primary Disease
glioblastoma w/ oligodendroglial component
|
0 participants
n=5 Participants
|
1 participants
n=7 Participants
|
2 participants
n=5 Participants
|
1 participants
n=4 Participants
|
0 participants
n=21 Participants
|
4 participants
n=10 Participants
|
|
Eastern Cooperative Oncology Group (ECOG) Performance Status
Grade 0
|
6 participants
n=5 Participants
|
2 participants
n=7 Participants
|
1 participants
n=5 Participants
|
4 participants
n=4 Participants
|
1 participants
n=21 Participants
|
14 participants
n=10 Participants
|
|
Eastern Cooperative Oncology Group (ECOG) Performance Status
Grade 1
|
0 participants
n=5 Participants
|
1 participants
n=7 Participants
|
5 participants
n=5 Participants
|
4 participants
n=4 Participants
|
0 participants
n=21 Participants
|
10 participants
n=10 Participants
|
|
Eastern Cooperative Oncology Group (ECOG) Performance Status
Grade 2
|
0 participants
n=5 Participants
|
0 participants
n=7 Participants
|
1 participants
n=5 Participants
|
1 participants
n=4 Participants
|
0 participants
n=21 Participants
|
2 participants
n=10 Participants
|
PRIMARY outcome
Timeframe: 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).Population: All treated participants
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.
Outcome measures
| Measure |
Dasatinib, 100 mg QD/100 mg BID + Lomustine, 110 mg/m^2
n=6 Participants
Dose level 1A. Cycle 1: Dasatinib, 100 mg once daily (QD). Cycle 2: Dasatinib, 100 mg twice daily (BID), plus lomustine, 110 mg/m\^2.
|
Dasatinib, 100 mg QD/100 mg BID + Lomustine, 90 mg/m^2
n=3 Participants
Dose level 1B. Cycle 1: Dasatinib,100 mg QD. Cycle 2: 100 mg BID, plus lomustine, 90 mg/m\^2
|
Dasatinib, 100 mg BID + Lomustine, 90 mg/m^2
n=7 Participants
Dose level 2. Dasatinib, 100 mg BID plus lomustine, 90 mg/m\^2
|
Dasatinib, 150 mg/d + Lomustine, 90 mg/m^2
n=9 Participants
Dose level 3A: Dasatinib, 150 mg/d (100 mg AM and 50 mg PM), plus lomustine, 90 mg/m\^2
|
Dasatinib, 100 mg/d QD + Lomustine, 90 mg/m^2
n=1 Participants
Dose Level 3B: Dasatinib, 100 mg/d QD plus lomustine, 90 mg/m\^2
|
|---|---|---|---|---|---|
|
Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), Deaths, and Discontinuations Due to AEs
At Least 1 Tx-R Gr 3/4 AE
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
|
Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), Deaths, and Discontinuations Due to AEs
Deaths within 30 days of Tx Discontinuation
|
1 participants
|
0 participants
|
1 participants
|
0 participants
|
0 participants
|
|
Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), Deaths, and Discontinuations Due to AEs
Tx-R Deaths within 30 days of Tx Discontinuation
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
|
Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), Deaths, and Discontinuations Due to AEs
At Least 1 SAE
|
5 participants
|
1 participants
|
4 participants
|
4 participants
|
0 participants
|
|
Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), Deaths, and Discontinuations Due to AEs
At Least 1 Tx-R SAE
|
4 participants
|
0 participants
|
1 participants
|
1 participants
|
0 participants
|
|
Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), Deaths, and Discontinuations Due to AEs
Discontinuations Due to AEs
|
3 participants
|
0 participants
|
0 participants
|
1 participants
|
0 participants
|
|
Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), Deaths, and Discontinuations Due to AEs
At Least 1 AE
|
6 participants
|
3 participants
|
7 participants
|
9 participants
|
1 participants
|
|
Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), Deaths, and Discontinuations Due to AEs
At Least 1 Gr 3/4 AE
|
2 participants
|
2 participants
|
4 participants
|
4 participants
|
0 participants
|
|
Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), Deaths, and Discontinuations Due to AEs
At Least 1 Tx-R AE
|
5 participants
|
2 participants
|
5 participants
|
7 participants
|
1 participants
|
PRIMARY outcome
Timeframe: 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.Population: Evaluable Participants: subset of participants used to decide on dose escalations. Participants were assessable if they completed the period for DLT observation.
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.
