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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT01473901




Registration number
NCT01473901
Ethics application status
Date submitted
18/08/2011
Date registered
17/11/2011
Date last updated
13/09/2017

Titles & IDs
Public title
A Phase I Dose Escalation Study of BKM120 With Radiation Therapy and Temozolomide in Patients With Newly Diagnosed Glioblastoma
Scientific title
A Phase I, Two-stage, Multi-center, Open Label, Dose-escalation Study of BKM120 in Combination With Adjuvant Temozolomide and With Concomitant Radiation Therapy and Temozolomide in Patients With Newly Diagnosed Glioblastoma
Secondary ID [1] 0 0
2011-001157-87
Secondary ID [2] 0 0
CBKM120E2101
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Glioblastoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Brain

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - BKM120 + temozolomide
Treatment: Drugs - BKM120 +temozolomide with/without radiotherapy

Experimental: BKM120 + Temozolomide (Concomitant Phase) - Cranial radiation: Days 1 - 5 every 7 days for 42 days60 Gy in 30 fractions; Temozolomide: 75 mg/m2 Daily, orally; BKM120: 0, or 40, or 60, or 80 mg/d Daily, orally or Days 1-5 every 7 days, orally

Experimental: BKM120 + temozolomide with/without radiotherapy - Adjuvant phase cycle 1:
Temozolomide ?150 mg/m2 - Days 1 - 5 every 28 days Daily; BKM120 60, or 80, or 100 mg/d;
Adjuvant phase cycle 2+:
Temozolomide 200* mg/m2 - Day 1 ~ 5 every 28 days Daily BKM120 0, or 40, or 60, or 80 or 100 mg/d


Treatment: Drugs: BKM120 + temozolomide
The investigational drug, BKM120, will be supplied as 10-mg and 50-mg hard gelatin capsules. BKM120 will be administered on a once daily dosing schedule at a dose of 40 mg, or 60 mg, or 80 mg, or 100 mg (p.o.), in combination with the approved dosing of temozolomide and SoC delivery of cranial irradiation for GBM. The patient will be dosed with BKM120 on a flat scale of mg/day and the dose of BKM120 will not be adjusted to body weight or body surface area. Patients should not eat for 2 hours after the administration of BKM120. Temozolomide in 5 mg, 20 mg, 100 mg, 140 mg, 180 mg or 250 mg capsules will be administered in combination with the investigational drug BKM120.

Treatment: Drugs: BKM120 +temozolomide with/without radiotherapy
The investigational drug, BKM120, will be supplied as 10-mg and 50-mg hard gelatin capsules. BKM120 will be administered on a continuous once daily dosing schedule at a dose of 40 mg, or 60 mg, or 80 mg, or 100 mg (p.o.), in combination with the approved dosing of temozolomide and SoC delivery of cranial irradiation for GBM. The patient will be dosed with BKM120 on a flat scale of mg/day and the dose of BKM120 will not be adjusted to body weight or body surface area. Patients should not eat for 2 hours after the administration of BKM120. Temozolomide in 5 mg, 20 mg, 100 mg, 140 mg, 180 mg or 250 mg capsules will be administered in combination with the investigational drug BKM120.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Dose Limiting Toxicity (DLT) - Per DLT criteria as defined in protocol
Timepoint [1] 0 0
Concomitant phase (42 days), adjuvant phase cycle 1 (28-day cycle), adjuvant phase cycles 2 (28-day cycle)
Secondary outcome [1] 0 0
No of participants with Adverse events based on abnormal laboratory results, abnormal electrocardiogram (ECG) findings - Per common terminology criteria for adverse events (CTCAE) criteria (version 4.0)
Timepoint [1] 0 0
Baseline, 30 days post the last BKM120 treatment
Secondary outcome [2] 0 0
Objective response rate (ORR) - Antitumor activity will be assessed using the Neuro-Oncology Working Group updated response assessment criteria for high grade gliomas - per RANO criteria.
Timepoint [2] 0 0
Baseline, 18 months after first BKM120 treatment
Secondary outcome [3] 0 0
Progression free survival (PFS) - Per patient survival follow up feedbacks
Timepoint [3] 0 0
at 12 months and at 18 months
Secondary outcome [4] 0 0
Overall survival (OS) - Per patient survival follow up feedbacks
Timepoint [4] 0 0
Until death or consent withdrawal
Secondary outcome [5] 0 0
Plasma concentration-time profiles and basic pharmacokinetic parameters of BKM120 and temozolomide (Cmax, tmas, AUC, half-life) - Standard bioanalytical-pharmacokinetic (PK) analysis on PK samples for BKM120 and temozolomide.
Timepoint [5] 0 0
baseline, Day 1, 8, 15, 28 in concomitant phase, Cycle 1 Day 1, 5 and Cycle 2 Day1, 5 at adjuvant phase (28-day per cycle)

