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Phase II Study of BKM120 for Subjects With Recurrent Glioblastoma

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.
ClinicalTrials.gov Identifier: NCT01339052
Recruitment Status : Completed
First Posted : April 20, 2011
Results First Posted : June 14, 2017
Last Update Posted : March 19, 2019
Sponsor:
Collaborators:
Brigham and Women's Hospital
Massachusetts General Hospital
Novartis Pharmaceuticals
M.D. Anderson Cancer Center
Memorial Sloan Kettering Cancer Center
University of California, San Francisco
University of California, Los Angeles
University of Utah
Information provided by (Responsible Party):
Patrick Y. Wen, MD, Dana-Farber/Brigham and Women's Cancer Center

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Glioblastoma
Interventions Drug: BKM120
Procedure: Surgery
Enrollment 65
Recruitment Details Patients enrolled from September 2011 through February 2014.
Pre-assignment Details  
Arm/Group Title Cohort 1: Surgical Subjects Cohort 2: Non-surgical Subjects
Hide Arm/Group Description

Subjects scheduled for surgery

BKM120: 100 mg once daily, orally, for 8-12 days prior to surgery

Surgery: Surgery

BKM120: 100 mg once daily, orally, for 28-day cycles

Participants continued treatment until disease progression or unacceptable toxicity.

Subjects not candidates for surgery

BKM120: 100 mg once daily, orally, for 28-day cycles

Participants continued treatment until disease progression or unacceptable toxicity.

Period Title: Overall Study
Started 15 50
Measurable Disease [1] 11 40 [2]
Evaluable Tumor Sample at Surgery 14 0 [3]
Evaluable Plasma Sample at Surgery 13 0 [3]
Completed [4] 0 0
Not Completed 15 50
Reason Not Completed
Disease progression             13             46
Adverse Event             1             1
Withdrawal by Subject             0             3
Physician Decision             1             0
[1]
Measurable disease post-surgery for Cohort 1 participants.
[2]
Radiographic response evaluated on participants with measurable disease only.
[3]
Milestone is not relevant for non-surgical cohort.
[4]
Since treatment was not of fixed duration, all participants were considered as 'Not Completed'.
Arm/Group Title Cohort 1: Surgical Subjects Cohort 2: Non-surgical Subjects Total
Hide Arm/Group Description

Subjects scheduled for surgery

BKM120: 100 mg once daily, orally, for 8-12 days prior to surgery

Surgery: Surgery

BKM120: 100 mg once daily, orally, for 28-day cycles

Participants continued treatment until disease progression or unacceptable toxicity.

Subjects not candidates for surgery

BKM120: 100 mg once daily, orally, for 28-day cycles

Participants continued treatment until disease progression or unacceptable toxicity.