Outcome measures
| Measure |
Dasatinib, 100 mg QD/100 mg BID + Lomustine, 110 mg/m^2
n=5 Participants
Dose level 1A. Cycle 1: Dasatinib, 100 mg once daily (QD). Cycle 2: Dasatinib, 100 mg twice daily (BID), plus lomustine, 110 mg/m\^2.
|
Dasatinib, 100 mg QD/100 mg BID + Lomustine, 90 mg/m^2
Dose level 1B. Cycle 1: Dasatinib,100 mg QD. Cycle 2: 100 mg BID, plus lomustine, 90 mg/m\^2
|
Dasatinib, 100 mg BID + Lomustine, 90 mg/m^2
n=5 Participants
Dose level 2. Dasatinib, 100 mg BID plus lomustine, 90 mg/m\^2
|
Dasatinib, 150 mg/d + Lomustine, 90 mg/m^2
n=9 Participants
Dose level 3A: Dasatinib, 150 mg/d (100 mg AM and 50 mg PM), plus lomustine, 90 mg/m\^2
|
Dasatinib, 100 mg/d QD + Lomustine, 90 mg/m^2
Dose Level 3B: Dasatinib, 100 mg/d QD plus lomustine, 90 mg/m\^2
|
|---|---|---|---|---|---|
|
Number of Participants With Dose-limiting Toxicities (DLTs)
|
3 participants
|
—
|
3 participants
|
4 participants
|
—
|
PRIMARY outcome
Timeframe: 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).Population: Treated participants
Outcome measures
| Measure |
Dasatinib, 100 mg QD/100 mg BID + Lomustine, 110 mg/m^2
n=6 Participants
Dose level 1A. Cycle 1: Dasatinib, 100 mg once daily (QD). Cycle 2: Dasatinib, 100 mg twice daily (BID), plus lomustine, 110 mg/m\^2.
|
Dasatinib, 100 mg QD/100 mg BID + Lomustine, 90 mg/m^2
n=3 Participants
Dose level 1B. Cycle 1: Dasatinib,100 mg QD. Cycle 2: 100 mg BID, plus lomustine, 90 mg/m\^2
|
Dasatinib, 100 mg BID + Lomustine, 90 mg/m^2
n=7 Participants
Dose level 2. Dasatinib, 100 mg BID plus lomustine, 90 mg/m\^2
|
Dasatinib, 150 mg/d + Lomustine, 90 mg/m^2
n=9 Participants
Dose level 3A: Dasatinib, 150 mg/d (100 mg AM and 50 mg PM), plus lomustine, 90 mg/m\^2
|
Dasatinib, 100 mg/d QD + Lomustine, 90 mg/m^2
n=1 Participants
Dose Level 3B: Dasatinib, 100 mg/d QD plus lomustine, 90 mg/m\^2
|
|---|---|---|---|---|---|
|
Deaths Within 30 Days of Protocol Treatment Discontinuation
|
1 participants
|
0 participants
|
1 participants
|
0 participants
|
0 participants
|
PRIMARY outcome
Timeframe: 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).Population: Treated participants
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).
Outcome measures
| Measure |
Dasatinib, 100 mg QD/100 mg BID + Lomustine, 110 mg/m^2
n=6 Participants
Dose level 1A. Cycle 1: Dasatinib, 100 mg once daily (QD). Cycle 2: Dasatinib, 100 mg twice daily (BID), plus lomustine, 110 mg/m\^2.
