A Phase I Study of BKM120 and Everolimus in Advanced Solid Malignancies

NCT01470209 | Completed Phase 1 DMC

• 2 other identifiers: IRB00048549WCI1925-10
• Study Type: interventional
• Target: 43
• Locations: 1 country
• Sites: 1

Brief Summary

This study will assess the safety of combining two agents (everolimus and BKM120) for the treatment of advanced cancer arising from solid organ in patients who are no longer benefiting from or unable to withstand standard treatment of these conditions.

Conditions

Solid Tumors; Lung Cancer

Keywords

lung cancer with activated mTOR/PI3K pathway; alterations in PIK3CA, NF1, TSC1/TSC2, mTOR, KRAS, LKB1, PTEN

Outcome Measures

Primary Outcomes (1)

• Dose limiting toxicity

  i. Grade 4 hematologic toxicity (excluding anemia) lasting more than 7 days ii. Grade 3 anemia lasting more than 7 days or requiring blood transfusion iii. Grade 4 anemia iv. Grade ≥ 3 febrile neutropenia of any duration v. Grade ≥ 3 nausea and or vomiting lasting more than 72 hours in spite of standard supportive therapy vi. Grade ≥ 3 non-hematologic toxicity (excluding alopecia)

  During the first cycle of treatment; approximately 4 weeks

Secondary Outcomes (1)

• Clinical benefit rate

  During the entire duration of therapy estimated to be an average of 6 months for each patient

Study Arms (1)

Combination of BKM120 and everolimus

EXPERIMENTAL

Drug: BKM120; Drug: Everolimus

Interventions

BKM120 DRUG

BKM120 (20mg to 100mg) will be self-administered (by the patients themselves). The investigator will instruct the patient to take the study drug exactly as specified in the protocol. BKM120 will be administered on a continuous once daily dosing schedule. Patients should be instructed to take the dose of BKM120 daily in the morning, one hour after a light breakfast (morning meal) at approximately the same time each day. BKM120 should be taken with a glass of water and consumed over as short a time as possible. Patients should swallow the capsules as a whole and not chew them. Patients should continue to fast for 2 hours after the administration of each BKM120 dose.

Also known as: Buparlisib

Combination of BKM120 and everolimus

Everolimus DRUG

RAD001 will be self-administered (by the patients themselves). The investigator will instruct the patient to take the study drug exactly as specified in the protocol. RAD001 will be administered orally as once daily dose of 5mg or 10 mg (based on the dose cohort) continuously from study day 1 until progression of disease or unacceptable toxicity. Patients will be instructed to take RAD001 in the morning, at the same time each day.

Also known as: RAD001, Afinitor

Combination of BKM120 and everolimus

Eligibility Criteria

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

You may qualify if:

• Histologic or cytologic confirmation of a solid malignancy with established intolerance or refractoriness to standard therapies
• Age ≥ 18 years
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
• Patients must have at least one site of measurable disease (per Response Evaluation Criteria in Solid Tumors \[RECIST\] 1.1 criteria)
• Adequate organ function including:
• Bone marrow function as shown by: absolute neutrophil count (ANC) ≥ 1.5 x 10⁹/L, platelets ≥ 100 x 10⁹/L, Hb \>9 g/dL
• Electrolytes: Total calcium (corrected for serum albumin) within normal limits (ongoing requirement for bisphosphonate to control malignant hypercalcemia is not allowed but prophylactic use of bisphosphonate to prevent skeletal complication of bone metastasis is allowed); magnesium ≥ the lower limit of normal
• Liver function: aspartate aminotransferase (AST)/serum glutamate oxaloacetate transaminase (SGOT) and alanine aminotransferase (ALT)/serum glutamate pyruvate transaminase (SGPT) ≤ 2.5 x Upper Limit of Normal (ULN) or ≤ 5.0 x ULN if liver metastases are present; serum bilirubin ≤ 1.5 x ULN in patients with known Gilbert Syndrome, total bilirubin ≤ 3 x ULN, with direct bilirubin ≤ 1.5 x ULN
• Renal function: serum creatinine ≤ 1.5 x ULN or 24-hour clearance ≥ 50 mL/min or calculated glomerular filtration rate (GFR) of 60cc/ml using the formula of Cockroft and Gault
• Serum amylase ≤ ULN
• Serum lipase ≤ ULN
• Fasting plasma glucose ≤ 120 mg/dL (6.7 mmol/L)
• International normalized ratio (INR) ≤ 2
• Negative serum pregnancy test within 48 hours before starting study treatment in women with childbearing potential
• Ability and willingness to participate in the informed consent process and signing a copy of the informed consent form