Total of all reporting groups
Overall Number of Baseline Participants 15 50 65
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 15 participants 50 participants 65 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
13
  86.7%
43
  86.0%
56
  86.2%
>=65 years
2
  13.3%
7
  14.0%
9
  13.8%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 15 participants 50 participants 65 participants
Female
4
  26.7%
13
  26.0%
17
  26.2%
Male
11
  73.3%
37
  74.0%
48
  73.8%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 15 participants 50 participants 65 participants
Hispanic or Latino
0
   0.0%
2
   4.0%
2
   3.1%
Not Hispanic or Latino
11
  73.3%
35
  70.0%
46
  70.8%
Unknown or Not Reported
4
  26.7%
13
  26.0%
17
  26.2%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 15 participants 50 participants 65 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
0
   0.0%
3
   6.0%
3
   4.6%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
0
   0.0%
0
   0.0%
0
   0.0%
White
12
  80.0%
32
  64.0%
44
  67.7%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
3
  20.0%
15
  30.0%
18
  27.7%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
United States Number Analyzed 15 participants 50 participants 65 participants
15
 100.0%
50
 100.0%
65
 100.0%
Karnofsky performance status (KPS)   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 15 participants 50 participants 65 participants
70
1
   6.7%
3
   6.0%
4
   6.2%
80
2
  13.3%
15
  30.0%
17
  26.2%
90
10
  66.7%
23
  46.0%
33
  50.8%
100
2
  13.3%
9
  18.0%
11
  16.9%
[1]
Measure Description: 'Karnofsky Performance Status' (KPS) scale: 100 = Normal; no complaints; no evidence of disease; 90 = Able to carry on normal activity; minor signs or symptoms of disease; 80 = Normal activity with effort; some sign or symptoms of disease; 70 = Cares for self; unable to carry on normal activity or do active work.
Current Tumor Diagnosis  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 15 participants 50 participants 65 participants
Glioblstoma Multiforme (GBM)
15
 100.0%
47
  94.0%
62
  95.4%
Gliosarcoma
0
   0.0%
3
   6.0%
3
   4.6%
Initial Tumor Diagnosis  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 15 participants 50 participants 65 participants
Glioblastoma Multiforme (GBM)
13
  86.7%
41
  82.0%
54
  83.1%
Anaplastic Astrocytoma (AA) merging w Glioblastoma
1
   6.7%
0
   0.0%
1
   1.5%
Gr4 Right Parietal Glioma
1
   6.7%
0
   0.0%
1
   1.5%
Astrocytoma
0
   0.0%
1
   2.0%
1
   1.5%
Anaplastic Astrocytoma (AA)
0
   0.0%
3
   6.0%
3
   4.6%
Gemistocytic Astrocyoma
0
   0.0%
1
   2.0%
1
   1.5%
Glioma consistent w/ mixed Oligoastrocytoma
0
   0.0%
1
   2.0%
1
   1.5%
Gliosarcoma
0
   0.0%
1
   2.0%
1
   1.5%
High grade astrocytoma/glioblastoma
0
   0.0%
1
   2.0%
1
   1.5%
Oligodendroglioma
0
   0.0%
1
   2.0%
1
   1.5%
PTEN Status at Registration via Central Path Review  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 15 participants 50 participants 65 participants
PTEN Negative
7
  46.7%
34
  68.0%
41
  63.1%
Not PTEN Negative
8
  53.3%
12
  24.0%
20
  30.8%
PTEN loss by FISH
0
   0.0%
1
   2.0%
1
   1.5%
PTEN Mutant
0
   0.0%
1
   2.0%
1
   1.5%
Unknown/Pending
0
   0.0%
2
   4.0%
2
   3.1%
pAKT StatusStatus at Registration via Central Path Review  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 15 participants 50 participants 65 participants
pAKT Positive
15
 100.0%
39
  78.0%
54
  83.1%
pAKT Negative
0
   0.0%
2
   4.0%
2
   3.1%
Unknown/Pending
0
   0.0%
9
  18.0%
9
  13.8%
Mutation Status at Registration  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 15 participants 50 participants 65 participants
PIK3CA mutation
1
   6.7%
2
   4.0%
3
   4.6%
Negative
0
   0.0%
1
   2.0%
1
   1.5%
Unknown/Pending
14
  93.3%
47
  94.0%
61
  93.8%
1.Primary Outcome
Title Change in pAKT (S473) Immunohistochemistry (IHC) Score From Baseline to Surgery [Cohort 1]
Hide Description pAKT response was determined by pathologist-performed semi-quantitative IHC scoring for pAKT using previously established methods for glioblastoma (GBM) patients. Sample staining scored for intensity on a 0-2+ scale (0 none, 1+ weak positive, 2+ strong positive). Change in pAKT IHC score was the difference in score from baseline to surgery. Participants were classified into 3 groups: a reduction of staining score of one degree or more (considered a response), an increase in score and no change in score.
Time Frame Samples were collected at baseline and at surgery (resected surgical tumor specimen) which occurred after up to 12 days of BKM120 treatment.
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis dataset is comprised of all treated participants.
Arm/Group Title Cohort 1: Surgical Subjects
Hide Arm/Group Description:

Subjects scheduled for surgery

BKM120: 100 mg once daily, orally, for 8-12 days prior to surgery

Surgery: Surgery

BKM120: 100 mg once daily, orally, for 28-day cycles

Participants continued treatment until disease progression or unacceptable toxicity.

Overall Number of Participants Analyzed 15
Measure Type: Count of Participants
Unit of Measure: Participants
reduced pAKT (S473) IHC Score
6
  40.0%
increased pAKT (S473) IHC Score
1
   6.7%
no change in pAKT (S473) IHC Score
7
  46.7%
Unevaluable
1
   6.7%
2.Primary Outcome
Title 6-Month Progression-Free Survival (PFS6) [Cohort 2]
Hide Description PFS6 is the proportion of participants remaining alive and progression-free at 6-months from cycle 1 day 1 of BKM120 treatment. Progressive disease is defined using RANO (Response Assessment in Neuro-Oncology) criteria (Wen et al JCO 2010), which takes modified Macdonald Criteria and adds assessment of non-enhancing lesions. Per RANO, progressive disease (PD) is defined either as > 25% increase in sum of the products of perpendicular diameters of enhancing lesions on stable or increasing doses of corticosteroids, or one or more of the of the following: 1) Significant increase in T2/FLAIR non-enhancing lesion on stable or increasing doses of corticosteroids steroids not due to co-morbid events; 2) Any new lesion; 3) Clear clinical deterioration not attributable to other causes apart from the tumor; or 4) Failure to return for evaluation due to death or deteriorating condition.
Time Frame Participants were assessed radiologically every other cycle on treatment; Relevant for this outcome is up to month 6 evaluation.
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis dataset is comprised of all treated participants.
Arm/Group Title Cohort 2: Non-surgical Subjects
Hide Arm/Group Description:

Subjects not candidates for surgery

BKM120: 100 mg once daily, orally, for 28-day cycles

Participants continued treatment until disease progression or unacceptable toxicity.

