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NCT01833169: SIGNATURE

BKM120 for Patients With PI3K-activated Tumors

Completed Phase 2 Results posted Last updated 19 October 2018
What this trial tests

Phase 2 trial testing BKM120 in PI3K Pathway Activated Tumors in 146 participants. Completed in 26 September 2016.

Timeline
29 March 2013
Primary endpoint
26 September 2016
26 September 2016

Quick facts

Lead sponsorNovartis Pharmaceuticals
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationna
Designsingle group
Maskingnone
Primary purposetreatment
Enrollment146
Start date29 March 2013
Primary completion26 September 2016
Estimated completion26 September 2016
Sites59 locations across United States

Drugs / interventions tested

Conditions studied

Sponsor

Novartis Pharmaceuticals — full company profile →

Who can join

Adults 18 to 100, any sex, with PI3K Pathway Activated Tumors. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Participant Clinical Benefit Response Rate Primary · Week 16

Clinical benefit rate for patients with solid tumors will be assessed using RECIST 1.1 and will include responses of Complete Response (CR) or Partial Response (PR) or Stable Disease (SD) at \>=16 weeks. For hematologic tumors other appropriate hematological response criteria was applied. Response criteria: CR=Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm., PR=At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters, SD=Neither sufficient shri

GroupValue95% CI
BKM12015.19.7 – 21.9
Overall Response of Partial Response (PR) or Greater. PR=at Least a 30% Decrease in the Sum of Diameters of Target Lesions, Taking as Reference the Baseline Sum Diameters Secondary · baseline and every 8 weeks until disease progression or end of treatment, assessed up to 24 months

Overall Response (OR) of Partial Response (PR) or greater is based on local investigator assessment. For patients with solid tumors, the assessment criteria will be RECIST 1.1 and will include responses of CR and/or PR. For hematologic tumors other appropriate hematological response criteria apply

GroupValue95% CI
BKM1201.40.2 – 4.9
Progression-Free Survival - Number of Participants With an Event Secondary · Every 8 Weeks until death, assessed up to 24 months

Progression free survival (PFS) is defined as the time from the date of first dose to the date of first documented disease progression or relapse or death due to any cause

participants with an event
GroupValue95% CI
BKM120112
participants censored
GroupValue95% CI
BKM12034
Progression-Free Survival (PFS)- Kaplan-Meier Estimates of PFS Timing in Months Secondary · baseline up to 24 months

Progression free survival (PFS) is defined as the time from the date of first dose to the date of first documented disease progression or relapse or death due to any cause

GroupValue95% CI
BKM1201.91.8 – 2.34
Progression-Free Survival (PFS)- Kaplan-Meier Estimates of PFS Rate in Percentages Secondary · baseline up to 24 months

Progression free survival (PFS) is defined as the time from the date of first dose to the date of first documented disease progression or relapse or death due to any cause.

1 month
GroupValue95% CI
BKM12088.481.5 – 92.9
2 months
GroupValue95% CI
BKM12043.834.9 – 52.3
3 months
GroupValue95% CI
BKM12039.430.7 – 47.9
4 months
GroupValue95% CI
BKM12020.413.5 – 28.3
5 months
GroupValue95% CI
BKM12020.413.5 – 28.3
6 months
GroupValue95% CI
BKM12014.18.2 – 21.5
9 months
GroupValue95% CI
BKM1205.82.1 – 12.1
12 months
GroupValue95% CI
BKM1202.90.6 – 8.6
Overall Survival - Number of Participants With an Event Secondary · Every 8 Weeks until death, assessed up to 24 months

Overall survival (OS) is defined as the time from the date of first dose to the date of death due to any cause. If a patient is not known to have died, survival time will be censored at the date of the last contact

participants with an event
GroupValue95% CI
BKM120110
participants censored
GroupValue95% CI
BKM12036
Overall Survival (OS)- Kaplan-Meier Estimates of OS Timing in Months Secondary · baseline up to 24 months

Overall survival (OS) is defined as the time from the date of first dose to the date of death due to any cause. If a patient is not known to have died, survival time will be censored at the date of the last contact

GroupValue95% CI
BKM1206.35.2 – 8.8
Overall Survival (OS)- Kaplan-Meier Estimates of OS Rate in Percentages Secondary · baseline up to 30 months

Overall survival (OS) is defined as the time from the date of first dose to the date of death due to any cause. If a patient is not known to have died, survival time will be censored at the date of the last contact

1 month
GroupValue95% CI
BKM12097.392.8 – 99.0
2 months
GroupValue95% CI
BKM12083.476.2 – 88.5
3 months
GroupValue95% CI
BKM12073.565.5 – 80.0
4 months
GroupValue95% CI
BKM12061.553.0 – 68.9
5 months
GroupValue95% CI
BKM12060.151.6 – 67.6
6 months
GroupValue95% CI
BKM12051.543.0 – 59.4
9 months
GroupValue95% CI
BKM12041.333.2 – 49.3
12 months
GroupValue95% CI
BKM12030.222.6 – 38.1

Adverse events — posted to ClinicalTrials.gov

Time frame: Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Treatment Last Visit (LPLV). All AEs reported I this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 30 months.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

BKM120
Serious: 59/146 (40%)
Deaths:

Serious adverse events (89 terms)