You may not qualify if:

• Patients who have received prior treatment with a phosphatidylinositol 3-kinase (P13K) inhibitor or RAD001 (if discontinued for toxicity)
• Patients with a known hypersensitivity to BKM120, RAD001 (including other rapalogs) or their excipients
• Patients with untreated symptomatic brain metastases are excluded. However, patients with metastatic central nervous system (CNS) tumors may participate in this trial, if the patient is \> 4 weeks from therapy completion (including radiation and/or surgery), is clinically stable at the time of study entry and is not receiving corticosteroid therapy for the brain mets.
• Patients with acute or chronic liver, renal disease or pancreatitis
• Patients has any of the following mood disorders as judged by the Investigator or a Psychiatrist, or who meets the cut-off score of ≥ 12 the Patient Health Questionnaire-9 (PHQ-9) or a cut-off of ≥ 15 in the Generalized Anxiety Disorder-7 (GAD-7) mood scale, respectively, or selects a positive response of '1, 2, or 3' to questions number 9 regarding potential for suicidal thoughts in the PHQ-9 (independent of the total score of the PHQ-9) :
• Medically documented history of or 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) or patients with active severe personality disorders are not eligible. Note: for patients with psychotropic treatments ongoing at baseline, the dose and the schedule should not be modified within the previous 6 weeks prior to start of study drug.
• ≥ Common Toxicity Criteria for Adverse Effects (CTCAE) grade 3 anxiety
• Note: The psychiatric judgment overrules the mood assessment questionnaire result or the investigators judgment.
• Patient has active cardiac disease including any of the following:
• Left ventricular ejection fraction (LVEF) \< 50% as determined by Multiple Gated acquisition (MUGA) scan or echocardiogram (ECHO)
• Corrected QT interval (QTc) \> 480 msec on screening ECG (using the Fridericia's corrected QT interval \[QTcF\] formula)
• Angina pectoris that requires the use of anti-anginal medication
• Ventricular arrhythmias except for benign premature ventricular contractions
• Supraventricular and nodal arrythmias requiring a pacemaker or not controlled with medication
• Conduction abnormality requiring a pacemaker

Sponsors & Collaborators

• Emory University: lead
• Novartis Pharmaceuticals: collaborator

Study Sites (1)

Winship Cancer Institute of Emory University

Atlanta, Georgia, 30322, United States

Location

Related Links

• Clinical Trials at Winship
• Winship Cancer Institute of Emory University

MeSH Terms

Conditions

Lung Neoplasms; Hereditary Sensory and Autonomic Neuropathies

Interventions

NVP-BKM120; Everolimus

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Nervous System Malformations; Nervous System Diseases; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Polyneuropathies; Peripheral Nervous System Diseases; Neuromuscular Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, Inborn

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals

Study Officials

• Taofeek Owonikoko, MD, PhD

  Emory University Winship Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor and Principal Investigator

Study Record Dates

• First Submitted: October 25, 2011
• First Posted: November 11, 2011
• Study Start: January 1, 2012
• Primary Completion: May 1, 2017
• Study Completion: May 1, 2017
• Last Updated: March 19, 2018

Record last verified: 2018-03

Locations

US (1)