c-MET Inhibitor; PI3K Inhibitor, PTEN Mutations, Homozygous Del. of PTEN or PTEN Neg. by IHC, c-Met Ampli. by FISH, INC280, BKM120, Buparlisib; Recurrent GBMPhase 1/2NCT01870726

Safety and Efficacy of INC280 and Buparlisib (BKM120) in Patients With Recurrent Glioblastoma

A Phase 1/2 study testing INC280 and Buparlisib in people with c-MET Inhibitor; PI3K Inhibitor, PTEN Mutations, Homozygous Del. of PTEN or PTEN Neg. by IHC, c-Met Ampli. by FISH, INC280, BKM120, Buparlisib; Recurrent GBM, run by Novartis Pharmaceuticals at 13 sites in 5 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

Search all trials

Trial summary

The study assessed the safety and the dose of the combination of INC280 and buparlisib (BKM120), as well as the anti-tumor activity of the combination, in patients with recurrent glioblastoma with PTEN mutations, homozygous deletion of PTEN or PTEN negative by IHC. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: c-MET Inhibitor; PI3K Inhibitor, PTEN Mutations, Homozygous Del. of PTEN or PTEN Neg. by IHC, c-Met Ampli. by FISH, INC280, BKM120, Buparlisib; Recurrent GBM
What is being tested?: INC280 and Buparlisib
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 43 participants
Where: 13 sitesin 5 countries
Study dates: 9 Jan 2014to 23 Dec 2016
Phase: Phase 1/2
Are there results?: Yes, posted in the registrySummary in the doctors' view

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

≥ 18 years of age.
Histologically confirmed diagnosis of glioblastoma (after initial tumor resection or biopsy) with radiographic evidence of recurrent tumor per RANO criteria.
Phase Ib: Documented evidence of PTEN mutations, homozygous deletion of PTEN or PTEN negative (H Score <10) by IHC confirmed by local or central assessment.
Phase II: Documented evidence of c-Met amplification (GCN>5) (fusion transcripts or mutant c-Met may be eligible after discussion with Novartis) or PTEN mutations, homozygous deletion of PTEN or PTEN negative (H Score <10) by central assessment.
Must have received the following treatment for glioblastoma:
•Prior treatment with radiotherapy and temozolomide; Note: A maximum of two prior chemotherapy/antibody regimens (including bevacizumab or other direct VEFG/VEGFR inhibitors) for recurrent disease are permitted.

Show all 10Show fewer

Representative archival tumor sample from glioblastoma (formalin-fixed paraffine embedded tissue) must be available.
ECOG performance status ≤ 2.
Able to swallow and retain oral medication.
Patients in the surgical arm only: patients with recurrent glioblastoma must be eligible for surgical resection as deemed by the site Investigator.

Who cannot join

Prior or current treatment with a c-MET inhibitor or HGF-targeting therapy
Prior treatment with a PI3K and/or mTOR inhibitors for glioblastoma or for pre-existing neoplasm transformed to glioblastoma (applicable for combination treatment arm only)
Received radiation (including therapeutic radioisotopes such as strontium 89) therapy ≤ 3 months prior to the first dose of study treatment and have not recovered from side effects of such therapy (≤ Grade 1) prior to the first dose of study treatment, except for alopecia.
Receiving treatment with medications that are known strong inhibitors or inducers of CYP3A, and cannot be discontinued 7 days prior to the start of the treatment and during the course of the study.
Receiving treatment with medications that are known CYP3A, CYP1A2, CYP2C8, CYP2C9 or CYP2C19 substrates with narrow therapeutic index, and cannot be discontinued during the course of the study.
Receiving treatment with long acting proton pump inhibitors, and cannot be discontinued 3 days prior to the start of INC280 treatment and during the course of the study.

