Please note that the copy function is not enabled for this field.
If you wish to
modify
existing outcomes, please copy and paste the current outcome text into the Update field.
LOGIN
CREATE ACCOUNT
LOGIN
CREATE ACCOUNT
MY TRIALS
REGISTER TRIAL
FAQs
HINTS AND TIPS
DEFINITIONS
Trial Review
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 endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this
information for consumers
Download to PDF
Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/ct2/show/NCT01934361
Registration number
NCT01934361
Ethics application status
Date submitted
20/08/2013
Date registered
4/09/2013
Date last updated
9/12/2020
Titles & IDs
Public title
Phase Ib/II Study of Buparlisib Plus Carboplatin or Lomustine in Patients With Recurrent Glioblastoma Multiforme
Query!
Scientific title
Phase Ib/II Multicenter Study of Buparlisib Plus Carboplatin or Lomustine in Patients With Recurrent Glioblastoma Multiforme
Query!
Secondary ID [1]
0
0
2013-003129-27
Query!
Secondary ID [2]
0
0
CBKM120E2102
Query!
Universal Trial Number (UTN)
Query!
Trial acronym
Query!
Linked study record
Query!
Health condition
Health condition(s) or problem(s) studied:
Recurrent Glioblastoma Multiforme
0
0
Query!
Condition category
Condition code
Cancer
0
0
0
0
Query!
Brain
Query!
Other
0
0
0
0
Query!
Research that is not of generic health relevance and not applicable to specific health categories listed above
Query!
Intervention/exposure
Study type
Interventional
Query!
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.
Query!
Intervention code [1]
0
0
Treatment: Drugs
Query!
Comparator / control treatment
Query!
Control group
Query!
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]
Query!
Assessment method [1]
0
0
Maximum Tolerated Dose (MTD) is defined as the highest BKM120 dosage that does not cause medically unacceptable Dose Limiting Toxicities (DLTs) in more than 35% of the treated patients during the first cycle of treatment. DLT is defined as treatment-related toxicity occurring during the phase Ib cycle 1 and meeting specific protocol-predefined criteria. The information will be integrated in a Bayesian logistic regression model with overdose control to estimate the MTD.
Query!
Timepoint [1]
0
0
Cycle 1 (21 days carboplatin combination or 42 days lomustine combination )
Query!
Primary outcome [2]
0
0
12 week Progression Free Survival (PFS) rate (Phase II- Carboplatin combination)
Query!
Assessment method [2]
0
0
12-week Progression Free Survival (PFS) is defined as the percentage of patients who are progression free 12 weeks after the date of the start of the treatment ("success"). Patients who progressed, died or discontinued within the 12 weeks of observation are counted as "failure".
Query!
Timepoint [2]
0
0
12 weeks
Query!
Primary outcome [3]
0
0
Progression Free Survival (PFS) [phase II lomustine combinations]
Query!
Assessment method [3]
0
0
Progression Free Survival (PFS) is defined as the time from date of randomization to the date of the event, which is the first radiologically documented disease progression [per local investigator assessment according to Response Assessment in Neuro-Oncology (RANO) criteria] or death due to any cause.
Query!
Timepoint [3]
0
0
Randomization until date of the event (expected average 3 months).
Query!
Secondary outcome [1]
0
0
Frequency and severity of Adverse Events (AEs) [Phase Ib, Phase II, all treatment arms]
Query!
Assessment method [1]
0
0
The incidence of Adverse Events (AEs) summarized by system organ class and or preferred term, severity (based on Common Terminology Criteria for Adverse Events (CTCAE) grades version 4), type of AE, relation to study treatment.
Query!
Timepoint [1]
0
0
Until 30 days after treatment discontinuation
Query!
Secondary outcome [2]
0
0
Overall Response Rate (ORR) as per Response Assessment in Neuro-Oncology (RANO) [Phase Ib , both combinations]
Query!
Assessment method [2]
0
0
Overall response rate (ORR) is defined as the proportion of patients with a best overall response of complete response (CR) or partial response (PR), based on the investigator assessment as per Response Assessment in Neuro-Oncology (RANO) criteria.
Query!
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
Query!
Secondary outcome [3]
0
0
Progression Free Survival (PFS) [Phase Ib- both combinations]
Query!
Assessment method [3]
0
0
Progression Free Survival (PFS) is defined as time from date of treatment start to the date of the event, which is the first radiologically documented disease progression or death due to any cause per local investigator assessment.
Query!
Timepoint [3]
0
0
Time from treatment start to the date of the event (expected average 3 months)
Query!
Secondary outcome [4]
0
0
Overall response rate (ORR) [Phae II, carboplatin combination]
Query!
Assessment method [4]
0
0
Overall response rate (ORR) is defined as the proportion of patients with a best overall response of complete response (CR) or partial response (PR), based on the investigator assessment as per Response Assessment in Neuro-Oncology (RANO) criteria.
Query!
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
Query!
Secondary outcome [5]
0
0
Progression Free Survival (PFS) [Phase II, carboplatin combination]
Query!
Assessment method [5]
0
0
Progression Free Survival (PFS) is defined as time from date of treatment start to the date of the event, which is the first radiologically documented disease progression or death due to any cause per local investigator assessment.
Query!
Timepoint [5]
0
0
Time from treatment start to the date of the event (Expected average: 3 months)
Query!
Secondary outcome [6]
0
0
24 week Progression Free Survival (PFS) rate (Phase II carboplatin combination)
Query!
Assessment method [6]
0
0
24 weeks Progression Free Survival (PFS) is defined as the percentage of patients who are progression free 24 weeks after the date of the start of the treatment ("success"). Patients who progressed, died or discontinued within the 24 weeks of observation are counted as "failure".
Query!
Timepoint [6]
0
0
24 weeks
Query!
Secondary outcome [7]
0
0
Overall Survival (OS) (Phase II Carboplatin combination)
Query!
Assessment method [7]
0
0
Overall survival (OS) is defined as the time from the date of randomization for buparlisib + lomustine / placebo + lomustine Phase II, or the time from the first study drug intake for buparlisib + carboplatin Phase II, to the date of death due to any cause.
Query!
Timepoint [7]
0
0
12 months
Query!
Secondary outcome [8]
0
0
Overall Response Rate (ORR) (Phase II Lomustine combinations)
Query!
Assessment method [8]
0
0
Overall response rate (ORR) is defined as the proportion of patients with a best overall response of complete response (CR) or partial response (PR), based on the investigator assessment as per Response Assessment in Neuro-Oncology (RANO) criteria.
Query!
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
Query!
Secondary outcome [9]
0
0
12 week Progression Free Survival (PFS) rate (Phase II- lomustine combinations)
Query!
Assessment method [9]
0
0
12-week Progression Free Survival (PFS) is defined as the percentage of patients who are progression free 12 weeks after the date of the start of the treatment ("success"). Patients who progressed, died or discontinued within the 12 weeks of observation are counted as "failure".
Query!
Timepoint [9]
0
0
12 weeks
Query!
Secondary outcome [10]
0
0
24 week Progression Free Survival (PFS) rate (Phase II- lomustine combinations)
Query!
Assessment method [10]
0
0
24 weeks Progression Free Survival (PFS) is defined as the percentage of patients who are progression free 24 weeks after the date of the start of the treatment ("success"). Patients who progressed, died or discontinued within the 24 weeks of observation are counted as "failure".
Query!
Timepoint [10]
0
0
24 weeks
Query!
Secondary outcome [11]
0
0
Overall survival (OS) [Phase II lomustine combinations]
Query!
Assessment method [11]
0
0
Overall survival (OS) is defined as the time from the date of randomization for buparlisib + lomustine / placebo + lomustine Phase II, or the time from the first study drug intake for buparlisib + carboplatin Phase II, to the date of death due to any cause.
Query!
Timepoint [11]
0
0
12 months
Query!
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).
Query!
Minimum age
18
Years
Query!
Query!
Maximum age
No limit
Query!
Query!
Sex
Both males and females
Query!
Can healthy volunteers participate?
No
Query!
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.
Query!
Study design
Purpose of the study
Treatment
Query!
Allocation to intervention
Randomised controlled trial
Query!
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Query!
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Query!
Masking / blinding
Open (masking not used)
Query!
Who is / are masked / blinded?
Query!
Query!
Query!
Query!
Intervention assignment
Parallel
Query!
Other design features
Query!
Phase
Phase 1
Query!
Type of endpoint/s
Query!
Statistical methods / analysis
Query!
Recruitment
Recruitment status
Completed
Query!
Data analysis
Query!
Reason for early stopping/withdrawal
Query!
Other reasons
Query!
Date of first participant enrolment
Anticipated
Query!
Actual
28/02/2014
Query!
Date of last participant enrolment
Anticipated
Query!
Actual
Query!
Date of last data collection
Anticipated
Query!
Actual
7/07/2016
Query!
Sample size
Target
Query!
Accrual to date
Query!
Final
35
Query!
Recruitment in Australia
Recruitment state(s)
VIC
Query!
Recruitment hospital [1]
0
0
Novartis Investigative Site - Heidelberg
Query!
Recruitment hospital [2]
0
0
Novartis Investigative Site - Parkville
Query!
Recruitment postcode(s) [1]
0
0
3084 - Heidelberg
Query!
Recruitment postcode(s) [2]
0
0
3050 - Parkville
Query!
Recruitment outside Australia
Country [1]
0
0
United States of America
Query!
State/province [1]
0
0
Arizona
Query!
Country [2]
0
0
United States of America
Query!
State/province [2]
0
0
Arkansas
Query!
Country [3]
0
0
United States of America
Query!
State/province [3]
0
0
Illinois
Query!
Country [4]
0
0
United States of America
Query!
State/province [4]
0
0
Massachusetts
Query!
Country [5]
0
0
United States of America
Query!
State/province [5]
0
0
Texas
Query!
Country [6]
0
0
Belgium
Query!
State/province [6]
0
0
Leuven
Query!
Country [7]
0
0
Canada
Query!
State/province [7]
0
0
Ontario
Query!
Country [8]
0
0
France
Query!
State/province [8]
0
0
Marseille Cedex 05
Query!
Country [9]
0
0
France
Query!
State/province [9]
0
0
Paris Cedex 13
Query!
Country [10]
0
0
France
Query!
State/province [10]
0
0
Saint Herblain cedex
Query!
Country [11]
0
0
Spain
Query!
State/province [11]
0
0
Catalunya
Query!
Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Query!
Name
Novartis Pharmaceuticals
Query!
Address
Query!
Country
Query!
Ethics approval
Ethics application status
Query!
Summary
Brief summary
This is a multi-center, phase Ib/ II study (two parts) with patients that had recurrent
glioblastoma multiforme. The first part (phase Ib) was to investigate the maximum tolerated
dose/Recommended phase ll dose (MTD/RP2D) of once daily buparlisib in combination with
every-three-week carboplatin or buparlisib once daily in combination with every-six-week
lomustine (CCNU) using a Bayesian model. Once MTD/ RP2D is established in either of the 2
arms, the corresponding phase II portion of the study was to start. Phase II was to assess
the treatment effect of buparlisib in combination with carboplatin in terms of Progression
Free Survival (PFS) and was to compare the treatment effect of buparlisib with lomustine
versus lomustine plus placebo in terms of PFS.
A preliminary assessment for both combinations (buparlisib plus carboplatin or lomustine)
demonstrated that there was not enough antitumor activity compared to historical data with
single agent carboplatin or lomustine. Based on the overall safety profile, and preliminary
anti-tumor activity observed in this study, Novartis decided that no additional patients
would be enrolled into this study. As a consequence, the Phase II part of the study was not
conducted.
Query!
Trial website
https://clinicaltrials.gov/ct2/show/NCT01934361
Query!
Trial related presentations / publications
Query!
Public notes
Query!
Contacts
Principal investigator
Name
0
0
Novartis Pharmaceuticals
Query!
Address
0
0
Novartis Pharmaceuticals
Query!
Country
0
0
Query!
Phone
0
0
Query!
Fax
0
0
Query!
Email
0
0
Query!
Contact person for public queries
Name
0
0
Query!
Address
0
0
Query!
Country
0
0
Query!
Phone
0
0
Query!
Fax
0
0
Query!
Email
0
0
Query!
Contact person for scientific queries
Summary Results
For IPD and results data, please see
https://clinicaltrials.gov/ct2/show/NCT01934361
Download to PDF