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

NCT01487265 | Completed Phase 2 Results

• 1 other identifier: SCRI LUN 214
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 7

Brief Summary

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.

Conditions

Non Small Cell Lung Cancer

Keywords

Erlotinib; BKM120; NSCLC

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival at 3 Months

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

  3 months

Secondary Outcomes (4)

• Overall Survival

  every 3 months after study treatment, projected 24 months

• Duration of Response

  every 8 weeks for 12 months, then every 12 weeks thereafter, estimated 18 months

• Objective Response Rate

  every 8 weeks for 12 months, then every 12 weeks thereafter, estimated 18 months

• Number of Participants With Serious and Non-serious Adverse Events as a Measure of Safety.

  Every 2 weeks for 8 weeks, then every 8 weeks thereafter, estimated 24 months

Study Arms (1)

BKM120 and Erlotinib

EXPERIMENTAL

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

Interventions

BKM120 and Erlotinib DRUG

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.

Also known as: Buparlisib (BKM 120) and Tarceva (erlotinib)

BKM120 and Erlotinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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)

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

Sponsors & Collaborators

• SCRI Development Innovations, LLC: lead
• Novartis: collaborator

Study Sites (7)

Florida Cancer Specialists South

Fort Myers, Florida, 33916, United States

Location

Florida Hospital Cancer Institute

Orlando, Florida, 32804, United States

Location

Florida Cancer Specialists North

St. Petersburg, Florida, 33705, United States

Location

Florida Cancer Specialists East

West Palm Beach, Florida, 33401, United States

Location

Oncology Hematology Care, Inc.

Cincinnati, Ohio, 45242, United States

Location

Tennessee Oncology, PLLC

Nashville, Tennessee, 37023, United States

Location

Center for Cancer and Blood Disorders

Fort Worth, Texas, 76104, United States

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

NVP-BKM120; Erlotinib Hydrochloride

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Charles H. Davis
• Organization: Sarah Cannon Research Institute

charles.davis2@scri-innovations.com

615-524-4341

Study Officials

• David R Spigel, MD

  SCRI Development Innovations, LLC

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 1, 2011
• First Posted: December 7, 2011
• Study Start: March 1, 2014
• Primary Completion: May 31, 2016
• Study Completion: December 11, 2017
• Last Updated: March 6, 2019
• Results First Posted: December 13, 2017

Record last verified: 2019-02

Locations

US (7)