Show all 26Show fewer

Currently receiving warfarin or other coumadin-derived anticoagulants for treatment, prophylaxis or otherwise.
Currently receiving increasing or chronic treatment ( > 5 days) with corticosteroids (e.g. dexamethasone > 4 mg/day or other corticosteroids equivalent dose) or another immunosuppressive agent.
History of acute or chronic pancreatitis or any risk factors that may increase the risk of pancreatitis.
Active cardiac disease or a history of cardiac dysfunction.
Impairment of gastrointestinal (GI) function or GI disease that might significantly alter the absorption of study drug
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 (e.g. risk of doing harm to self or others), or patients with active severe personality disorders (defined according to DSM- IV).
Anxiety ≥ CTCAE grade 3
Any of the following baseline laboratory values:
Hemoglobin < 9 g/dL
Platelet count < 75 x 109/L
Absolute neutrophil count (ANC) < 1.0 x 109/L
INR > 1.5
Serum lipase > normal limits for the institution
Asymptomatic serum amylase > grade 2
Potassium, magnesium, and calcium (corrected for albumin) > normal limits for the institution
Total bilirubin > 1.5 x ULN
Serum creatinine >1.5 x ULN or creatinine clearance ≤ 45 mL/min
Alanine aminotransferase (AST) or aspartate aminotransferase (ALT) > 3.0 x ULN (or < 5.0 x ULN if liver metastases are present)
Fasting plasma glucose > 120mg/dL or > 6.7 mmol/L
HbA1c > 8%.

Trial locations and contacts

13 sites in 5 countries.

Country

City, postcode or hospital

13 sites in 5 countries

United States5 sites

Dana Farber Cancer Institute SC
Boston, Massachusetts, 02215
Duke University Medical Center Duke - Baker
Durham, North Carolina, 27710
University of Texas MD Anderson Cancer Center SC-3
Houston, Texas, 77030
Columbia University Medical Center- New York Presbyterian Dept of Oncology
New York, New York, 10032
Memorial Sloan Kettering Cancer Center Neurology
New York, New York, 90033

Other trials in United States

Germany3 sites

Novartis Investigative Site
Bonn, 53105
Novartis Investigative Site
Heidelberg, 69120
Novartis Investigative Site
Tübingen, 72076

Other trials in Germany

Netherlands2 sites

ErasmusMC Cancer Institute - Neurooncology, RM G3-55
Rotterdam, 3075EA
University Medical Center Utrecht, Rm Q05.4.300, P.O. Box 85500
Utrecht, 3508 GA

Other trials in Netherlands

Spain2 sites

Novartis Investigative Site
Barcelona, Catalonia, 08035
Novartis Investigative Site
Madrid, 28041

Other trials in Spain

Switzerland1 site

Novartis Investigative Site
Sankt Gallen, 9007

Other trials in Switzerland

About this study

Official title: A Phase Ib/II, Multi-center, Open-label Study of INC280 in Combination With Buparlisib in Patients With Recurrent Glioblastoma

Read the detailed description

This was a multi-center, open-label, phase Ib/II study. The aim of the phase Ib part was to estimate the MTD and/or to identify the recommended phase II dose (RP2D) for the combination of INC280 and buparlisib, followed by the phase II part to assess the clinical efficacy of INC280 single agent and in combination with buparlisib (BKM120), and to further assess the safety of the combination. In addition, a surgical arm should have started concurrently with the phase II part, to determine the PK/PD profile of the study drug combination in patients undergoing tumor resection for recurrent glioblastoma after 7 to 10-days treatment.

RP2D was not declared due to a lack of efficacy of the combination in the phase Ib stage, and phase II was continued with INC280 monotherapy only.

