GlioblastomaPhase 1NCT01473901
A Phase I Dose Escalation Study of BKM120 With Radiation Therapy and Temozolomide in Patients With Newly Diagnosed Glioblastoma
A Phase 1 study testing BKM120 + temozolomide and BKM120 +temozolomide with/without radiotherapy in people with Glioblastoma, run by Novartis Pharmaceuticals at 8 sites in 4 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Glioblastoma
- What is being tested?
- BKM120 + temozolomide and BKM120 +temozolomide with/without radiotherapy
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 38 participants
- Where
- 8 sitesin 4 countries
- Study dates
- 30 Dec 2011to 17 May 2017
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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.
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- ≥ 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
Trial locations and contacts
8 sites in 4 countries.
8 sites in 4 countries
United States3 sites
Dana Farber Cancer Institute SC (1)
Boston, Massachusetts, 02215
Highlands Oncology Group Highlands Oncology
Fayetteville, Arkansas, 72703
University of Texas/MD Anderson Cancer Center MD Anderson DeGrout
Houston, Texas, 77030-4009
Canada2 sites
Novartis Investigative Site
Hamilton, Ontario, L8V 5C2
Novartis Investigative Site
Toronto, Ontario, M5G 1Z6
Spain2 sites
Novartis Investigative Site
Barcelona, Catalonia, 08035
Novartis Investigative Site
Madrid, 28040
About this study
Official 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
This clinical study will assess the doses of BKM120 appropriate for patients with newly diagnosed glioblastoma when given in combination with radiotherapy and temozolomide.
- Conditions
- Glioblastoma
- Being tested
- BKM120 + temozolomide, BKM120 +temozolomide with/without radiotherapy
- Keywords
- BKM120, temozolomide, glioblastoma multiforme, GBM, Newly diagnosed
- Medical subject headings
- Glioblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BKM120 + temozolomideDrug
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.
BKM120 +temozolomide with/without radiotherapyDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| BKM120 + Temozolomide (Concomitant Phase) | Experimental | 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 Receives: Drug: BKM120 + temozolomide |
| BKM120 + temozolomide with/without radiotherapy | Experimental | 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 Receives: Drug: BKM120 +temozolomide with/without radiotherapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Dose Limiting Toxicity (DLT)
Per DLT criteria as defined in protocol
Measured: Concomitant phase (42 days), adjuvant phase cycle 1 (28-day cycle), adjuvant phase cycles 2 (28-day cycle)
Secondary outcomes (5)
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)
Measured: Baseline, 30 days post the last BKM120 treatment
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.
Measured: Baseline, 18 months after first BKM120 treatment
Progression free survival (PFS)
Per patient survival follow up feedbacks
Measured: at 12 months and at 18 months
Overall survival (OS)
Per patient survival follow up feedbacks
Measured: Until death or consent withdrawal
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.
Measured: 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)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Nov 2011 (estimated)
- Study start30 Dec 2011
- Primary completion17 May 2017
- Study completion17 May 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for GlioblastomaStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 38 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01473901
- Sponsor's protocol ID
- CBKM120E2101
- Other IDs
- 2011-001157-87
- Status last verified
- Sep 2017
- First submitted
- 18 Aug 2011
- Last updated
- 9 Dec 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Wen PY, Rodon JA, Mason W, Beck JT, DeGroot J, Donnet V, Mills D, El-Hashimy M, Rosenthal M. Phase I, open-label, multicentre study of buparlisib in combination with temozolomide or with concomitant radiation therapy and temozolomide in patients with newly diagnosed glioblastoma. ESMO Open. 2020 Jul;5(4):e000673. doi: 10.1136/esmoopen-2020-000673.
PubMed 32661186
Study at a glance
From the registry record, last updated by the sponsor on 9 Dec 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official 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
- ClinicalTrials.gov ID
- NCT01473901
- Acronym / sponsor ID
- CBKM120E2101
- Conditions
- Glioblastoma
- Keywords
- BKM120, temozolomide, glioblastoma multiforme, GBM, Newly diagnosed
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 38 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 30 Dec 2011 (actual)
- Primary completion
- 17 May 2017 (actual)
- Study completion
- 17 May 2017 (actual)
- First posted
- 17 Nov 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This clinical study will assess the doses of BKM120 appropriate for patients with newly diagnosed glioblastoma when given in combination with radiotherapy and temozolomide.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| BKM120 + Temozolomide (Concomitant Phase) | Experimental | Drug: BKM120 + temozolomideCranial 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 |
| BKM120 + temozolomide with/without radiotherapy | Experimental | Drug: BKM120 +temozolomide with/without radiotherapyAdjuvant 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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:
- Patient is able to be assessed by periodic dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) scan
- Patient has Karnofsky performance status >= 60
Key exclusion criteria (13 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BKM120 + temozolomideThe 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. | Drug | BKM120 + Temozolomide (Concomitant Phase) |
| BKM120 +temozolomide with/without radiotherapyThe 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. | Drug | BKM120 + temozolomide with/without radiotherapy |
Primary outcome
Dose Limiting Toxicity (DLT)
Time frame: Concomitant phase (42 days), adjuvant phase cycle 1 (28-day cycle), adjuvant phase cycles 2 (28-day cycle)
Per DLT criteria as defined in protocol
5 secondary outcomes
No of participants with Adverse events based on abnormal laboratory results, abnormal electrocardiogram (ECG) findings
Time frame: Baseline, 30 days post the last BKM120 treatment
Objective response rate (ORR)
Time frame: Baseline, 18 months after first BKM120 treatment
Progression free survival (PFS)
Time frame: at 12 months and at 18 months
Overall survival (OS)
Time frame: Until death or consent withdrawal
Plasma concentration-time profiles and basic pharmacokinetic parameters of BKM120 and temozolomide (Cmax, tmas, AUC, half-life)
Time frame: 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)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Dec 2020.
- Derived from this study: PubMed 32661186Wen PY, Rodon JA, Mason W, Beck JT, DeGroot J, Donnet V, Mills D, El-Hashimy M, Rosenthal M. Phase I, open-label, multicentre study of buparlisib in combination with temozolomide or with concomitant radiation therapy and temozolomide in patients with newly diagnosed glioblastoma. ESMO Open. 2020 Jul;5(4):e000673. doi: 10.1136/esmoopen-2020-000673.
- Results for CBKM120E2101 can be found on the Novartis Clinical Trial Results WebsiteLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
8 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing BKM120 + temozolomide and BKM120 +temozolomide with/without radiotherapy in people with Glioblastoma, run by Novartis Pharmaceuticals at 8 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Dec 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in United States, Canada, Spain, Australia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Dose Limiting Toxicity (DLT) (time frame: Concomitant phase (42 days), adjuvant phase cycle 1 (28-day cycle), adjuvant phase cycles 2 (28-day cycle)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01473901, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Dec 2020.