Trial of Erlotinib and BKM120 in Patients With Advanced Non Small Cell Lung Cancer Previously Sensitive to Erlotinib
Preclinical data in lung cancer cell lines showed that EGFR mutation can potentially be a positive predictor for sensitivity to BKM120. Furthermore, when the erlotinib-resistant model H1975 (LR858 and T790M mutation) was treated with BKM120, significant tumor control was observed (Novartis internal data). Therefore, combining BKM120 with erlotinib could potentially down-modulate PI3K-Akt activity resulting in a synergistic effect on cell growth inhibition and enhancing the response to erlotinib. This is multicentered, open-label, non-randomized Phase II study of BKM 120 and erlotinib in patients with advanced NSCLC previously sensitive to erlotinib.
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase II Trial of Erlotinib and BKM120 in Patients With Advanced Non Small Cell Lung Cancer Previously Sensitive to Erlotinib|
- Progression Free Survival (PFS) [ Time Frame: 24 months ] [ Designated as safety issue: No ]Evaluate the percentage of patients who are alive and progression-free at 3 months (APF3) from first treatment with the BKM120/erlotinib combination in patients with advanced NSCLC, previously sensitive to erlotinib.
- Evaluate toxicity of the BKM120/erlotinib combination using CTCAE v4.0. [ Time Frame: 24 months ] [ Designated as safety issue: Yes ]Efficacy data will be analyzed and summarized on an intent-to-treat (ITT) basis. The ITT population will consist of all patients enrolled. Safety data will be analyzed and summarized on a modified intent-to-treat (mITT) basis. The mITT population will consist of all patients in the ITT population and receiving at least one dose of study treatment. If more than 5 patients are enrolled but never receive study treatment, then efficacy data will also be analyzed and summarized on the mITT population.
- Assess anti-tumor activity [ Time Frame: 18 months ] [ Designated as safety issue: No ]Assess antitumor activity of this combination in terms of objective response rate (ORR), duration of response (DOR) and progression free survival (PFS).
- Correlate specific tumor biomarkers with treatment efficacy (exploratory) [ Time Frame: 24 months ] [ Designated as safety issue: No ]Exploratory correlative analyses are to include assessments of EGFR mutation (Exons 18-21 [including L858R], L861Q, Exon 19 deletion, T790M), K-ras mutation, MET amplification, molecular status of PIK3CA (gene mutation, Exons 9 and 20) and PTEN (gene mutation, Exons 1-9, and protein expression by IHC).
|Study Start Date:||May 2014|
|Estimated Study Completion Date:||October 2015|
|Estimated Primary Completion Date:||April 2015 (Final data collection date for primary outcome measure)|
Experimental: BKM120 and Erlotinib
Cycle 1: BKM120 80 mg PO daily; Erlotinib 100mg PO daily
Cycles 2 and beyond: BKM120 100 mg PO daily; Erlotinib 100mg PO daily
Drug: BKM120 and Erlotinib
BKM120 and Erlotinib will be given once daily. Erlotinib 100 mg PO will be administered. During Cycle 1-Week 1 all patients will receive 80 mg PO daily BKM120. After the first week of Cycle 1, the dose of BKM120 will escalate to 100 mg PO daily and treatment will continue as long as there are no unexpected or prohibitive toxicities, or disease progression.
Other Name: Buparlisib (BKM 120) and Tarceva (erlotinib)
This is a multicentered, open-label, non-randomized Phase II study of BKM120 and erlotinib in patients with advanced NSCLC previously sensitive to erlotinib. After six patients are enrolled and complete one treatment cycle a safety analysis of adverse events (AEs) will be conducted to assure there are no unexpected or prohibitive toxicities of the combination. The planned study enrollment will continue to up to 37 patients. Duration of a patient's participation in the study will vary. Treatment will continue as long as the patient is benefiting from the treatment, has no evidence of disease progression, and does not meet any criteria for discontinuation or withdrawal.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01487265
|Contact: David Spigel, MDfirstname.lastname@example.org|
|Contact: Trial Infoemail@example.com|
|United States, Florida|
|Florida Cancer Specialists North||Recruiting|
|Ft. Myers, Florida, United States, 33916|
|Florida Cancer Specialists South||Recruiting|
|Ft. Myers, Florida, United States, 33916|
|United States, Ohio|
|Oncology Hematology Cre, Inc.||Recruiting|
|Cincinnati, Ohio, United States, 45242|
|United States, Tennessee|
|Tennessee Oncology, PLLC||Recruiting|
|Nashville, Tennessee, United States, 37023|
|Principal Investigator: David Spigel, MD|
|United States, Texas|
|Center for Cancer and Blood Disorders||Recruiting|
|Fort Worth, Texas, United States, 76104|
|Study Chair:||David R Spigel, MD||SCRI Development Innovations, LLC|