Conditions: c-MET Inhibitor; PI3K Inhibitor, PTEN Mutations, Homozygous Del. of PTEN or PTEN Neg. by IHC, c-Met Ampli. by FISH, INC280, BKM120, Buparlisib; Recurrent GBM
Being tested: INC280, Buparlisib
Keywords: Glioblastoma multiforme (GBM), glioblastoma, Grade IV Astrocytoma, brain tumor, brain cancer, giant cell glioblastoma, gliosarcoma
Medical subject headings: Glioblastoma, Brain Neoplasms, Gliosarcoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

INC280Drug
Phase Ib: INC280 was given at the starting dose of 200mg capsules twice daily with escalation to higher strengths.
Phase II: INC280 was given at the dose of 400mg (tablets) twice daily.
BuparlisibDrug
Also called BKM120
Buparlisib was given at the starting dose of 50mg once daily with escalation to higher strengths.

Study groups in NCT01870726
Study group	Role	What they receive
Phase Ib	Experimental	To estimate the safe dose of the combination INC280 and buparlisib Receives: Drug: INC280; Drug: Buparlisib
Phase II	Experimental	To estimate anti-tumor efficacy of INC280 single agent and in combination with buparlisib Receives: Drug: INC280

What is being measured

The primary outcome is the main question the study is designed to answer.

Number of Patients Reporting Dose Limiting Toxicities (DLTs) in Cycle 1
A DLT is defined as an adverse event or abnormal laboratory value where the relationship to study treatment cannot be ruled out, and is not primarily related to disease, disease progression, inter-current illness, or concomitant medications that occurs within the first cycle of treatment (28 days) with INC280 in combination with buparlisib and meets any of the pre-defined criteria. The maximum tolerated dose was identified as INC280 300 mg BID + buparlisib 80 mg QD.
Measured: Cycle 1, 28 days
Phase II: Progression Free Survival Rate (PFSR)
Estimated rate of patients treated during 6 months without experiencing disease progression.
The Progression Free Survival Rate at 6 months was to be estimated using a Bayesian model described in the protocol. The models operating characteristics were evaluated based on the enrollment of at least 30 patients enrolled. Patients did not reach the milestone for the PFSR analysis (trial terminated); as such no analysis was performed.
Measured: 6 months
Phase II Surgical Arm: Concentrations of INC280 and Buparlisib in Tumor.
Concentrations of INC280 and buparlisib in tumor tissue.
Measured: 7 days

Secondary outcomes (11)