|
Dasatinib, 100 mg QD/100 mg BID + Lomustine, 90 mg/m^2
n=3 Participants
Dose level 1B. Cycle 1: Dasatinib,100 mg QD. Cycle 2: 100 mg BID, plus lomustine, 90 mg/m\^2
|
Dasatinib, 100 mg BID + Lomustine, 90 mg/m^2
n=7 Participants
Dose level 2. Dasatinib, 100 mg BID plus lomustine, 90 mg/m\^2
|
Dasatinib, 150 mg/d + Lomustine, 90 mg/m^2
n=9 Participants
Dose level 3A: Dasatinib, 150 mg/d (100 mg AM and 50 mg PM), plus lomustine, 90 mg/m\^2
|
Dasatinib, 100 mg/d QD + Lomustine, 90 mg/m^2
n=1 Participants
Dose Level 3B: Dasatinib, 100 mg/d QD plus lomustine, 90 mg/m\^2
|
|---|---|---|---|---|---|
|
Number of Participants With Worst Grade of Hematological Toxicity Per NCI CTCAE Version 3.0 Criteria
At least 1 Grade 1-4 Neutropenia
|
3 participants
|
2 participants
|
2 participants
|
5 participants
|
0 participants
|
|
Number of Participants With Worst Grade of Hematological Toxicity Per NCI CTCAE Version 3.0 Criteria
At least 1 Grade 1-4 Leukopenia
|
5 participants
|
3 participants
|
4 participants
|
6 participants
|
0 participants
|
|
Number of Participants With Worst Grade of Hematological Toxicity Per NCI CTCAE Version 3.0 Criteria
At least 1 Grade 1-4 Lymphocytopenia
|
5 participants
|
2 participants
|
4 participants
|
9 participants
|
0 participants
|
|
Number of Participants With Worst Grade of Hematological Toxicity Per NCI CTCAE Version 3.0 Criteria
At least 1 Grade 1-4 Thrombocytopenia
|
6 participants
|
3 participants
|
6 participants
|
9 participants
|
1 participants
|
|
Number of Participants With Worst Grade of Hematological Toxicity Per NCI CTCAE Version 3.0 Criteria
At least 1 Grade 1-4 Anemia
|
6 participants
|
1 participants
|
6 participants
|
9 participants
|
0 participants
|
|
Number of Participants With Worst Grade of Hematological Toxicity Per NCI CTCAE Version 3.0 Criteria
At least 1 Grade 3-4 Neutropenia
|
2 participants
|
1 participants
|
0 participants
|
4 participants
|
0 participants
|
|
Number of Participants With Worst Grade of Hematological Toxicity Per NCI CTCAE Version 3.0 Criteria
At least 1 Grade 3-4 Leukopenia
|
1 participants
|
1 participants
|
0 participants
|
4 participants
|
0 participants
|
|
Number of Participants With Worst Grade of Hematological Toxicity Per NCI CTCAE Version 3.0 Criteria
At least 1 Grade 3-4 Lymphocytopenia
|
4 participants
|
0 participants
|
1 participants
|
5 participants
|
0 participants
|
|
Number of Participants With Worst Grade of Hematological Toxicity Per NCI CTCAE Version 3.0 Criteria
At least 1 Grade 3-4 Thrombocytopenia
|
4 participants
|
0 participants
|
2 participants
|
5 participants
|
0 participants
|
|
Number of Participants With Worst Grade of Hematological Toxicity Per NCI CTCAE Version 3.0 Criteria
At least 1 Grade 3-4 Anemia
|
0 participants
|
0 participants
|
1 participants
|
0 participants
|
0 participants
|
PRIMARY outcome
Timeframe: 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).Population: Treated participants
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.
Outcome measures
| Measure |
Dasatinib, 100 mg QD/100 mg BID + Lomustine, 110 mg/m^2
n=6 Participants
Dose level 1A. Cycle 1: Dasatinib, 100 mg once daily (QD). Cycle 2: Dasatinib, 100 mg twice daily (BID), plus lomustine, 110 mg/m\^2.
|
Dasatinib, 100 mg QD/100 mg BID + Lomustine, 90 mg/m^2
n=3 Participants
Dose level 1B. Cycle 1: Dasatinib,100 mg QD. Cycle 2: 100 mg BID, plus lomustine, 90 mg/m\^2
|
Dasatinib, 100 mg BID + Lomustine, 90 mg/m^2
n=7 Participants
Dose level 2. Dasatinib, 100 mg BID plus lomustine, 90 mg/m\^2
|
Dasatinib, 150 mg/d + Lomustine, 90 mg/m^2
n=9 Participants
Dose level 3A: Dasatinib, 150 mg/d (100 mg AM and 50 mg PM), plus lomustine, 90 mg/m\^2
|
Dasatinib, 100 mg/d QD + Lomustine, 90 mg/m^2
n=1 Participants
Dose Level 3B: Dasatinib, 100 mg/d QD plus lomustine, 90 mg/m\^2
|
|---|---|---|---|---|---|
|
Number of Participants With Worst Grade of Biochemistry Abnormality Per NCI CTCAE Version 3.0 Criteria
At least 1 Gr 1-4 Creatinine
|
0 participants
|
2 participants
|
0 participants
|
0 participants
|
0 participants
|
|
Number of Participants With Worst Grade of Biochemistry Abnormality Per NCI CTCAE Version 3.0 Criteria
At least 1 Gr 1-4 Aspartate Aminotransferase / AST
|
2 participants
|
0 participants
|
4 participants
|
6 participants
|
0 participants
|
|
Number of Participants With Worst Grade of Biochemistry Abnormality Per NCI CTCAE Version 3.0 Criteria
At least 1 Gr 1-4 Hypokalemia
|
1 participants
|
0 participants
|
1 participants
|
3 participants
|
0 participants
|
|
Number of Participants With Worst Grade of Biochemistry Abnormality Per NCI CTCAE Version 3.0 Criteria
At least 1 Gr 1-4 Hyperkalemia
|
0 participants
|
1 participants
|
0 participants
|
0 participants
|
0 participants
|
|
Number of Participants With Worst Grade of Biochemistry Abnormality Per NCI CTCAE Version 3.0 Criteria
At least 1 Gr 1-4 Hyponatremia
|
1 participants
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
|
Number of Participants With Worst Grade of Biochemistry Abnormality Per NCI CTCAE Version 3.0 Criteria
At least 1 Gr 1-4 Hypernatremia
|
1 participants
|
1 participants
|
0 participants
|
5 participants
|
0 participants
|
|
Number of Participants With Worst Grade of Biochemistry Abnormality Per NCI CTCAE Version 3.0 Criteria
At least 1 Gr 1-4 Hypocalcemia
|
3 participants
|
1 participants
|
3 participants
|
2 participants
|
0 participants
|
|
Number of Participants With Worst Grade of Biochemistry Abnormality Per NCI CTCAE Version 3.0 Criteria
At least 1 Gr1-4 Hyperbilirubinemia
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
1 participants
|
|
Number of Participants With Worst Grade of Biochemistry Abnormality Per NCI CTCAE Version 3.0 Criteria
At least 1 Gr 1-4 Hypophosphatemia
|
1 participants
|
1 participants
|
1 participants
|
3 participants
|
0 participants
|
|
Number of Participants With Worst Grade of Biochemistry Abnormality Per NCI CTCAE Version 3.0 Criteria
At least 1 Gr 3-4 Hypokalemia
|
0 participants
|
0 participants
|
0 participants
|
1 participants
|
0 participants
|
OTHER_PRE_SPECIFIED outcome
Timeframe: 12 monthsPopulation: Treated participants
As measured by brain magnetic resonance imaging.
Outcome measures
| Measure |
Dasatinib, 100 mg QD/100 mg BID + Lomustine, 110 mg/m^2
n=6 Participants
Dose level 1A. Cycle 1: Dasatinib, 100 mg once daily (QD). Cycle 2: Dasatinib, 100 mg twice daily (BID), plus lomustine, 110 mg/m\^2.
|
Dasatinib, 100 mg QD/100 mg BID + Lomustine, 90 mg/m^2
n=3 Participants
Dose level 1B. Cycle 1: Dasatinib,100 mg QD. Cycle 2: 100 mg BID, plus lomustine, 90 mg/m\^2
|
Dasatinib, 100 mg BID + Lomustine, 90 mg/m^2
n=7 Participants
Dose level 2. Dasatinib, 100 mg BID plus lomustine, 90 mg/m\^2
|
Dasatinib, 150 mg/d + Lomustine, 90 mg/m^2
n=9 Participants
Dose level 3A: Dasatinib, 150 mg/d (100 mg AM and 50 mg PM), plus lomustine, 90 mg/m\^2
|
Dasatinib, 100 mg/d QD + Lomustine, 90 mg/m^2
n=1 Participants
Dose Level 3B: Dasatinib, 100 mg/d QD plus lomustine, 90 mg/m\^2
|
|---|---|---|---|---|---|
|
Number of Participants With Disease Progression at 12 Months
|
6 participants
|
3 participants
|
7 participants
|
9 participants
|
1 participants
|
Adverse Events
Dasatinib, 100 mg QD/100 mg BID + Lomustine, 110 mg/m^2
Serious events: 5 serious events
Other events: 6 other events
Deaths: 0 deaths
Dasatinib, 100 mg QD/100 mg BID + Lomustine, 90 mg/m^2
Serious events: 1 serious events
Other events: 3 other events
Deaths: 0 deaths
Dasatinib, 100 mg BID + Lomustine, 90 mg/m^2
Serious events: 4 serious events
Other events: 7 other events
Deaths: 0 deaths
Dasatinib, 150 mg/d + Lomustine, 90 mg/m^2
Serious events: 3 serious events
Other events: 9 other events
Deaths: 0 deaths
Dasatinib, 100 mg/d QD + Lomustine, 90 mg/m^2
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Dasatinib, 100 mg QD/100 mg BID + Lomustine, 110 mg/m^2
n=6 participants at risk
Dose level 1A. Cycle 1: Dasatinib, 100 mg once daily (QD). Cycle 2: Dasatinib, 100 mg twice daily (BID), plus lomustine, 110 mg/m\^2.
