Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Immune System Diseases

Lung Neoplasms

Carcinoma, Non-Small-Cell Lung

Hypersensitivity

Carcinoma

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Antineoplastic Agents

All Drugs and Chemicals

Amino Acids

Erlotinib Hydrochloride

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

Cycle 1: BKM120 80 mg PO daily; Erlotinib 100mg PO daily

Cycles 2 and beyond: BKM120 100 mg PO daily; Erlotinib 100mg PO daily

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.

BKM120 and Erlotinib

David R Spigel, MD

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 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 benefitting from the treatment, has no evidence of disease progression, and does not meet any criteria for discontinuation or withdrawal.

Trial of Erlotinib and BKM120 in Patients With Advanced Non Small Cell Lung Cancer Previously Sensitive to Erlotinib

Phase II Trial of Erlotinib and BKM120 in Patients With Advanced Non Small Cell Lung Cancer Previously Sensitive to Erlotinib

Percentage of patients who are alive and progression-free at 3 months (APF3) from first treatment.

Defined as the time from first treatment until death from any cause.

Defined as the time from complete or partial response (CR or PR) until objective tumor progression. Tumor measurements will be obtained using CT scans of chest, abdomen and pelvis and assessed per RECIST v 1.1. Complete response (CR) is defined as a disappearance of all lesions; partial response (PR) is defined as at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking the baseline sum LD as reference. Stable Disease (SD) is defined as neither sufficient shrinkage to qualify for PR, nor sufficient increase to qualify for progressive disease, taking as reference the smallest (nadir) sum LD since start of treatment.

Defined as the percentage of complete and partial responses (CR + PR) among all patients. Complete response (CR) is defined as a disappearance of all lesions; partial response (PR) is defined as at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking the baseline sum LD as reference. Stable Disease (SD) is defined as neither sufficient shrinkage to qualify for PR, nor sufficient increase to qualify for progressive disease, taking as reference the smallest (nadir) sum LD since start of treatment.

Adverse events will be graded using CTCAE v4.3. and will be collected until 30 days after the discontinuation of study treatment for each participant. A non-serious adverse event is any untoward medical occurrence. A serious adverse event (SAE) is an event that meets one or more of the following: results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; requires intervention to prevent permanent impairment or damage. Specific AE and SAE terms are provided in the Adverse event module.

Novartis

SCRI Development Innovations, LLC

BKM120, administered 80 mg by mouth (PO) daily during the first week of Cycle 1, then escalated to 100 mg PO daily. Erlotinib, administered 100 mg PO daily. Each cycle is 28 days.

Erlotinib + BKM120

Age, Continuous

Sex: Female, Male

United States

Region of Enrollment

Smoking Status

Patients that have received at least one dose of study treatment

Charles H. Davis

Patients that were treated with at least one dose of study treatment

Progression Free Survival at 3 Months

Patients that received at least one dose of study treatment

Overall Survival

Of 37 participates that received study treatment, only two participants met the minimum criteria to be included (one censored, and the remaining one analyzed for duration of response)

Duration of Response

patients that received at least one dose of study treatment

Spots Global Cancer Trial Database for bkm120 and erlotinib