Overall Number of Participants Analyzed 50
Measure Type: Number
Number (90% Confidence Interval)
Unit of Measure: proportion of participants
0.08
(0.028 to 0.174)
3.Primary Outcome
Title BKM120 Brain-to-Plasma Ratio at Time of Surgery [Cohort 1]
Hide Description Levels of BKM120 were determined by liquid chromatography coupled with tandem mass spectrometry. BKM120 tumor-to-plasma ratio at time of surgery was calculated based on these levels.
Time Frame Samples were collected at surgery (surgical tumor specimen and plasma sample) which occurred after up to 12 days of BKM120 treatment.
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis dataset is comprised of participants with a paired plasma and brain tumor sample (evaluable). Participants missing a brain tumor sample (n=1) or plasma sample (n=2) are excluded from the calculation.
Arm/Group Title Cohort 1: Surgical Subjects
Hide Arm/Group Description:

Subjects scheduled for surgery

BKM120: 100 mg once daily, orally, for 8-12 days prior to surgery

Surgery: Surgery

BKM120: 100 mg once daily, orally, for 28-day cycles

Participants continued treatment until disease progression or unacceptable toxicity.

Overall Number of Participants Analyzed 13
Geometric Mean (Full Range)
Unit of Measure: ratio tumor-to-plasma
1.00
(0.18 to 8.44)
4.Primary Outcome
Title BKM120 Tumor Tissue Concentration at Time of Surgery [Cohort 1]
Hide Description Levels of BKM120 were determined by liquid chromatography coupled with tandem mass spectrometry.
Time Frame Samples were collected at surgery (resected surgical tumor specimen) which occurred after up to 12 days of BKM120 treatment.
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis dataset is comprised of all participants with a resected surgical tumor specimen (evaluable).
Arm/Group Title Cohort 1: Surgical Subjects
Hide Arm/Group Description:

Subjects scheduled for surgery

BKM120: 100 mg once daily, orally, for 8-12 days prior to surgery

Surgery: Surgery

BKM120: 100 mg once daily, orally, for 28-day cycles

Participants continued treatment until disease progression or unacceptable toxicity.

Overall Number of Participants Analyzed 14
Geometric Mean (Full Range)
Unit of Measure: ng/gm
590
(86 to 6947)
5.Primary Outcome
Title BKM120 Plasma Concentration at Time of Surgery [Cohort 1]
Hide Description Levels of BKM120 were determined by liquid chromatography coupled with tandem mass spectrometry.
Time Frame Samples were collected at surgery which occurred after up to 12 days of BKM120 treatment.
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis dataset is comprised of all participants with a plasma sample at surgery (evaluable).
Arm/Group Title Cohort 1: Surgical Subjects
Hide Arm/Group Description:

Subjects scheduled for surgery

BKM120: 100 mg once daily, orally, for 8-12 days prior to surgery

Surgery: Surgery

BKM120: 100 mg once daily, orally, for 28-day cycles

Participants continued treatment until disease progression or unacceptable toxicity.

Overall Number of Participants Analyzed 13
Mean (Standard Deviation)
Unit of Measure: ng/mL
585  (192)
6.Secondary Outcome
Title % Ki-67 Reduction Using Immunohistochemistry (IHC) [Cohort 1]
Hide Description Tumor cell proliferation and tumor cell death was using immunohistochemistry for Ki-67 based on established methods. Percent reduction was based on Ki-67 levels at baseline and at surgery.
Time Frame Samples were collected at baseline (archival tumor specimen) and at surgery (surgical tumor specimen) which occurred after up to 12 days of BTK120 treatment.
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis dataset is comprised of all participants with a resected surgical tumor specimen (evaluable).
Arm/Group Title Cohort I: Surgical Subjects
Hide Arm/Group Description:

Subjects scheduled for surgery

BKM120: 100 mg once daily, orally, for 8-12 days prior to surgery

Surgery: Surgery

BKM120: 100 mg once daily, orally, for 28-day cycles

Participants continued treatment until disease progression or unacceptable toxicity.

Overall Number of Participants Analyzed 14
Median (Full Range)
Unit of Measure: % reduction
11
(-81 to 100)
7.Secondary Outcome
Title Radiographic Response [Cohort 2]
Hide Description Radiographic response was based on RANO (Response Assessment in Neuro-Oncology) criteria. Per RANO, complete response (CR): 1) Complete disappearance of all enhancing measurable and non-measurable disease sustained for at least 4 weeks, 2) No new lesions, 3) All lesions assessed using the same techniques as baseline, 4) No steroid use (or on physiologic replacement doses only), 5) Stable or improved non-enhancing (T2/FLAIR) lesions and 6) Stable or improved clinically; partial response (PR): 1) >/= 50% decrease compared to baseline in the sum of products of perpendicular diameters of all measurable enhancing lesions (sum LD) sustained for at least 4 weeks and 2) No progression; progressive disease (PD): 1) > 25% increase sum LD and/or 2) significant increase in T2/FLAIR, 3) any new lesion, 4) clear clinical deterioration; stable disease (SD): none of the above.
Time Frame Participants were assessed radiologically every other cycle on treatment. Cohort 2 participants were on treatment up to 9.2 months.
Hide Outcome Measure Data
Hide Analysis Population Description
Only those participants who had measurable disease present at baseline and received at least one dose of therapy are considered evaluable for radiographic response
Arm/Group Title Cohort 2: Non-surgical Subjects
Hide Arm/Group Description:

Subjects not candidates for surgery

BKM120: 100 mg once daily, orally, for 28-day cycles

Participants continued treatment until disease progression or unacceptable toxicity.