Eligibility
Key inclusion criteria
- Patient is = 18 years of age on the day of consent signature

- Patient with histologically demonstrated, previously untreated glioblastoma

- Patient may have received initial treatment for GBM as follows:

- For patients enrolled into Stage I, they must have received at least 75% of
planned radiotherapy (60 Gy) with temozolomide treatment during the concomitant
phase have documentation that the patient's absolute neutrophil count (ANC) is =
1.5 x 109/L, platelet count is = 100 x 109/L, and there was no CTC grade 2 or
above nonhematological toxicity (except for alopecia, nausea, vomiting) during
the concomitant phase treatment be within = 4 weeks but = 6 weeks following the
completion of temozolomide in the concomitant phase

- For patients enrolled into Stage II, they must be within = 2 weeks but = 6 weeks
after primary GBM resection/biopsy The patient must have recovered from the
definitive surgical procedure for GBM

- Patient is able to be assessed by periodic dynamic contrast enhanced magnetic
resonance imaging (DCE-MRI) scan

- Patient has Karnofsky performance status >= 60

- Patient has adequate bone marrow and organ function
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Patient has received previous treatment with PI3K and/or mTOR inhibitors for GBM or
for pre-existing neoplasm transformed to GBM. Patient has received any prior
anti-neoplastic therapy for BKM, except for the treatment allowed in inclusion
criteria

- Patient has any tumor progression after definitive GBM resection/ biopsy, except for
the transformation from previous low grade glioma. Patient with a concurrent
malignancy or malignancy within 3 years of study enrollment (with the exception of
adequately treated, basal or squamous cell carcinoma, non-melanomatous skin cancer or
curatively resected cervical cancer)

- Patient who had not recovered to grade 1 or better from any adverse events (except
alopecia, nausea, vomiting) related to previous antineoplastic therapy before
screening procedures are initiated, as allowed in inclusion criteria

- Patient has any of the following baseline mood disorders (not attributable to GBM) as
judged by the Investigator or a Psychiatrist, or meets the cut-off score of = 12 in
the PHQ- 9 or a cut-off of = 15 in the GAD-7 mood scale for reasons not attributable
to GBM; or selects a positive response of '1, 2, 3' to question number 9 regarding
potential for suicidal thoughts or ideation in the PHQ-9 (independent of the total
score of the PHQ-9)

- Medically documented history of or active major depressive episode, bipolar disorder
(I or II), obsessive-compulsive disorder, schizophrenia, a history of suicidal attempt
or ideation, or homicidal ideation (immediate risk of doing harm to others)

- Active severe personality disorders (defined according to DSM-IV). Note: for patients
with psychotropic treatments ongoing at baseline, the dose and the schedule should not
be modified within the previous 6 weeks prior to start of study drug.

- = CTCAE grade 3 anxiety

- Patient who is concurrently using any other approved or investigational
anti-neoplastic agent

- Patient who has undergone the following invasive procedures: Major surgical procedure,
open biopsy or significant traumatic injury < 14 days prior to starting study drug or
has not recovered from side effects of such therapy, anticipation of need for invasive
surgical procedure during the course of the study, biopsy within 7 days prior to
starting study drug

- Patient has poorly controlled diabetes mellitus (HbA1c > 8%)

- Patient is currently receiving increasing or chronic treatment with corticosteroids or
another immunosuppressive agent

- Patient is currently receiving an enzyme inducing anti-epileptic drug. The patient
must have discontinued EIAED therapy for at least two weeks prior to starting study
drug. Non-enzyme inducing anti-epileptic medication is allowed, except those listed in
the protocol

Other protocol-defined inclusion/exclusion criteria may apply

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 1
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Novartis Investigative Site - Melbourne
Recruitment postcode(s) [1] 0 0
3000 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arkansas
Country [2] 0 0
United States of America
State/province [2] 0 0
Massachusetts
Country [3] 0 0
United States of America
State/province [3] 0 0
Texas
Country [4] 0 0
Canada
State/province [4] 0 0
Ontario
Country [5] 0 0
Spain
State/province [5] 0 0
Catalunya
Country [6] 0 0
Spain
State/province [6] 0 0
Madrid

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Novartis Pharmaceuticals
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This clinical study will assess the doses of BKM120 appropriate for patients with newly
diagnosed glioblastoma when given in combination with radiotherapy and temozolomide.
Trial website
https://clinicaltrials.gov/show/NCT01473901
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Novartis Pharmaceuticals
Address 0 0
Novartis Pharmaceuticals
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications