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

Inclusion Criteria

Patients must have recovered to Grade 1 or better from any adverse events (except alopecia) related to prior antineoplastic therapy before screening procedures are initiated.

• Patients with progressive NSCLC (any histology)
• Prior sensitivity to erlotinib or gefitinib or other EGFR TKI. Sensitivity is defined as follows:
• Patients treated with erlotinib (or gefitinib or other EGFR TKI) for any duration in the presence of a known EGFR activating mutation that confers sensitivity to TKI treatment. These include, but are not limited to mutations in L858R (Exon 21); Exon 19 deletion; G719S, G719A, G719C mutations (Exon 19);or L861Q (laboratory report required at enrollment).
• Prior treatment with erlotinib (or gefitinib, or other EGFR TKI), regardless of mutation status, where there was ≥6 months of disease control (no disease progression).
• At least one site of measurable disease as defined by RECIST criteria Version 1.1
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0 to 2
• Archival tumor tissue available for correlative testing (analysis of resistance mechanism to erlotinib).
• Failure of at least 1, and no more than 3, prior systemic treatments for advanced disease (either due to progressive disease or toxicity).
• Male or female ≥18 years of age.
• Patients may have received radiation for palliation prior to starting study drug if they have recovered from the side effects of such therapy. Time from last palliative radiation to beginning of study treatment should be ≥1 week. Patients may have received prior wide-field radiation prior to starting study drug if they have recovered from the side effects of such therapy. Time from last wide-field radiation to beginning of study treatment should be ≥2 weeks.
• Fasting plasma glucose (FPG) ≤120 mg/dL (6.7 mmol/L)
• Adequate hematologic, hepatic and renal function.
• Total calcium (corrected for serum albumin) WNL (bisphosphonate use for malignant hypercalcemia control is allowed)
• Magnesium ≥ the lower limit of normal (LLN)
• Potassium WNL for the institution
• Serum amylase and lipase ≤ ULN
• Ability to swallow oral medication
• Fertile males, defined as all males physiologically capable of conceiving offspring, must use condoms during treatment, and for an additional 24 weeks (6 months in total after study drug discontinuation), and should not father a child in this period.
• Female patients who are not of child-bearing potential, and female patients of child-bearing potential who agree to use adequate contraceptive measures, who are not breastfeeding, and who have a negative serum or urine pregnancy test performed within 48 hours prior to start of treatment.
• Willingness and ability to comply with study and follow-up procedures.
• Ability to understand the investigational nature of this study and give written informed consent.

Exclusion Criteria

• Prior treatment with a phosphatidylinositide 3-kinase (PI3K) inhibitor
• Known hypersensitivity to BKM120, and/or erlotinib/gefitinib
• Failure to recover to Grade 1 or better from any AEs (except alopecia) related to previous antineoplastic therapy before screening procedures are initiated.
• Untreated brain metastases. Patients with treated brain metastases may participate in this study, if the patient is ≥2 weeks from therapy completion (including radiation and/or surgery), has recovered from all effects of treatment, is clinically stable at the time of study entry, and is not receiving high-dose steroid therapy (patients on a low stable dose of steroids may be enrolled).
• Acute or chronic liver or renal disease or pancreatitis
• The following mood disorders, as judged by the Investigator or a Psychiatrist, or as a result of patient's mood assessment questionnaire:
• Medically documented history of active major depressive episode, bipolar disorder (I or II), obsessive-compulsive disorder, schizophrenia, a history of suicidal attempt or ide