Overall Number of Participants Analyzed 40
Measure Type: Count of Participants
Unit of Measure: Participants
Stable Disease
16
  40.0%
Progressive Disease
22
  55.0%
Not Evaluable
2
   5.0%
8.Secondary Outcome
Title Maximum Observed Plasma Concentrations (Cmax) of BKM120 Day 1 and Day 8 [Cohort 1]
Hide Description

Plasma concentrations of BKM120 were analyzed by a validated liquid chromatography-tandem mass spectrometry assay developed by Novartis Pharma AG. Standard Pk parameters were determined using non-compartmental methods.

NOTE: This outcome measure was previously titled: "Investigate Pharmacokinetics of BKM120 in This Population by Comparing Maximum Plasma Concentrations (Cmax) From Day 1 to Day 8”

Time Frame On days 1 and 8 (+/- 1 day) prior to surgery, 5 blood samples were collected at the following timepoints: pre-dose, and at 0.5, 1.5, 3, and 5 hours post-dose.
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis dataset is comprised of all treated patients.
Arm/Group Title Cohort 1: Surgical Subjects
Hide Arm/Group Description:

Subjects scheduled for surgery

BKM120: 100 mg once daily, orally, for 8-12 days prior to surgery

Surgery: Surgery

BKM120: 100 mg once daily, orally, for 28-day cycles

Participants continued treatment until disease progression or unacceptable toxicity.

Overall Number of Participants Analyzed 15
Mean (Standard Deviation)
Unit of Measure: ng/mL
Day 1 471  (147)
Day 8 820  (192)
9.Secondary Outcome
Title Cmax Accumulation Ratio of BKM120 Day 1 and Day 8 Ratio [Cohort 1]
Hide Description Plasma concentrations of BKM120 were analyzed by a validated liquid chromatography-tandem mass spectrometry assay developed by Novartis Pharma AG. Standard Pk parameters were determined using non-compartmental methods. The accumulation ratio is day 8/day 1.
Time Frame On days 1 and 8 (+/- 1 day) prior to surgery, 5 blood samples were collected at the following timepoints: pre-dose, and at 0.5, 1.5, 3, and 5 hours post-dose.
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis dataset is comprised of all treated patients.
Arm/Group Title Cohort I: Surgical Subjects
Hide Arm/Group Description:

Subjects scheduled for surgery

BKM120: 100 mg once daily, orally, for 8-12 days prior to surgery

Surgery: Surgery

BKM120: 100 mg once daily, orally, for 28-day cycles

Participants continued treatment until disease progression or unacceptable toxicity.

Overall Number of Participants Analyzed 15
Mean (Full Range)
Unit of Measure: ratio day 8/day 1
1.88
(1.377 to 2.383)
10.Secondary Outcome
Title Area Under the Concentration Curve From Time 0 to Last Concentration (AUC0-5h) of BKM120 Day 1 and Day 8 [Cohort 1]
Hide Description

Plasma concentrations of BKM120 were analyzed by a validated liquid chromatography-tandem mass spectrometry assay developed by Novartis Pharma AG. Standard Pk parameters were determined using non-compartmental methods.

NOTE: This outcome measure was previously titled: "Investigate Pharmacokinetics of BKM120 in This Population by Comparing the Drug Exposure Area Under the Curve (AUC0-5h) From Day 1 to Day 8”

Time Frame On days 1 and 8 (+/- 1 day) prior to surgery, 5 blood samples were collected at the following timepoints: pre-dose, and at 0.5, 1.5, 3, and 5 hours post-dose.
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis dataset is comprised of all treated patients.
Arm/Group Title Cohort 1: Surgical Subjects
Hide Arm/Group Description:

Subjects scheduled for surgery

BKM120: 100 mg once daily, orally, for 8-12 days prior to surgery

Surgery: Surgery

BKM120: 100 mg once daily, orally, for 28-day cycles

Participants continued treatment until disease progression or unacceptable toxicity.

Overall Number of Participants Analyzed 15
Mean (Standard Deviation)
Unit of Measure: ug*h/mL
Day 1 1.42  (0.50)
Day 8 3.27  (1.43)
11.Secondary Outcome
Title AUC0-5h Accumulation Ratio of BKM120 Day 1 and Day 8 [Cohort 1]
Hide Description

Plasma concentrations of BKM120 were analyzed by a validated liquid chromatography-tandem mass spectrometry assay developed by Novartis Pharma AG. Standard Pk parameters were determined using non-compartmental methods.

The accumulation ratio is day 8/day 1.

Time Frame On days 1 and 8 (+/- 1 day) prior to surgery, 5 blood samples were collected at the following timepoints: pre-dose, and at 0.5, 1.5, 3, and 5 hours post-dose.
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis dataset is comprised of all treated patients.
Arm/Group Title Cohort I: Surgical Subjects
Hide Arm/Group Description:

Subjects scheduled for surgery

BKM120: 100 mg once daily, orally, for 8-12 days prior to surgery

Surgery: Surgery

BKM120: 100 mg once daily, orally, for 28-day cycles

Participants continued treatment until disease progression or unacceptable toxicity.

