A Phase IA, multicenter, open-label dose escalation study of BKM120, administered orally in adult patients with advanced solid malignancies
- Conditions
- Advanced and/or metastatic cancer10027655
- Registration Number
- NL-OMON35139
- Lead Sponsor
- ovartis
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 19
1. Patients with advanced solid tumors who have progressed on standard therapy or for whom no standard anticancer therapy exists
2. At least one measurable or non-measurable lesion as defined by RECIST
3. Patients who fulfill the following criteria will be eligible for FDG-PET:
* tumor types known to have a high FDG uptake, such as breast, lung, GIST, melanoma, colorectal, lymphoma
* To be eligible for follow-up scans, patients should have FDG uptake with a tumor background ratio * 2 in at least one lesion * 2cm at baseline.
4. Availability of a representative tumor tissue specimen.
5. WHO Performance Status of * 2 and life expectancy of * 12 weeks
6. Patients must have the following laboratory values:
* Absolute Neutrophil Count * 1.5 x 109/L
* Hemoglobin * 9 g/dl <= 5.58 mmol/l
* Platelets * 100 x 109/L
* Potassium and totsal calcium within normal limits
* Magnesium * the lower limit of normal
* AST/SGOT and ALT/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
* Serum creatinine * 1.5 x ULN or 24-hour clearance * 50 mL/min
* Serum amylase and lipse * ULN
* Serum triglycerides * 500 mg/dL
* Fasting plasma glucose * 140 mg/dL (7.8 mmol/L)
7. Negative serum pregnancy test within 72 hours before starting study treatment
1. Presence of brain metastases. Exception for MTD part: Patients with treated brain metastases that are asymptomatic and have been clinically stable for 3 months
2. Prior treatment with a PI3K inhibitor
3. Presence of acute or chronic liver disease, renal disease or pancreatitis
4. Patients with any peripheral neuropathy * CTCAE grade 2
5. Patients with unresolved diarrhea * CTCAE grade 2
6. Impaired cardiac function or clinically significant cardiac diseases, including any of
the following: LVEF < 45%, ST depression or elevation of * 1.5 mm, congenital long QT syndrome and QTc > 480 msec, ventricular arrhythmias or atrial fibrillation, clinically significant bradycardia, complete left bundle branch block, right bundle branch block + left anterior hemiblock (bifascicular block), unstable angina pectoris or acute myocardial infarction * 3 months prior to studystart, congestive heart failure, uncontrolled hypertension.
7. Clinically manifest diabetes mellitus, history of gestational diabetes mellitus, or steroid-induced diabetes mellitus
8. Uncontrolled hypertriglyceridemia, active or uncontrolled infection
9. Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of BKM120
10. Treatment with any hematopoietic colony-stimulating growth factors * 2 weeks prior to starting study drug.
11 Treatment with medication that has the potential to prolong the QT interval or inducing Torsades de Pointes
12. Therapeutic doses of warfarin sodium (Coumadin®) - for the Netherlands acenocoumarol and fenprocoumon
13. Corticosteroids * 2 weeks prior to starting study drug;Amendment 4: patients with the following mood disorders as judged by the Investigator or a psychiatrist:
* 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
* * CTCAE grade 3 anxiety
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Phase I: to determine the MTD of BKM120 as a single agent, administered orally<br /><br>daily. Estimation of the MTD will be based upon the estimation of the<br /><br>probability of DLT in cycle 1.</p><br>
- Secondary Outcome Measures
Name Time Method <p>* Safety: Type, frequency and severity of adverse events (CTCAE Version 3.0)<br /><br>* Efficacy: In the dose-escalation arm response will be also assessed by RECIST.<br /><br>* Pharmacokinetics<br /><br>* PD: PET response, blood and tumor biomarkers at baseline and post-BKM120<br /><br>dosing.</p><br>