ReactionSystemBKM120
Abdominal painGastrointestinal disorders
VomitingGastrointestinal disorders
NauseaGastrointestinal disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
PneumoniaInfections and infestations
DehydrationMetabolism and nutrition disorders
Mental status changesPsychiatric disorders
LeukocytosisBlood and lymphatic system disorders
Small intestinal obstructionGastrointestinal disorders
PyrexiaGeneral disorders
SepsisInfections and infestations
Failure to thriveMetabolism and nutrition disorders
HydronephrosisRenal and urinary disorders
HypoxiaRespiratory, thoracic and mediastinal disorders
AnaemiaBlood and lymphatic system disorders
Abdominal pain lowerGastrointestinal disorders
Intestinal obstructionGastrointestinal disorders
PainGeneral disorders
Liver abscessInfections and infestations
Urinary tract infectionInfections and infestations
HyperglycaemiaMetabolism and nutrition disorders
SeizureNervous system disorders
SyncopeNervous system disorders
Confusional statePsychiatric disorders
Respiratory failureRespiratory, thoracic and mediastinal disorders
Other adverse events (43 terms — click to expand)

ReactionSystemBKM120
FatigueGeneral disorders
NauseaGastrointestinal disorders
Decreased appetiteMetabolism and nutrition disorders
DiarrhoeaGastrointestinal disorders
AnxietyPsychiatric disorders
DepressionPsychiatric disorders
VomitingGastrointestinal disorders
HyperglycaemiaMetabolism and nutrition disorders
Aspartate aminotransferase increasedInvestigations
Weight decreasedInvestigations
Alanine aminotransferase increasedInvestigations
RashSkin and subcutaneous tissue disorders
ConstipationGastrointestinal disorders
InsomniaPsychiatric disorders
CoughRespiratory, thoracic and mediastinal disorders
DehydrationMetabolism and nutrition disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
AnaemiaBlood and lymphatic system disorders
Abdominal painGastrointestinal disorders
DysgeusiaNervous system disorders
DyspepsiaGastrointestinal disorders
Oedema peripheralGeneral disorders
DizzinessNervous system disorders
HeadacheNervous system disorders
Urinary tract infectionInfections and infestations
Blood bilirubin increasedInvestigations
HypomagnesaemiaMetabolism and nutrition disorders
Back painMusculoskeletal and connective tissue disorders
Confusional statePsychiatric disorders
Mucosal inflammationGeneral disorders
Abdominal pain upperGastrointestinal disorders
Blood alkaline phosphatase increasedInvestigations
HypokalaemiaMetabolism and nutrition disorders
HyponatraemiaMetabolism and nutrition disorders
Muscular weaknessMusculoskeletal and connective tissue disorders
TremorNervous system disorders
Dry skinSkin and subcutaneous tissue disorders
PruritusSkin and subcutaneous tissue disorders
Dry mouthGastrointestinal disorders
Gamma-glutamyltransferase increasedInvestigations

Most-reported serious reactions: Abdominal pain, Vomiting, Nausea, Dyspnoea, Pneumonia, Dehydration, Mental status changes, Leukocytosis.

Data from ClinicalTrials.gov NCT01833169 adverse events section.

Sponsor's own description

The purpose of this signal seeking study was is to determine whether treatment with BKM120 demonstrates sufficient efficacy in select pathway-activated solid tumors and/or hematologic malignancies to warrant further study.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Role of PI3K/AKT pathway in cancer: the framework of malignant behavior.
    Jiang N, Dai Q, Su X, Fu J, et al · · 2020 · cited 419× · PMID 32333246 · DOI 10.1007/s11033-020-05435-1
  2. PI3K Inhibitors in Cancer: Clinical Implications and Adverse Effects.
    Mishra R, Patel H, Alanazi S, Kilroy MK, et al · · 2021 · cited 207× · PMID 33801659 · DOI 10.3390/ijms22073464
  3. Precision Oncology Medicine: The Clinical Relevance of Patient-Specific Biomarkers Used to Optimize Cancer Treatment.
    Schmidt KT, Chau CH, Price DK, Figg WD. · · 2016 · cited 84× · PMID 27197880 · DOI 10.1002/jcph.765
  4. Targeting the PI3K/AKT/mTOR pathway in epithelial ovarian cancer, therapeutic treatment options for platinum-resistant ovarian cancer.
    Rinne N, Christie EL, Ardasheva A, Kwok CH, et al · · 2021 · cited 80× · PMID 35582310 · DOI 10.20517/cdr.2021.05
  5. Next-Generation Sequencing to Guide Clinical Trials.
    Siu LL, Conley BA, Boerner S, LoRusso PM. · · 2015 · cited 51× · PMID 26473189 · DOI 10.1158/1078-0432.ccr-14-3215
  6. Proteomic landscape of epithelial ovarian cancer.
    Qian L, Zhu J, Xue Z, Zhou Y, et al · · 2024 · cited 33× · PMID 39085232 · DOI 10.1038/s41467-024-50786-z
  7. Signature program: a platform of basket trials.
    Slosberg ED, Kang BP, Peguero J, Taylor M, et al · · 2018 · cited 33× · PMID 29765547 · DOI 10.18632/oncotarget.25109
  8. Cotargeting mTORC and EGFR Signaling as a Therapeutic Strategy in HNSCC.
    Swick AD, Prabakaran PJ, Miller MC, Javaid AM, et al · · 2017 · cited 30× · PMID 28446642 · DOI 10.1158/1535-7163.mct-17-0115

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Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT01833169.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing