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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01934361




Registration number
NCT01934361
Ethics application status
Date submitted
20/08/2013
Date registered
4/09/2013

Titles & IDs
Public title
Phase Ib/II Study of Buparlisib Plus Carboplatin or Lomustine in Patients With Recurrent Glioblastoma Multiforme
Scientific title
Phase Ib/II Multicenter Study of Buparlisib Plus Carboplatin or Lomustine in Patients With Recurrent Glioblastoma Multiforme
Secondary ID [1] 0 0
2013-003129-27
Secondary ID [2] 0 0
CBKM120E2102
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Recurrent Glioblastoma Multiforme 0 0
Condition category
Condition code
Cancer 0 0 0 0
Brain
Other 0 0 0 0
Research that is not of generic health relevance and not applicable to specific health categories listed above

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - buparlisib
Treatment: Drugs - carboplatin
Treatment: Drugs - lomustine
Treatment: Drugs - placebo

Experimental: Lomustine+ buparlisib (Phase Ib) -

Experimental: carboplatin+ buparlisib (Phase Ib) -

Experimental: lomustine+ buparlisib (Phase II) -

Placebo comparator: lumustine + placebo (Phase II) -

Experimental: carboplatin+ buparlisib (Phase II) -


Treatment: Drugs: buparlisib
Buparlisib administered orally on a continuous daily schedule. Buparlisib is manufactured as 10mg and 50mg hard gelatin capsules.

Treatment: Drugs: carboplatin
Carboplatin intravenous infusion will be administered at a dose of AUC 5 in a 21 day cycle (every 3 weeks).

Treatment: Drugs: lomustine
Lomustine will be administered as a single oral dose of 100 mg/m² every 6 weeks in a 42 day cycles.

Treatment: Drugs: placebo
Placebo will be administered orally on a continuous QD dosing schedule for cycles of 42 days. Buparlisib matching placebo is manufactured as 10 mg and 50 mg hard gelatin capsules.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of Total Dose-limiting Toxicity (DLT) during Dose Escalation part to determine Maximum Tolerated Dose (MTD) [Phase Ib]
Timepoint [1] 0 0
Cycle 1 (21 days carboplatin combination or 42 days lomustine combination )
Primary outcome [2] 0 0
12 week Progression Free Survival (PFS) rate (Phase II- Carboplatin combination)
Timepoint [2] 0 0
12 weeks
Primary outcome [3] 0 0
Progression Free Survival (PFS) [phase II lomustine combinations]
Timepoint [3] 0 0
Randomization until date of the event (expected average 3 months).
Secondary outcome [1] 0 0
Frequency and severity of Adverse Events (AEs) [Phase Ib, Phase II, all treatment arms]
Timepoint [1] 0 0
Until 30 days after treatment discontinuation
Secondary outcome [2] 0 0
Overall Response Rate (ORR) as per Response Assessment in Neuro-Oncology (RANO) [Phase Ib , both combinations]
Timepoint [2] 0 0
Baseline, every 6 weeks from treatment start until disease progression or until start of another antineoplastic treatment or death which ever occurs first up to 1 year
Secondary outcome [3] 0 0
Progression Free Survival (PFS) [Phase Ib- both combinations]
Timepoint [3] 0 0
Time from treatment start to the date of the event (expected average 3 months)
Secondary outcome [4] 0 0
Overall response rate (ORR) [Phae II, carboplatin combination]
Timepoint [4] 0 0
Baseline, every 6 weeks from treatment start until disease progression or until start of another antineoplastic treatment or death which ever occurs first up to 1 year
Secondary outcome [5] 0 0
Progression Free Survival (PFS) [Phase II, carboplatin combination]
Timepoint [5] 0 0
Time from treatment start to the date of the event (Expected average: 3 months)
Secondary outcome [6] 0 0
24 week Progression Free Survival (PFS) rate (Phase II carboplatin combination)
Timepoint [6] 0 0
24 weeks
Secondary outcome [7] 0 0
Overall Survival (OS) (Phase II Carboplatin combination)
Timepoint [7] 0 0
12 months
Secondary outcome [8] 0 0
Overall Response Rate (ORR) (Phase II Lomustine combinations)
Timepoint [8] 0 0
Baseline, every 6 weeks from treatment start until disease progression or until start of another antineoplastic treatment or death which ever occurs first up to 1 year
Secondary outcome [9] 0 0
12 week Progression Free Survival (PFS) rate (Phase II- lomustine combinations)
Timepoint [9] 0 0
12 weeks
Secondary outcome [10] 0 0
24 week Progression Free Survival (PFS) rate (Phase II- lomustine combinations)
Timepoint [10] 0 0
24 weeks
Secondary outcome [11] 0 0
Overall survival (OS) [Phase II lomustine combinations]
Timepoint [11] 0 0
12 months