Number of Participants With Adverse Events
To characterize the safety of INC280 single agent and in combination with buparlisib including type, frequency, severity of adverse events, serious adverse events, and dose interruptions and adjustments. Adverse events will be assessed according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03, unless otherwise specified.
If CTCAE grading did not exist for an AE, the severity of mild, moderate, severe, and lifethreatening, corresponding to Grades 1 - 4, were used. CTCAE Grade 5 (death) was not used in this study but was collected as a seriousness criterion; rather, information about deaths was collected though a Death form.
Measured: throughout the duration of the trial, approximately 3 years from FPFV to LPLV
Pharmacokinetic Profile of INC280 - AUCtau
Plasma concentration profile of INC280 in combination with Buparlisib. AUCtau is the AUC from time zero to the end of dosing interval.
Measured: Cycle 1 Day 1, Cycle 1 Day 15, and Cycle 2 Day 1, approximately 6 months
Pharmacokinetic Profile of INC280 - Cmax
Plasma concentration profile of INC280 in combination with Buparlisib. Cmax is the Maximum (peak) observed drug concentration after dose administration.
Measured: Cycle 1 Day 1, Cycle 1 Day 15, and Cycle 2 Day 1, approximately 6 months
Pharmacokinetic Profile of INC280 - Tmax
Plasma concentration profile of INC280 in combination with Buparlisib. Tmax is the time to reach maximum (peak) observed concentration (Cmax) after dose administration
Measured: Cycle 1 Day 1, Cycle 1 Day 15, and Cycle 2 Day 1, approximately 6 months
Pharmacokinetic Profile of INC280 - T1/2
Plasma concentration profile of INC280 in combination with Buparlisib. T1/2 is the terminal half life
Measured: Cycle 1 Day 1, Cycle 1 Day 15, and Cycle 2 Day 1, approximately 6 months
Pharmacokinetic Profile of Buparlisib - AUCtau
Plasma concentration profile of Buparlisib in combination with INC280. AUCtau is the AUC from time zero to the end of dosing interval.
Measured: Cycle 1 Day 1, Cycle 1 Day 15, and Cycle 2 Day 1, approximately 6 months
Pharmacokinetic Profile of Buparlisib - Cmax
Plasma concentration profile of INC280 in combination with Buparlisib. Cmax is the Maximum (peak) observed drug concentration after dose administration.
Measured: Cycle 1 Day 1, Cycle 1 Day 15, and Cycle 2 Day 1, approximately 6 months
Pharmacokinetic Profile of Buparlisib - Tmax
Plasma concentration profile of INC280 in combination with Buparlisib. Tmax is the time to reach maximum (peak) observed concentration (Cmax) after dose administration
Measured: Cycle 1 Day 1, Cycle 1 Day 15, and Cycle 2 Day 1, approximately 6 months
Pharmacokinetic Profile of Buparlisib - T1/2
Plasma concentration profile of INC280 in combination with Buparlisib. T1/2 is the terminal half life
Measured: Cycle 1 Day 1, Cycle 1 Day 15, and Cycle 2 Day 1, approximately 6 months
Best Overall Response (BOR)
Best Overall Response (BOR) observed in the study population of INC280 Single Agent and in Combination with Buparlisib. Responses will be assessed by the investigators following the RANO criteria with MRI or CT scans scheduled every 8 weeks.
Summary of the RANO response criteria: CR has no T1-Gd+ (enhancing lesion), stable or decrease T2/FLAIR (non-enhancing lesion), absence of new lesion, stable or improve in clinical status; PR has ≥50% decrease T1-Gd+ (enhancing lesion), stable or decrease T2/FLAIR (non-enhancing lesion), absence of new lesion, stable or improve in clinical status; SD has ≥50% decrease but <25% increase T1-Gd+ (enhancing lesion), stable or decrease T2/FLAIR (non-enhancing lesion), absence of new lesion, stable or improve in clinical status; PD has ≥25% increase in T1-Gd+ (enhancing lesion), increase T2/FLAIR (non-enhancing lesion), presence of new lesion, deterioration in clinical status.
Measured: throughout the duration of the trial - approximately 3 years (from FPFV to LPLV)
Overall Survival (OS)
Survival rate of patients from start of treatment to date of death due to any cause.
Patients did not reach the milestone for the survival data analysis (terminated early); as such no analysis was done.
Measured: throughout the duration of the trial - approximately 3 years (FPFV to LPLV)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

9 Jan 201423 Dec 2016

First posted6 Jun 2013 (estimated)
Study start9 Jan 2014
Primary completion23 Dec 2016
Study completion23 Dec 2016

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for c-MET Inhibitor; PI3K Inhibitor, PTEN Mutations, Homozygous Del. of PTEN or PTEN Neg. by IHC, c-Met Ampli. by FISH, INC280, BKM120, Buparlisib; Recurrent GBMStudies 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 1/2
Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Single group
Masking: None (open label)
Enrolment: 43 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01870726
Sponsor's protocol ID: CINC280X2204
Other IDs: 2013-000699-14
Status last verified: May 2018
First submitted: 3 Jun 2013
Last updated: 30 May 2018
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: Undecided: Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Publications

van den Bent M, Azaro A, De Vos F, Sepulveda J, Yung WKA, Wen PY, Lassman AB, Joerger M, Tabatabai G, Rodon J, Tiedt R, Zhao S, Kirsilae T, Cheng Y, Vicente S, Balbin OA, Zhang H, Wick W. A Phase Ib/II, open-label, multicenter study of INC280 (capmatinib) alone and in combination with buparlisib (BKM120) in adult patients with recurrent glioblastoma. J Neurooncol. 2020 Jan;146(1):79-89. doi: 10.1007/s11060-019-03337-2. Epub 2019 Nov 27.
PubMed 31776899