|
Dasatinib, 100 mg QD/100 mg BID + Lomustine, 90 mg/m^2
n=3 participants at risk
Dose level 1B. Cycle 1: Dasatinib,100 mg QD. Cycle 2: 100 mg BID, plus lomustine, 90 mg/m\^2
|
Dasatinib, 100 mg BID + Lomustine, 90 mg/m^2
n=7 participants at risk
Dose level 2. Dasatinib, 100 mg BID plus lomustine, 90 mg/m\^2
|
Dasatinib, 150 mg/d + Lomustine, 90 mg/m^2
n=9 participants at risk
Dose level 3A: Dasatinib, 150 mg/d (100 mg AM and 50 mg PM), plus lomustine, 90 mg/m\^2
|
Dasatinib, 100 mg/d QD + Lomustine, 90 mg/m^2
n=1 participants at risk
Dose Level 3B: Dasatinib, 100 mg/d QD plus lomustine, 90 mg/m\^2
|
|---|---|---|---|---|---|
|
Metabolism and nutrition disorders
Decreased appetite
|
0.00%
0/6
|
0.00%
0/3
|
14.3%
1/7
|
0.00%
0/9
|
0.00%
0/1
|
|
Nervous system disorders
Convulsion
|
0.00%
0/6
|
33.3%
1/3
|
14.3%
1/7
|
22.2%
2/9
|
0.00%
0/1
|
|
Investigations
Neutrophil count decreased
|
0.00%
0/6
|
0.00%
0/3
|
0.00%
0/7
|
22.2%
2/9
|
0.00%
0/1
|
|
Blood and lymphatic system disorders
Anaemia
|
0.00%
0/6
|
0.00%
0/3
|
14.3%
1/7
|
0.00%
0/9
|
0.00%
0/1
|
|
Nervous system disorders
Headache
|
0.00%
0/6
|
0.00%
0/3
|
0.00%
0/7
|
11.1%
1/9
|
0.00%
0/1
|
|
Gastrointestinal disorders
Enteritis
|
0.00%
0/6
|
33.3%
1/3
|
0.00%
0/7
|
0.00%
0/9
|
0.00%
0/1
|
|
General disorders
Pyrexia
|
0.00%
0/6
|
0.00%
0/3
|
0.00%
0/7
|
11.1%
1/9
|
0.00%
0/1
|
|
Injury, poisoning and procedural complications
Subdural haematoma
|
16.7%
1/6
|
0.00%
0/3
|
0.00%
0/7
|
0.00%
0/9
|
0.00%
0/1
|
|
General disorders
Death
|
16.7%
1/6
|
0.00%
0/3
|
14.3%
1/7
|
0.00%
0/9
|
0.00%
0/1
|
|
Infections and infestations
Urosepsis
|
0.00%
0/6
|
0.00%
0/3
|
14.3%
1/7
|
0.00%
0/9
|
0.00%
0/1
|
|
Nervous system disorders
Brain oedema
|
0.00%
0/6
|
0.00%
0/3
|
14.3%
1/7
|
0.00%
0/9
|
0.00%
0/1
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
0.00%
0/6
|
0.00%
0/3
|
0.00%
0/7
|
11.1%
1/9
|
0.00%
0/1
|
|
Investigations
Platelet count decreased
|
33.3%
2/6
|
0.00%
0/3
|
0.00%
0/7
|
0.00%
0/9
|
0.00%
0/1
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
16.7%
1/6
|
0.00%
0/3
|
0.00%
0/7
|
0.00%
0/9
|
0.00%
0/1
|
Other adverse events
| Measure |
Dasatinib, 100 mg QD/100 mg BID + Lomustine, 110 mg/m^2
n=6 participants at risk
Dose level 1A. Cycle 1: Dasatinib, 100 mg once daily (QD). Cycle 2: Dasatinib, 100 mg twice daily (BID), plus lomustine, 110 mg/m\^2.