Eligibility
Key inclusion criteria
* Patient is an adult = 18 years old at the time of informed consent.
* Patient has histologically confirmed diagnosis of GBM with documented recurrence after first line treatment including radiotherapy and TMZ (SoC), not suitable for curative surgery or re-irradiation.
* Patient has at least one measurable and/or non-measurable lesion as per RANO criteria
* Patient has recovered (to Grade =1) from all clinically significant toxicities related to prior antineoplastic therapies.
* Patient has Karnofsky performance status (KPS) =70%.
* Patient has adequate organ and bone marrow functions:

* Absolute Neutrophils Count (ANC) = 1.5 x 109/L
* Platelets = 100 x 109/L (in case of transfusion stable for =14 days prior to treatment start)
* Hemoglobin = 9.0 g/dL (in case of transfusion stable for =14 days prior to treatment start)
* INR = 1,5
* Serum Creatinine = 1.5 x ULN, or Creatinine Clearance > 45mL/min
* Potassium and calcium (corrected for albumin), sodium and magnesium within institutional normal limits
* Serum Bilirubin = ULN, AST and ALT = ULN
* HbA1c = 8%
* Fasting plasma glucose (FPG) = 120 mg/dL or = 6.7 mmol/L
* Patient has tumor tissues available (archival or fresh).
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Patient has received previous treatment with PI3K inhibitors, lomustine or carboplatin.
* Patient has received previous antineoplastic treatment for recurrent GBM (e.g. VEGF inhibitors, cytotoxic agents).
* Patient has received more than one line of cytotoxic chemotherapy
* Patient has concurrent use of anti-neoplastic agents including investigational therapy
* Patient is currently receiving warfarin or other coumarin derived anti-coagulant, for treatment, prophylaxis or otherwise. Therapy with heparin, low molecular weight heparin (LMWH), or fondaparinux is allowed.
* Patient is currently receiving treatment with drugs known to be moderate or strong inhibitors or inducers of isoenzyme CYP3A. The patient must have discontinued strong inducers for at least one week and must have discontinued strong inhibitors before the treatment is initiated. Switching to a different medication prior to randomization is allowed.
* Patient is currently receiving an enzyme-inducing anti-epileptic drug (EIAED). The patient must have discontinued EIAED therapy for at least two weeks prior to starting study drug.

Other protocol-defined Inclusion/exclusion criteria may apply.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled 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
Parallel
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
28/02/2014
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
7/07/2016
Sample size
Target
Accrual to date
Final
35
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Novartis Investigative Site - Heidelberg
Recruitment hospital [2] 0 0
Novartis Investigative Site - Parkville
Recruitment postcode(s) [1] 0 0
3084 - Heidelberg
Recruitment postcode(s) [2] 0 0
3050 - Parkville
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
Arkansas
Country [3] 0 0
United States of America
State/province [3] 0 0
Illinois
Country [4] 0 0
United States of America
State/province [4] 0 0
Massachusetts
Country [5] 0 0
United States of America
State/province [5] 0 0
Texas
Country [6] 0 0
Belgium
State/province [6] 0 0
Leuven
Country [7] 0 0
Canada
State/province [7] 0 0
Ontario
Country [8] 0 0
France
State/province [8] 0 0
Marseille Cedex 05
Country [9] 0 0
France
State/province [9] 0 0
Paris Cedex 13
Country [10] 0 0
France
State/province [10] 0 0
Saint Herblain cedex
Country [11] 0 0
Spain
State/province [11] 0 0
Catalunya

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

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
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

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT01934361