Overall Number of Participants Analyzed 15
Mean (Full Range)
Unit of Measure: ratio day 8/day 1
2.42
(1.694 to 3.146)
12.Secondary Outcome
Title Time to Maximum Observed Plasma Concentration (Tmax) of BKM120 Day 1 and Day 8 [Cohort 1]
Hide Description Plasma concentrations of BKM120 were analyzed by a validated liquid chromatography-tandem mass spectrometry assay developed by Novartis Pharma AG. Standard Pk parameters were determined using non-compartmental methods.
Time Frame On days 1 and 8 (+/- 1 day) prior to surgery, 5 blood samples were collected at the following timepoints: pre-dose, and at 0.5, 1.5, 3, and 5 hours post-dose.
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis dataset is comprised of all treated patients.
Arm/Group Title Cohort 1: Surgical Subjects
Hide Arm/Group Description:

Subjects scheduled for surgery

BKM120: 100 mg once daily, orally, for 8-12 days prior to surgery

Surgery: Surgery

BKM120: 100 mg once daily, orally, for 28-day cycles

Participants continued treatment until disease progression or unacceptable toxicity.

Overall Number of Participants Analyzed 15
Median (Full Range)
Unit of Measure: hours
Day 1
1.5
(1.5 to 5)
Day 8
1.5
(0.5 to 9)
13.Secondary Outcome
Title Overall Survival (OS) [Cohort 2]
Hide Description Overall survival is defined as the time from date of first dose to death or date last known alive and estimated using Kaplan-Meier (KM) methods.
Time Frame Participants were followed long-term for survival via medical record review. Cohort 2 participants were followed for survival up to 52 months in this study cohort.
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis dataset is comprised of all treated participants.
Arm/Group Title Cohort 2: Non-surgical Subjects
Hide Arm/Group Description:

Subjects not candidates for surgery

BKM120: 100 mg once daily, orally, for 28-day cycles

Participants continued treatment until disease progression or unacceptable toxicity.

Overall Number of Participants Analyzed 50
Median (95% Confidence Interval)
Unit of Measure: months
9.8
(8.4 to 12.4)
14.Secondary Outcome
Title Progression-Free Survival (PFS) [Cohort 2]
Hide Description PFS is defined as the time from first dose to the earliest documentation of disease progression or death. Participants alive without evidence of PD were censored at the date of last disease assessment. Progressive disease was established based on Response Assessment in Neuro-Oncology (RANO) criteria (Wen et al JCO 2010). See outcome measure #2.
Time Frame Participants were assessed radiologically every other cycle on treatment and off-treatment via medical record review until death. Cohort 2 participants were followed for progression-free survival up to 12 months in this study cohort.
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis dataset is comprised of all treated participants.
Arm/Group Title Cohort 2: Non-surgical Subjects
Hide Arm/Group Description:

Subjects not candidates for surgery

BKM120: 100 mg once daily, orally, for 28-day cycles

Participants continued treatment until disease progression or unacceptable toxicity.

Overall Number of Participants Analyzed 50
Median (95% Confidence Interval)
Unit of Measure: months
1.7
(1.4 to 2.7)
15.Secondary Outcome
Title Grade 3-5 Treatment-Related Toxicity Rate
Hide Description The percentage of patients who experienced any grade 3-5 treatment-related adverse event based on CTCAEv4 as reported on case report forms.
Time Frame Adverse events experienced by participants are collected and reported throughout treatment with study drug (from initiation of study medication until 30 days after the last dose of BKM120), maximum timeframe was 2 years.
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis dataset is comprised of all treated patients.
Arm/Group Title Cohorts 1: Surgical Subjects Cohorts 2: Non-surgical Subjects
Hide Arm/Group Description:

Subjects scheduled for surgery

BKM120: 100 mg once daily, orally, for 8-12 days prior to surgery

Surgery: Surgery

BKM120: 100 mg once daily, orally, for 28-day cycles

Patients continued treatment until disease progression or unacceptable toxicity.

Subjects not candidates for surgery

BKM120: 100 mg once daily, orally, for 28-day cycles

Patients continued treatment until disease progression or unacceptable toxicity.

Overall Number of Participants Analyzed 15 50
Measure Type: Number
Number (90% Confidence Interval)
Unit of Measure: percentage of patients
40.0
(19.1 to 64.0)
32.0
(21.2 to 44.5)
Time Frame Adverse events experienced by participants are collected and reported throughout treatment with study drug (from initiation of study medication until 30 days after the last dose of BKM120), maximum timeframe was 2 years.
Adverse Event Reporting Description

The following are considered 'serious' adverse events (SAEs) per protocol:

  • ALL Grade 5 (fatal) Events
  • ALL Grade 4 (life threatening or disabling) Events – Unless both Expected AND specifically listed in protocol as not requiring reporting
  • ANY Grade 2 (moderate) or Grade 3 (severe) Event that is both Unexpected and deemed at least Possibly Related to study intervention Other AEs: Remaining AEs (maximum grade by toxicity type) without regard to treatment attribution.
 