|
Dasatinib, 100 mg QD/100 mg BID + Lomustine, 90 mg/m^2
n=3 participants at risk
Dose level 1B. Cycle 1: Dasatinib,100 mg QD. Cycle 2: 100 mg BID, plus lomustine, 90 mg/m\^2
|
Dasatinib, 100 mg BID + Lomustine, 90 mg/m^2
n=7 participants at risk
Dose level 2. Dasatinib, 100 mg BID plus lomustine, 90 mg/m\^2
|
Dasatinib, 150 mg/d + Lomustine, 90 mg/m^2
n=9 participants at risk
Dose level 3A: Dasatinib, 150 mg/d (100 mg AM and 50 mg PM), plus lomustine, 90 mg/m\^2
|
Dasatinib, 100 mg/d QD + Lomustine, 90 mg/m^2
n=1 participants at risk
Dose Level 3B: Dasatinib, 100 mg/d QD plus lomustine, 90 mg/m\^2
|
|---|---|---|---|---|---|
|
Psychiatric disorders
Agitation
|
16.7%
1/6
|
33.3%
1/3
|
0.00%
0/7
|
0.00%
0/9
|
0.00%
0/1
|
|
Psychiatric disorders
Anxiety
|
0.00%
0/6
|
0.00%
0/3
|
0.00%
0/7
|
11.1%
1/9
|
0.00%
0/1
|
|
Metabolism and nutrition disorders
Decreased appetite
|
16.7%
1/6
|
33.3%
1/3
|
14.3%
1/7
|
11.1%
1/9
|
0.00%
0/1
|
|
Nervous system disorders
Dysgeusia
|
0.00%
0/6
|
33.3%
1/3
|
0.00%
0/7
|
11.1%
1/9
|
0.00%
0/1
|
|
Gastrointestinal disorders
Dyspepsia
|
0.00%
0/6
|
33.3%
1/3
|
0.00%
0/7
|
0.00%
0/9
|
0.00%
0/1
|
|
Immune system disorders
Hypersensitivity
|
16.7%
1/6
|
0.00%
0/3
|
0.00%
0/7
|
0.00%
0/9
|
0.00%
0/1
|
|
Reproductive system and breast disorders
Prostatism
|
0.00%
0/6
|
33.3%
1/3
|
0.00%
0/7
|
0.00%
0/9
|
0.00%
0/1
|
|
Nervous system disorders
Somnolence
|
16.7%
1/6
|
0.00%
0/3
|
0.00%
0/7
|
0.00%
0/9
|
0.00%
0/1
|
|
Nervous system disorders
Speech disorder
|
16.7%
1/6
|
66.7%
2/3
|
14.3%
1/7
|
11.1%
1/9
|
0.00%
0/1
|
|
Renal and urinary disorders
Urinary retention
|
0.00%
0/6
|
0.00%
0/3
|
14.3%
1/7
|
0.00%
0/9
|
0.00%
0/1
|
|
Eye disorders
Vision blurred
|
0.00%
0/6
|
0.00%
0/3
|
14.3%
1/7
|
0.00%
0/9
|
0.00%
0/1
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
16.7%
1/6
|
66.7%
2/3
|
14.3%
1/7
|
11.1%
1/9
|
0.00%
0/1
|
|
Investigations
Carbon monoxide diffusing capacity
|
0.00%
0/6
|
66.7%
2/3
|
42.9%
3/7
|
33.3%
3/9
|
100.0%
1/1
|
|
Nervous system disorders
Convulsion
|
0.00%
0/6
|
33.3%
1/3
|
0.00%
0/7
|
11.1%
1/9
|
0.00%
0/1
|
|
Infections and infestations
Cystitis
|
0.00%
0/6
|
0.00%
0/3
|
14.3%
1/7
|
0.00%
0/9
|
0.00%
0/1
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
50.0%
3/6
|
33.3%
1/3
|
14.3%
1/7
|
0.00%
0/9
|
0.00%
0/1
|
|
Investigations
Neutrophil count decreased
|
0.00%
0/6
|
0.00%
0/3
|
0.00%
0/7
|
11.1%
1/9
|
0.00%
0/1
|
|
Eye disorders
Ocular surface disease
|
0.00%
0/6
|
0.00%
0/3
|
14.3%
1/7
|
0.00%
0/9
|
0.00%
0/1
|
|
Nervous system disorders
Peripheral motor neuropathy
|
66.7%
4/6
|
33.3%
1/3
|
42.9%
3/7
|
55.6%
5/9
|
0.00%
0/1
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
0.00%
0/6
|
0.00%
0/3
|
14.3%
1/7
|
0.00%
0/9
|
0.00%
0/1
|
|
Cardiac disorders