Study at a glance

From the registry record, last updated by the sponsor on 30 May 2018. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase Ib/II, Multi-center, Open-label Study of INC280 in Combination With Buparlisib in Patients With Recurrent Glioblastoma
ClinicalTrials.gov ID: NCT01870726
Acronym / sponsor ID: CINC280X2204
Conditions: c-MET Inhibitor; PI3K Inhibitor, PTEN Mutations, Homozygous Del. of PTEN or PTEN Neg. by IHC, c-Met Ampli. by FISH, INC280, BKM120, Buparlisib; Recurrent GBM
Keywords: Glioblastoma multiforme (GBM), glioblastoma, Grade IV Astrocytoma, brain tumor, brain cancer, giant cell glioblastoma, gliosarcoma
Phase: Phase 1/2
Study type: Interventional
Recruitment status: Terminated
Enrolment: 43 participants (actual)
Lead sponsor: Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
Study start: 9 Jan 2014 (actual)
Primary completion: 23 Dec 2016 (actual)
Study completion: 23 Dec 2016 (actual)
First posted: 6 Jun 2013 (estimated)
Results: Posted 24 May 2018

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

RP2D was not declared due to a lack of efficacy of the combination in the phase Ib stage, and phase II was continued with INC280 monotherapy only.

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Single group
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
Phase Ib	Experimental	Drug: INC280, Drug: BuparlisibTo estimate the safe dose of the combination INC280 and buparlisib
Phase II	Experimental	Drug: INC280To estimate anti-tumor efficacy of INC280 single agent and in combination with buparlisib

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (10 listed)

≥ 18 years of age.
Histologically confirmed diagnosis of glioblastoma (after initial tumor resection or biopsy) with radiographic evidence of recurrent tumor per RANO criteria.
Phase Ib: Documented evidence of PTEN mutations, homozygous deletion of PTEN or PTEN negative (H Score <10) by IHC confirmed by local or central assessment.
Phase II: Documented evidence of c-Met amplification (GCN>5) (fusion transcripts or mutant c-Met may be eligible after discussion with Novartis) or PTEN mutations, homozygous deletion of PTEN or PTEN negative (H Score <10) by central assessment.
Must have received the following treatment for glioblastoma:

Key exclusion criteria (26 listed)

Prior or current treatment with a c-MET inhibitor or HGF-targeting therapy
Prior treatment with a PI3K and/or mTOR inhibitors for glioblastoma or for pre-existing neoplasm transformed to glioblastoma (applicable for combination treatment arm only)
Received radiation (including therapeutic radioisotopes such as strontium 89) therapy ≤ 3 months prior to the first dose of study treatment and have not recovered from side effects of such therapy (≤ Grade 1) prior to the first dose of study treatment, except for alopecia.
Receiving treatment with medications that are known strong inhibitors or inducers of CYP3A, and cannot be discontinued 7 days prior to the start of the treatment and during the course of the study.
Receiving treatment with medications that are known CYP3A, CYP1A2, CYP2C8, CYP2C9 or CYP2C19 substrates with narrow therapeutic index, and cannot be discontinued during the course of the study.

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
INC280Phase Ib: INC280 was given at the starting dose of 200mg capsules twice daily with escalation to higher strengths. Phase II: INC280 was given at the dose of 400mg (tablets) twice daily.	Drug	Phase II, Phase Ib
BuparlisibAlso: BKM120Buparlisib was given at the starting dose of 50mg once daily with escalation to higher strengths.	Drug	Phase Ib