Arm/Group Title Cohorts 1: Surgical Subjects Cohorts 2: Non-surgical Subjects
Hide Arm/Group Description

Subjects scheduled for surgery

BKM120: 100 mg once daily, orally, for 8-12 days prior to surgery

Surgery: Surgery

BKM120: 100 mg once daily, orally, for 28-day cycles

Patients continued treatment until disease progression or unacceptable toxicity.

Subjects not candidates for surgery

BKM120: 100 mg once daily, orally, for 28-day cycles

Patients continued treatment until disease progression or unacceptable toxicity.

All-Cause Mortality
Cohorts 1: Surgical Subjects Cohorts 2: Non-surgical Subjects
Affected / at Risk (%) Affected / at Risk (%)
Total   0/15 (0.00%)      2/50 (4.00%)    
Show Serious Adverse Events Hide Serious Adverse Events
Cohorts 1: Surgical Subjects Cohorts 2: Non-surgical Subjects
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   5/15 (33.33%)      12/50 (24.00%)    
Ear and labyrinth disorders     
Tinnitus  1  1/15 (6.67%)  1 0/50 (0.00%)  0
Vestibular disorder  1  1/15 (6.67%)  1 0/50 (0.00%)  0
Gastrointestinal disorders     
Constipation  1  0/15 (0.00%)  0 1/50 (2.00%)  1
Infections and infestations     
Wound Infection  1  0/15 (0.00%)  0 1/50 (2.00%)  1
Investigations     
Lipase Increased  1  0/15 (0.00%)  0 3/50 (6.00%)  3
Lymphocyte count decreased  1  1/15 (6.67%)  1 0/50 (0.00%)  0
Platelet count decreased  1  1/15 (6.67%)  1 0/50 (0.00%)  0
Serum amylase increased  1  1/15 (6.67%)  2 2/50 (4.00%)  3
Weight loss  1  1/15 (6.67%)  1 0/50 (0.00%)  0
White blood cell decreased  1  1/15 (6.67%)  1 0/50 (0.00%)  0
Metabolism and nutrition disorders     
Hypophosphatemia  1  0/15 (0.00%)  0 2/50 (4.00%)  3
Musculoskeletal and connective tissue disorders     
Chest wall pain  1  0/15 (0.00%)  0 1/50 (2.00%)  1
Nervous system disorders     
Edema cerebral  1  0/15 (0.00%)  0 1/50 (2.00%)  1
Headache  1  1/15 (6.67%)  1 0/50 (0.00%)  0
Leukoencephalopathy  1  0/15 (0.00%)  0 1/50 (2.00%)  1
Seizure  1  1/15 (6.67%)  2 0/50 (0.00%)  0
Spasticity  1  0/15 (0.00%)  0 1/50 (2.00%)  1
Psychiatric disorders     
Psychosis  1  0/15 (0.00%)  0 1/50 (2.00%)  1
Respiratory, thoracic and mediastinal disorders     
Dyspnea  1  0/15 (0.00%)  0 1/50 (2.00%)  1
Cough  1  0/15 (0.00%)  0 1/50 (2.00%)  1
Skin and subcutaneous tissue disorders     
Photosensitivity  1  0/15 (0.00%)  0 1/50 (2.00%)  2
Vascular disorders     
Thromboembolic event  1  0/15 (0.00%)  0 1/50 (2.00%)  1
1
Term from vocabulary, CTCAE v. 4
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 4%
Cohorts 1: Surgical Subjects Cohorts 2: Non-surgical Subjects
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   15/15 (100.00%)      50/50 (100.00%)    
Blood and lymphatic system disorders     
Anemia  1  1/15 (6.67%)  6 0/50 (0.00%)  0
Cardiac disorders     
Sinus bradycardia  1  2/15 (13.33%)  2 1/50 (2.00%)  1
Ear and labyrinth disorders     
Hearing Impaired  1  2/15 (13.33%)  2 2/50 (4.00%)  2
Tinnitus  1  0/15 (0.00%)  0 2/50 (4.00%)  2
Endocrine disorders     
Hypothyroidism  1  1/15 (6.67%)  1 0/50 (0.00%)  0
Cushingoid  1  0/15 (0.00%)  0 2/50 (4.00%)  2
Eye disorders     
Blurred vision  1  1/15 (6.67%)  1 4/50 (8.00%)  5
Cataract  1  1/15 (6.67%)  1 1/50 (2.00%)  1
Eye disorders - Other, specify: Left visual field cut/difficulty  1  1/15 (6.67%)  1 1/50 (2.00%)  1
Eye disorders - Other, specify: Eye Disorder:Dyplopia-Double Vision  1  1/15 (6.67%)  1 0/50 (0.00%)  0
Eye disorders - Other, specify: Quadranopsia, right  1  1/15 (6.67%)  1 0/50 (0.00%)  0
Optic nerve disorder  1  0/15 (0.00%)  0 2/50 (4.00%)  2
Gastrointestinal disorders     
Constipation  1  2/15 (13.33%)  4 8/50 (16.00%)  8
Diarrhea  1  5/15 (33.33%)  8 12/50 (24.00%)  15
Mucositis oral  1  3/15 (20.00%)  3 6/50 (12.00%)  6
Nausea  1  6/15 (40.00%)  6 8/50 (16.00%)  8
Dyspepsia  1  1/15 (6.67%)  1 0/50 (0.00%)  0
Abdominal pain  1  0/15 (0.00%)  0 3/50 (6.00%)  3
Vomiting  1  0/15 (0.00%)  0 3/50 (6.00%)  4
Fecal incontinence  1  0/15 (0.00%)  0 4/50 (8.00%)  4
General disorders     
Fatigue  1  11/15 (73.33%)  23 28/50 (56.00%)  41
Irritability  1  1/15 (6.67%)  1 3/50 (6.00%)  3
Chills  1  0/15 (0.00%)  0 2/50 (4.00%)  2
Edema face  1  1/15 (6.67%)  1 2/50 (4.00%)  2
Fever  1  1/15 (6.67%)  1 0/50 (0.00%)  0
Pain  1  3/15 (20.00%)  3 0/50 (0.00%)  0
Gait disturbance  1  0/15 (0.00%)  0 9/50 (18.00%)  10
Infections and infestations     
Conjunctivitis infective  1  1/15 (6.67%)  1 0/50 (0.00%)  0
Papulopustular rash  1  1/15 (6.67%)  1 0/50 (0.00%)  0
Infections and infestations - Other, specify: varicella-zoster virus infection  1  1/15 (6.67%)  1 0/50 (0.00%)  0
Mucosal infection  1  1/15 (6.67%)  1 0/50 (0.00%)  0
Upper respiratory infection  1  1/15 (6.67%)  1 1/50 (2.00%)  1
Urinary tract infection  1  0/15 (0.00%)  0 2/50 (4.00%)  2
Wound infection  1  0/15 (0.00%)  0 2/50 (4.00%)  2
Injury, poisoning and procedural complications     
Bruising  1  0/15 (0.00%)  0 2/50 (4.00%)  3
Fall  1  2/15 (13.33%)  2 4/50 (8.00%)  5
Investigations     
Alanine aminotransferase increased  1  2/15 (13.33%)  2 7/50 (14.00%)  15
Aspartate aminotransferase increased  1  1/15 (6.67%)  1 4/50 (8.00%)  9
Lipase increased  1  2/15 (13.33%)  2 8/50 (16.00%)  9
Lymphocyte count decreased  1  2/15 (13.33%)  5 2/50 (4.00%)  2
Platelet count decreased  1  3/15 (20.00%)  4 7/50 (14.00%)  15
Serum amylase increased  1  3/15 (20.00%)  3 5/50 (10.00%)  8
White blood cell decreased  1  2/15 (13.33%)  2 5/50 (10.00%)  5
Alkaline phosphatase increased  1  1/15 (6.67%)  1 1/50 (2.00%)  1
Blood bilirubin increased  1  1/15 (6.67%)  1 1/50 (2.00%)  1
Neutrophil count decreased  1  1/15 (6.67%)  1 0/50 (0.00%)  0
Weight loss  1  1/15 (6.67%)  1 0/50 (0.00%)  0
Weight gain  1  0/15 (0.00%)  0 2/50 (4.00%)  3
Metabolism and nutrition disorders     
Anorexia  1  2/15 (13.33%)  3 3/50 (6.00%)  3
Hyperglycemia  1  6/15 (40.00%)  9 25/50 (50.00%)  66
Hypophosphatemia  1  2/15 (13.33%)  7 2/50 (4.00%)  3
Hyperkalemia  1  1/15 (6.67%)  1 1/50 (2.00%)  1
Dehydration  1  2/15 (13.33%)  2 0/50 (0.00%)  0
Hypoalbuminemia  1  1/15 (6.67%)  2 0/50 (0.00%)  0
Hypocalcemia  1  1/15 (6.67%)  1 0/50 (0.00%)  0
Hypokalemia  1  3/15 (20.00%)  4 1/50 (2.00%)  3
Hypomagnesemia  1  1/15 (6.67%)  1 0/50 (0.00%)  0
Hyponatremia  1  1/15 (6.67%)  2 2/50 (4.00%)  2
Musculoskeletal and connective tissue disorders     
Chest wall pain  1  0/15 (0.00%)  0 2/50 (4.00%)  2
Neck pain  1  0/15 (0.00%)  0 2/50 (4.00%)  2
Arthralgia  1  1/15 (6.67%)  1 1/50 (2.00%)  1
Back pain  1  2/15 (13.33%)  3 3/50 (6.00%)  3
Generalized muscle weakness  1  2/15 (13.33%)  2 5/50 (10.00%)  7
Muscle weakness left-sided  1  1/15 (6.67%)  1 2/50 (4.00%)  3
Muscle weakness right-sided  1  1/15 (6.67%)  1 1/50 (2.00%)  1
Nervous system disorders     
Ataxia  1  3/15 (20.00%)  4 2/50 (4.00%)  2
Cognitive disturbance  1  1/15 (6.67%)  1 7/50 (14.00%)  7
Dizziness  1  2/15 (13.33%)  2 4/50 (8.00%)  4