Conduction disorder
|
16.7%
1/6
|
0.00%
0/3
|
0.00%
0/7
|
0.00%
0/9
|
0.00%
0/1
|
|
Psychiatric disorders
Confusional state
|
16.7%
1/6
|
0.00%
0/3
|
14.3%
1/7
|
22.2%
2/9
|
0.00%
0/1
|
|
Vascular disorders
Deep vein thrombosis
|
0.00%
0/6
|
0.00%
0/3
|
14.3%
1/7
|
0.00%
0/9
|
0.00%
0/1
|
|
Nervous system disorders
Hemianopia homonymous
|
0.00%
0/6
|
33.3%
1/3
|
0.00%
0/7
|
0.00%
0/9
|
0.00%
0/1
|
|
Gastrointestinal disorders
Nausea
|
66.7%
4/6
|
33.3%
1/3
|
57.1%
4/7
|
66.7%
6/9
|
0.00%
0/1
|
|
Vascular disorders
Peripheral coldness
|
16.7%
1/6
|
0.00%
0/3
|
0.00%
0/7
|
0.00%
0/9
|
0.00%
0/1
|
|
Nervous system disorders
Peripheral sensory neuropathy
|
33.3%
2/6
|
66.7%
2/3
|
28.6%
2/7
|
11.1%
1/9
|
0.00%
0/1
|
|
Renal and urinary disorders
Urethral haemorrhage
|
0.00%
0/6
|
0.00%
0/3
|
14.3%
1/7
|
0.00%
0/9
|
0.00%
0/1
|
|
Investigations
Weight increased
|
16.7%
1/6
|
0.00%
0/3
|
0.00%
0/7
|
0.00%
0/9
|
0.00%
0/1
|
|
Gastrointestinal disorders
Abdominal pain
|
0.00%
0/6
|
0.00%
0/3
|
14.3%
1/7
|
0.00%
0/9
|
0.00%
0/1
|
|
Blood and lymphatic system disorders
Anaemia
|
0.00%
0/6
|
0.00%
0/3
|
14.3%
1/7
|
0.00%
0/9
|
0.00%
0/1
|
|
Eye disorders
Dry eye
|
16.7%
1/6
|
0.00%
0/3
|
0.00%
0/7
|
0.00%
0/9
|
0.00%
0/1
|
|
Nervous system disorders
Headache
|
50.0%
3/6
|
33.3%
1/3
|
57.1%
4/7
|
33.3%
3/9
|
100.0%
1/1
|
|
Nervous system disorders
Memory impairment
|
0.00%
0/6
|
33.3%
1/3
|
14.3%
1/7
|
0.00%
0/9
|
0.00%
0/1
|
|
Cardiac disorders
Sinus bradycardia
|
0.00%
0/6
|
0.00%
0/3
|
0.00%
0/7
|
11.1%
1/9
|
0.00%
0/1
|
|
Infections and infestations
Skin infection
|
0.00%
0/6
|
0.00%
0/3
|
14.3%
1/7
|
0.00%
0/9
|
0.00%
0/1
|
|
Ear and labyrinth disorders
Tinnitus
|
0.00%
0/6
|
33.3%
1/3
|
0.00%
0/7
|
0.00%
0/9
|
0.00%
0/1
|
|
General disorders
Adverse event
|
0.00%
0/6
|
0.00%
0/3
|
14.3%
1/7
|
0.00%
0/9
|
0.00%
0/1
|
|
Cardiac disorders
Angina pectoris
|
16.7%
1/6
|
0.00%
0/3
|
0.00%
0/7
|
0.00%
0/9
|
0.00%
0/1
|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/6
|
33.3%
1/3
|
14.3%
1/7
|
0.00%
0/9
|
0.00%
0/1
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
16.7%
1/6
|
0.00%
0/3
|
0.00%
0/7
|
11.1%
1/9
|
0.00%
0/1
|
|
General disorders
Fatigue
|
100.0%
6/6
|
100.0%
3/3
|
85.7%
6/7
|
66.7%
6/9
|
100.0%
1/1
|
|
Renal and urinary disorders
Pollakiuria
|
50.0%
3/6
|
0.00%
0/3
|
0.00%
0/7
|
11.1%
1/9
|
0.00%
0/1
|
|
General disorders
Pyrexia
|
16.7%
1/6
|
0.00%
0/3
|
14.3%
1/7
|
0.00%
0/9
|
0.00%
0/1
|
|
Gastrointestinal disorders
Vomiting
|
66.7%
4/6
|
0.00%
0/3
|
42.9%
3/7
|
55.6%
5/9
|
100.0%
1/1
|
|
Investigations
Weight decreased
|
16.7%
1/6
|
33.3%
1/3
|
0.00%
0/7
|
0.00%
0/9
|
0.00%
0/1
|
|
Nervous system disorders
Ataxia
|
0.00%
0/6
|
0.00%
0/3
|
14.3%
1/7
|
0.00%
0/9
|
0.00%
0/1
|
|
Nervous system disorders
Cognitive disorder
