A Trial of Gefitinib in Combination With BKM120 in Patients With Advanced Non-Small Cell Lung Cancer, With Enrichment for Patients Whose Tumours Harbour Molecular Alterations of PI3K Pathway and Known to Overexpress EGFR (BKM120)
|ClinicalTrials.gov Identifier: NCT01570296|
Recruitment Status : Active, not recruiting
First Posted : April 4, 2012
Last Update Posted : February 5, 2018
|Condition or disease||Intervention/treatment||Phase|
|Non-Small Cell Lung Cancer Solid Tumors||Drug: Gefitinib and BKM120||Phase 1|
• The safety, tolerability and recommended phase 2 dose (RP2D) of the combination of gefitinib and BKM120 will be determined.
- The pharmacokinetic (PK) profile of gefitinib in combination with BKM120 will be determined.
- The preliminary anti-tumor activity of gefitinib in combination with BKM120 will be determined.
- The pharmacodynamic target modulation effects using a hair follicle assay will be determined.
- The role of circulating tumour cells as assessed by a microfluidic device will be analyzed and the genetic alterations implicated in lung cancer, including but not limited to EGFR mutations, PI3KCA mutations, PTEN loss will be characterized.
- The feasibility of detecting somatic mutations from plasma DNA will be ascertained.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||38 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase Ib Trial of Gefitinib (EGFR Tyrosine Kinase Inhibitor, Iressa™) in Combination With BKM120, an Oral Pan-class I PI3K Inhibitor in Patients With Advanced Non-Small Cell Lung Cancer, With Enrichment for Patients Whose Tumours Harbour Molecular Alterations of PI3K Pathway and Known to Overexpress EGFR|
|Actual Study Start Date :||October 3, 2011|
|Primary Completion Date :||February 22, 2016|
|Estimated Study Completion Date :||April 2018|
Experimental: Gefitinib and BKM120
Patients with NSCLC who progress on treatment with single-agent EGFR TKI (e.g., gefitinib or erlotinib), and meet the clinical definition of EGFR TKI resistance (Jackman et al., 2010):
Patients should have systemic progression of disease (by RECIST) while on continuous treatment with gefitinib or erlotinib. Patients that have previously progressed on EGFR TKI (not in the preceding line of treatment) may also be enrolled and will receive gefitinib and BKM120 sequentially.
Patients with any solid tumour-type and "activated" PI3 kinase pathway and historically known to over express EGFR may also be recruited.
Once the RP2D is reached, an expansion cohort of 40 patients will be accrued for extended safety experience and to ascertain preliminary activity.
Drug: Gefitinib and BKM120
Dose escalation study of gefitinib and BKM120 with expansion cohort
- Recommended phase 2 dose for gefitnib and BKM120 combination therapy [ Time Frame: 24 months ]
- Pharmacokinetic (PK) profile of BKM120 in combination with gefitinib. [ Time Frame: 22 time points up to 4 weeks ]
- Preliminary antitumor activity [ Time Frame: 24 months ]Using radiological imaging and RECIST criteria
- Number of Participants with Adverse Events as a Measure of Safety and Tolerability [ Time Frame: 24 months ]
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01570296
|National Cancer Centre Singapore|
|Singapore, Singapore, 169610|
|Principal Investigator:||Daniel SW Tan, BSc, MRCP||Early Clinical Research Unit, Medical Oncology, National Cancer Centre Singapore|