Dysarthria  1  1/15 (6.67%)  1 1/50 (2.00%)  1
Dysesthesia  1  1/15 (6.67%)  1 1/50 (2.00%)  1
Dysphasia  1  2/15 (13.33%)  2 9/50 (18.00%)  10
Headache  1  2/15 (13.33%)  2 17/50 (34.00%)  21
Intracranial hemorrhage  1  1/15 (6.67%)  1 0/50 (0.00%)  0
Memory impairment  1  1/15 (6.67%)  1 9/50 (18.00%)  10
Nervous system disorders - Other, specify: left tongue deviation  1  1/15 (6.67%)  1 0/50 (0.00%)  0
Neuralgia  1  1/15 (6.67%)  1 0/50 (0.00%)  0
Seizure  1  4/15 (26.67%)  6 11/50 (22.00%)  14
Stroke  1  1/15 (6.67%)  1 0/50 (0.00%)  0
Concentration impairment  1  0/15 (0.00%)  0 2/50 (4.00%)  2
Lethargy  1  0/15 (0.00%)  0 2/50 (4.00%)  3
Pyramidal tract syndrome  1  0/15 (0.00%)  0 4/50 (8.00%)  4
Somnolence  1  0/15 (0.00%)  0 2/50 (4.00%)  2
Nervous system disorders - Other, specify: Aphasia  1  0/15 (0.00%)  0 3/50 (6.00%)  3
Psychiatric disorders     
Agitation  1  1/15 (6.67%)  1 6/50 (12.00%)  6
Anxiety  1  3/15 (20.00%)  6 11/50 (22.00%)  18
Depression  1  6/15 (40.00%)  9 11/50 (22.00%)  20
Confusion  1  1/15 (6.67%)  2 6/50 (12.00%)  6
Insomnia  1  1/15 (6.67%)  1 5/50 (10.00%)  7
Libido decreased  1  1/15 (6.67%)  1 0/50 (0.00%)  0
Personality change  1  0/15 (0.00%)  0 2/50 (4.00%)  2
Renal and urinary disorders     
Urinary frequency  1  1/15 (6.67%)  1 5/50 (10.00%)  6
Renal calculi  1  1/15 (6.67%)  1 0/50 (0.00%)  0
Urinary incontinence  1  1/15 (6.67%)  1 5/50 (10.00%)  7
Respiratory, thoracic and mediastinal disorders     
Cough  1  0/15 (0.00%)  0 3/50 (6.00%)  3
Sore throat  1  0/15 (0.00%)  0 2/50 (4.00%)  2
Skin and subcutaneous tissue disorders     
Dry skin  1  0/15 (0.00%)  0 4/50 (8.00%)  4
Pruritis  1  0/15 (0.00%)  0 5/50 (10.00%)  6
Rash acneiform  1  4/15 (26.67%)  9 5/50 (10.00%)  10
Rash maculo-papular  1  1/15 (6.67%)  2 4/50 (8.00%)  6
Photosensitivity  1  1/15 (6.67%)  1 1/50 (2.00%)  2
Purpura  1  1/15 (6.67%)  2 0/50 (0.00%)  0
Skin and subcutaneous tissue disorders - Other, specify: Rash, unspecified  1  1/15 (6.67%)  1 2/50 (4.00%)  2
Skin/subcutaneous tissue disorders; Other, specify: Significant confluent erythema covering essentia  1  1/15 (6.67%)  1 0/50 (0.00%)  0
Erythema multiforme  1  0/15 (0.00%)  0 3/50 (6.00%)  3
Scalp pain  1  1/15 (6.67%)  1 0/50 (0.00%)  0
Skin and subcutaneous tissue disorders - Other, specify: mild pain at incision site  1  1/15 (6.67%)  1 0/50 (0.00%)  0
Skin and subcutaneous tissue disorders - Other, specify: Fungal Rash  1  1/15 (6.67%)  1 0/50 (0.00%)  0
Surgical and medical procedures     
Surgical and medical procedures - Other, specify: Surgery (post-treatment craniotomy)  1  0/15 (0.00%)  0 2/50 (4.00%)  2
Vascular disorders     
Hypertension  1  0/15 (0.00%)  0 7/50 (14.00%)  15
Thromboembolic event  1  1/15 (6.67%)  1 3/50 (6.00%)  3
Hypotension  1  1/15 (6.67%)  1 0/50 (0.00%)  0
1
Term from vocabulary, CTCAE v. 4
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title: Patrick Y. Wen, MD, Director, DFCI Center for Neuro-Oncology
Organization: Dana-Farber Cancer Institute
Phone: 617-632-2166
Responsible Party: Patrick Y. Wen, MD, Dana-Farber/Brigham and Women's Cancer Center
ClinicalTrials.gov Identifier: NCT01339052     History of Changes
Other Study ID Numbers: 11-033
CBKM120XUS07T ( Other Identifier: Novartis )
First Submitted: April 18, 2011
First Posted: April 20, 2011
Results First Submitted: March 14, 2017
Results First Posted: June 14, 2017
Last Update Posted: March 19, 2019