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

Completed · Phase 1

Conditions studied: Solid Tumors, Lung Cancer

In brief

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.

Key facts

Study ID

NCT01470209

Run by

Emory University

People needed

43

Starts

2012-01-01

Expected to finish

2017-05-01

Last updated by the study team

2018-03-19

Who can join

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

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
• Presence of appropriate size and site of viable tumor tissue for safe tumor biopsy collection (the biopsy is optional and requirement is only applicable to subjects considered for the expansion cohort stage of the study)
• Ability and willingness to undergo repeat tumor biopsies (the biopsy is optional and only applicable to subjects considered for the expansion cohort stage of the study)

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
• Valvular disease with document compromise in cardiac function
• Symptomatic pericarditis
• Patient has a history of cardiac dysfunction including any of the following:
• Myocardial infraction within the last 6 months, documented by persistent elevated cardiac enzymes or preexistent regional wall abnormalities on assessment of LVEF function
• History of or documented congestive heart failure (New York Heart Association functional classification III-IV)
• Documented cardiomyopathy
• Active diarrhea ≥ CTCAE grade 2
• Patients with clinical manifestation of uncontrolled diabetes mellitus (i.e. treated and/or with clinical signs) or steroid-induced diabetes mellitus
• Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of BKM120 (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection). Patients with unresolved diarrhea will be excluded as previously indicated.
• Patients who have been treated with any hematopoietic colony-stimulating growth factors (e.g., granulocyte-colony stimulating factor [G-CSF], granulocyte macrophage-colony-stimulating factor [GM-CSF]) ≤ 2 weeks prior to starting study drug. Erythropoietin or darbepoetin therapy, if initiated at least 2 weeks prior to enrollment, may be continued.

Where it is running

• Winship Cancer Institute of Emory University — Atlanta, Georgia, United States

Full record on ClinicalTrials.gov

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