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

Completed · Phase 2

Conditions studied: Non Small Cell Lung Cancer

In brief

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.

Key facts

Study ID

NCT01487265

Run by

SCRI Development Innovations, LLC

People needed

37

Starts

2014-03-01

Expected to finish

2017-12-11

Last updated by the study team

2019-03-06

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• 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.

You may not qualify if…

• 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 ideation, or homicidal ideation (immediate risk of doing harm to others)
• ≥ Grade 3 anxiety
• Meets the cut-off score of ≥10 12 in the Patient Health Questionnaire (PHQ-9) or a cut-off of ≥15 in the Generalized Anxiety Disorder Assessment (GAD-7) mood scale, respectively, or selects a positive response of "1, 2, or 3" to question number 9 regarding potential for suicidal thoughts in the PHQ-9 (independent of the total score of the PHQ-9) will be excluded from the study.
• Active cardiac disease including any of the following:
• Angina pectoris that requires the use of anti-anginal medication
• Ventricular arrhythmias except for benign premature ventricular contractions
• Supraventricular and nodal arrhythmias requiring a pacemaker or not controlled with medication
• Conduction abnormality requiring a pacemaker
• Valvular disease with documented compromise in cardiac function
• Symptomatic pericarditis
• Uncontrolled hypertension
• History of cardiac dysfunction including any of the following:
• Myocardial infarction within the last 6 months
• History of documented congestive heart failure (New York Heart Association functional classification III-IV) within the last 6 months
• Documented cardiomyopathy
• Stroke or transient ischemic attack within the past 6 months
• Poorly controlled diabetes mellitus (HbA1c >8%)
• Currently taking therapeutic doses of warfarin sodium or any other coumadin-derivative anticoagulant. Therapy with low molecular weight heparin (LMWH), rivaroxaban, or fondaparinux is allowed.
• Other concurrent severe and/or uncontrolled concomitant medical conditions (e.g., active or uncontrolled infection) that could cause unacceptable safety risks or compromise compliance with the protocol

Where it is running

• Florida Cancer Specialists South — Fort Myers, Florida, United States
• Florida Hospital Cancer Institute — Orlando, Florida, United States
• Florida Cancer Specialists North — St. Petersburg, Florida, United States
• Florida Cancer Specialists East — West Palm Beach, Florida, United States
• Oncology Hematology Care, Inc. — Cincinnati, Ohio, United States
• Tennessee Oncology, PLLC — Nashville, Tennessee, United States
• Center for Cancer and Blood Disorders — Fort Worth, Texas, United States

Full record on ClinicalTrials.gov

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