Primary outcome

Number of Patients Reporting Dose Limiting Toxicities (DLTs) in Cycle 1
Time frame: Cycle 1, 28 days
A DLT is defined as an adverse event or abnormal laboratory value where the relationship to study treatment cannot be ruled out, and is not primarily related to disease, disease progression, inter-current illness, or concomitant medications that occurs within the first cycle of treatment (28 days) with INC280 in combination with buparlisib and meets any of the pre-defined criteria. The maximum tolerated dose was identified as INC280 300 mg BID + buparlisib 80 mg QD.
Phase II: Progression Free Survival Rate (PFSR)
Time frame: 6 months
Estimated rate of patients treated during 6 months without experiencing disease progression. The Progression Free Survival Rate at 6 months was to be estimated using a Bayesian model described in the protocol. The models operating characteristics were evaluated based on the enrollment of at least 30 patients enrolled. Patients did not reach the milestone for the PFSR analysis (trial terminated); as such no analysis was performed.
Phase II Surgical Arm: Concentrations of INC280 and Buparlisib in Tumor.
Time frame: 7 days
Concentrations of INC280 and buparlisib in tumor tissue.

11 secondary outcomes

Number of Participants With Adverse Events
Time frame: throughout the duration of the trial, approximately 3 years from FPFV to LPLV
Pharmacokinetic Profile of INC280 - AUCtau
Time frame: Cycle 1 Day 1, Cycle 1 Day 15, and Cycle 2 Day 1, approximately 6 months
Pharmacokinetic Profile of INC280 - Cmax
Time frame: Cycle 1 Day 1, Cycle 1 Day 15, and Cycle 2 Day 1, approximately 6 months
Pharmacokinetic Profile of INC280 - Tmax
Time frame: Cycle 1 Day 1, Cycle 1 Day 15, and Cycle 2 Day 1, approximately 6 months
Pharmacokinetic Profile of INC280 - T1/2
Time frame: Cycle 1 Day 1, Cycle 1 Day 15, and Cycle 2 Day 1, approximately 6 months
Pharmacokinetic Profile of Buparlisib - AUCtau
Time frame: Cycle 1 Day 1, Cycle 1 Day 15, and Cycle 2 Day 1, approximately 6 months
Pharmacokinetic Profile of Buparlisib - Cmax
Time frame: Cycle 1 Day 1, Cycle 1 Day 15, and Cycle 2 Day 1, approximately 6 months
Pharmacokinetic Profile of Buparlisib - Tmax
Time frame: Cycle 1 Day 1, Cycle 1 Day 15, and Cycle 2 Day 1, approximately 6 months
Pharmacokinetic Profile of Buparlisib - T1/2
Time frame: Cycle 1 Day 1, Cycle 1 Day 15, and Cycle 2 Day 1, approximately 6 months
Best Overall Response (BOR)
Time frame: throughout the duration of the trial - approximately 3 years (from FPFV to LPLV)
Overall Survival (OS)
Time frame: throughout the duration of the trial - approximately 3 years (FPFV to LPLV)

Results and safety

Results posted to the registry on 24 May 2018, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
200 mg BID Cap+50 mg QD	5	0
400 mg BID Cap+50 mg QD	6	0
500 mg BID Cap+50 mg QD	4	0
500 mg BID Cap+80 mg QD	6	0
300 mg BID Tab +80 mg QD	7	0
400 mg BID Tab +80 mg QD	5	0
400 mg BID Tab	10	0

Primary outcome: Number of Patients Reporting Dose Limiting Toxicities (DLTs) in Cycle 1

Time frame: Cycle 1, 28 days. Number. Unit: Number of Patients

Measure	200 mg BID Cap+50 mg QD n = 4	400 mg BID Cap+50 mg QD n = 5	500 mg BID Cap+50 mg QD n = 4	500 mg BID Cap+80 mg QD n = 6	300 mg BID Tab +80 mg QD n = 7	400 mg BID Tab+80 mg QD n = 4
Personality Change	0 (1257.87)	1 (2291.80)	0 (2604.72)	0 (2702.56)	0 (2702.47)	0 (5627.79)
Nausea	0 (4045.6 to 10405.8)	0 (3069.8 to 13946.9)	0 (6276.0 to 31532.5)	0 (1940.8 to 3618.0)	1 (8606.0 to 16381.0)	0 (11576.1 to 17422.8)
Aspartate Aminotransferase Increased	0 (3880.4 to 7192.8)	0 (2655.6 to 2655.6)	0 (19903.7 to 27092.8)	0 (4793.3 to 14289.7)	0 (7002.3 to 12184.7)	2 (13051.1 to 13051.1)