|
0.00%
0/6
|
0.00%
0/3
|
0.00%
0/7
|
11.1%
1/9
|
0.00%
0/1
|
|
Gastrointestinal disorders
Dry mouth
|
0.00%
0/6
|
33.3%
1/3
|
0.00%
0/7
|
0.00%
0/9
|
0.00%
0/1
|
|
Nervous system disorders
Hemianopia
|
0.00%
0/6
|
0.00%
0/3
|
0.00%
0/7
|
22.2%
2/9
|
0.00%
0/1
|
|
General disorders
Oedema peripheral
|
16.7%
1/6
|
0.00%
0/3
|
0.00%
0/7
|
0.00%
0/9
|
0.00%
0/1
|
|
Eye disorders
Optic neuropathy
|
33.3%
2/6
|
0.00%
0/3
|
0.00%
0/7
|
0.00%
0/9
|
0.00%
0/1
|
|
Infections and infestations
Urosepsis
|
0.00%
0/6
|
0.00%
0/3
|
14.3%
1/7
|
0.00%
0/9
|
0.00%
0/1
|
|
Nervous system disorders
Brain oedema
|
0.00%
0/6
|
0.00%
0/3
|
14.3%
1/7
|
0.00%
0/9
|
0.00%
0/1
|
|
Psychiatric disorders
Depressed mood
|
0.00%
0/6
|
66.7%
2/3
|
0.00%
0/7
|
11.1%
1/9
|
0.00%
0/1
|
|
Gastrointestinal disorders
Diarrhoea
|
16.7%
1/6
|
0.00%
0/3
|
57.1%
4/7
|
33.3%
3/9
|
0.00%
0/1
|
|
General disorders
Face oedema
|
16.7%
1/6
|
0.00%
0/3
|
0.00%
0/7
|
0.00%
0/9
|
0.00%
0/1
|
|
Nervous system disorders
Hyperaesthesia
|
16.7%
1/6
|
0.00%
0/3
|
0.00%
0/7
|
0.00%
0/9
|
0.00%
0/1
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
33.3%
2/6
|
33.3%
1/3
|
0.00%
0/7
|
11.1%
1/9
|
0.00%
0/1
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal stiffness
|
0.00%
0/6
|
0.00%
0/3
|
14.3%
1/7
|
0.00%
0/9
|
0.00%
0/1
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasm swelling
|
16.7%
1/6
|
0.00%
0/3
|
0.00%
0/7
|
0.00%
0/9
|
0.00%
0/1
|
|
Investigations
Platelet count decreased
|
50.0%
3/6
|
0.00%
0/3
|
0.00%
0/7
|
11.1%
1/9
|
0.00%
0/1
|
|
Infections and infestations
Urinary tract infection
|
0.00%
0/6
|
33.3%
1/3
|
14.3%
1/7
|
0.00%
0/9
|
0.00%
0/1
|
|
Musculoskeletal and connective tissue disorders
Arthropathy
|
0.00%
0/6
|
0.00%
0/3
|
14.3%
1/7
|
0.00%
0/9
|
0.00%
0/1
|
|
Nervous system disorders
Dizziness
|
16.7%
1/6
|
33.3%
1/3
|
14.3%
1/7
|
22.2%
2/9
|
0.00%
0/1
|
|
Skin and subcutaneous tissue disorders
Exfoliative rash
|
16.7%
1/6
|
33.3%
1/3
|
0.00%
0/7
|
11.1%
1/9
|
100.0%
1/1
|
|
Gastrointestinal disorders
Haemorrhoids
|
0.00%
0/6
|
0.00%
0/3
|
14.3%
1/7
|
0.00%
0/9
|
0.00%
0/1
|
|
Infections and infestations
Lung infection
|
0.00%
0/6
|
0.00%
0/3
|
0.00%
0/7
|
11.1%
1/9
|
0.00%
0/1
|
|
Skin and subcutaneous tissue disorders
Nail disorder
|
16.7%
1/6
|
0.00%
0/3
|
0.00%
0/7
|
0.00%
0/9
|
0.00%
0/1
|
|
Skin and subcutaneous tissue disorders
Penile ulceration
|
0.00%
0/6
|
0.00%
0/3
|
14.3%
1/7
|
0.00%
0/9
|
0.00%
0/1
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
16.7%
1/6
|
0.00%
0/3
|
0.00%
0/7
|
0.00%
0/9
|
0.00%
0/1
|
|
Gastrointestinal disorders
Stomatitis
|
33.3%
2/6
|
0.00%
0/3
|
0.00%
0/7
|
0.00%
0/9
|
0.00%
0/1
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication.
- Publication restrictions are in place
Restriction type: OTHER