BKM120 Combined With Vemurafenib (PLX4032) in BRAFV600E/K Mutant Advanced Melanoma

Completed · Phase 1/Phase 2

Conditions studied: BRAF Mutant Metastatic Melanoma

In brief

This is a phase 1/2 clinical trial with the goal of determining whether the addition of the investigational agent BKM120 to vemurafenib will lead to improved 6-month progression-free survival in patients with BRAFV600E/K mutant melanoma.

Key facts

Study ID

NCT01512251

Run by

University of California, San Francisco

People needed

8

Starts

2012-06-09

Expected to finish

2017-03-21

Last updated by the study team

2020-08-17

Who can join

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

You may qualify if…

• Histologically or cytologically confirmed diagnosis of unresectable stage III and stage IV melanoma
• BRAFV600E or BRAFV600K mutation-positive
• Age >= 18 years
• Eastern Cooperative Oncology Group (ECOG) performance status <= 2
• Patients must have at least one site of measurable disease (per RECIST for solid tumors)
• Life expectancy of ≥ 12 weeks
• Adequate bone marrow function as shown by: Absolute Neutrophil Count (ANC) >= 1.5 x 109/L, Platelets >= 100 x 109/L, Hb >9 g/dL
• Total calcium (corrected for serum albumin) within normal limits (biphosphonate use for malignant hypercalcemia control is not allowed)
• Magnesium ≥ the lower limit of normal
• Potassium within normal limits for the institution
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) within normal range (or <= 3.0 x upper limit of normal (ULN) if liver metastases are present)
• Serum bilirubin within normal range (or <= 1.5 x ULN if liver metastases are present; or total bilirubin <= 3.0 x ULN with direct bilirubin within normal range in patients with well documented Gilbert Syndrome)
• Serum creatinine <= 1.5 x ULN or 24-hour clearance >= 50 mL/min
• Serum amylase <= ULN
• Serum lipase <= ULN
• International Normalized Ratio (INR) <= 2
• Fasting plasma glucose <= 120 mg/dL (6.7 mmol/L)
• Negative serum pregnancy test within 48 hours before starting study treatment

You may not qualify if…

• Patients who have received prior treatment with a PI3K inhibitor or a BRAF inhibitor, prior treatment with sorafenib is permitted.
• Patients with a known hypersensitivity to BKM120 or to its excipients
• Patients with untreated 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 (incl. radiation and/or surgery) and clinically stable at the time of study entry
• Patients with acute or chronic liver, renal disease or pancreatitis
• Patients with 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 or active major depressive episode, bipolar disorder (I or II), obsessive-compulsive disorder, schizophrenia, history of suicidal attempt or ideation, or homicidal ideation
• >= CTCAE grade 3 anxiety
• Meets the cut-off score of >= 10 in the Patient Health Questionnaire-9 (PHQ-9) or a cut-off of >= 15 in the General Anxiety Disorder-7 (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 unless overruled by the psychiatric assessment
• Patients with diarrhea >= CTCAE grade 2
• Patient has active cardiac disease including any of the following:
• Left ventricular ejection fraction (LVEF) < 50% as determined by multigated acquisition (MUGA) or echocardiogram (ECHO)
• QTc > 480 msec on screening ECG (using the QTcF formula)
• Personal or family history of prolonged QT syndrome
• 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
• Symptomatic pericarditis
• Patient has a history of cardiac dysfunction including any of the following:
• Myocardial infarction within the last 6 months, documented by persistent elevated cardiac enzymes or persistent regional wall abnormalities on assessment of left ventricular ejection fraction (LVEF) function
• History of documented congestive heart failure (New York Heart Association functional classification III-IV)
• Documented cardiomyopathy
• Poorly controlled diabetes mellitus (HbA1c > 8 %)
• Other concurrent severe and/or uncontrolled concomitant medical conditions that could cause unacceptable safety risks or compromise compliance with the protocol
• Significant symptomatic deterioration of lung function; if clinically indicated, pulmonary function tests including measures of predicted lung volumes, Diffusing capacity of the lungs for carbon monoxide (DLCO), oxygen (O2) saturation at rest on room air should be considered to exclude pneumonitis or pulmonary infiltrates

Where it is running

• University of California, San Francisco — San Francisco, California, United States

Full record on ClinicalTrials.gov

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