Population analysed: Dose determining set (DDS) consisted of all patients from the SAS who either met the minimum exposure criterion and had sufficient safety evaluations during Cycle 1, or discontinued earlier due to DLT during Cycle 1.

Primary outcome: Phase II: Progression Free Survival Rate (PFSR)

Time frame: 6 months

Population analysed: Based on the phase I, a RP2D was not determined for the combination arm (Phase II combination arms were not opened). Patients did not reach the milestone needed for the PFSR analysis (at minimum the Bayesian model requires 30 patients) due to early termination, as such no analysis for PFSR was performed.

Primary outcome: Phase II Surgical Arm: Concentrations of INC280 and Buparlisib in Tumor.

Time frame: 7 days

Population analysed: Based on the phase I, a RP2D was not determined for the combination and the phase II combination arms were not opened.

11 secondary outcomes are reported in the full results.

Adverse events

Time frame: Treatment Emergent Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit, approximately 3 years.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
INC280 200 mg BID Tab	1 of 1 (100%)	0 of 1 (0%)	Not reported
200 mg BID Cap+50 mg QD	3 of 5 (60%)	5 of 5 (100%)	Not reported
400 mg BID Cap + 50 mg QD	2 of 6 (33.3%)	6 of 6 (100%)	Not reported
500 mg BID Cap+50 mg QD	3 of 4 (75%)	4 of 4 (100%)	Not reported
500 mg BID Cap+80 mg QD	3 of 6 (50%)	6 of 6 (100%)	Not reported
300 mg BID Tab+ 80 mg QD	3 of 7 (42.9%)	7 of 7 (100%)	Not reported
400 mg BID Tab+80 mg QD	4 of 5 (80%)	5 of 5 (100%)	Not reported
All Patients (Phase Ib)	18 of 33 (54.5%)	33 of 33 (100%)	Not reported
400 mg BID Tab	2 of 9 (22.2%)	9 of 9 (100%)	Not reported
All Patients (Phase II)	3 of 10 (30%)	9 of 10 (90%)	Not reported

Limitations and caveats (from the sponsor): At the end of Phase Ib, it was decided not to enroll patients in the two Phase II arms evaluating INC280 with buparlisib. The phase II INC280 single agent arm was halted before it reached target enrollment.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 30 May 2018.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 31776899van den Bent M, Azaro A, De Vos F, Sepulveda J, Yung WKA, Wen PY, Lassman AB, Joerger M, Tabatabai G, Rodon J, Tiedt R, Zhao S, Kirsilae T, Cheng Y, Vicente S, Balbin OA, Zhang H, Wick W. A Phase Ib/II, open-label, multicenter study of INC280 (capmatinib) alone and in combination with buparlisib (BKM120) in adult patients with recurrent glioblastoma. J Neurooncol. 2020 Jan;146(1):79-89. doi: 10.1007/s11060-019-03337-2. Epub 2019 Nov 27.
Individual participant dataSharing planned: Undecided. Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

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

13 sites in 5 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

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 10 inclusion and 26 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: stopped early, as of the sponsor's last update on 30 May 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 13 sites in United States, Germany, Netherlands, Spain, Switzerland. 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 combined 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.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 24 May 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Number of Patients Reporting Dose Limiting Toxicities (DLTs) in Cycle 1 (time frame: Cycle 1, 28 days). The study lists 3 primary outcomes in all. 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 NCT01870726, 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 30 May 2018.