metastatic melanoma with brain metastases
Conditions
Interventions
Product Name: Buparlisib
Product Code: BKM120
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Buparlisib
CAS Number: 913611-97-9
Other descriptive name: BUPARLISIB
Concentration unit: mg mill
Sponsors
Universitätsklinikum Tübingen
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Patients eligible for inclusion in this study have to meet all of the following criteria: 1. Patient has signed the Informed Consent (ICF) prior to any screening procedures being performed and is able to comply with protocol requirements. 2. Patient has adequate bone marrow and organ function as defined by the following laboratory values; (Clinical labs – performed within 14 days prior to enrollment) Hematology a. Absolute Neutrophil Count (ANC) = 1.0 x 109/L b. Platelet count = 100 x 109/L (For patients with hematologic malignancies involving the bone marrow, platelet count > 75 x 109/L) c. Hemoglobin = 9.0 g/dL Coagulation d. INR = 1.5 Biochemistry e. Potassium and calcium (corrected for albumin), within normal limits for the institution, or = Grade 1 if judged not clinically significant by the investigator f. Serum creatinine = 1.5 x ULN and/or creatinine clearance > 50% LLN (Lower Limit of Normal) g. Total Serum bilirubin = ULN (or 8 weeks in the opinion of the investigator 6. Patient must have ECOG performance status =65 years) no F.1.3.1 Number of subjects for this age range 8
Exclusion criteria
Exclusion criteria: 1. Patient has a known hypersensitivity to any of the excipients of buparlisib 2. Patient who has received wide field radiotherapy = 4 weeks or limited field radiation for palliation = 2 weeks prior to starting study drug or who have not recovered to Grade 1 or better from related side effects of such therapy (except alopecia) 3. Patient has not recovered to Grade 1 or better (except alopecia) from related side effects of any prior antineoplastic therapy 4. Patient has had major surgery within 14 days prior to starting study drug or has not recovered from major side effects 5. Patient is currently receiving increasing or chronic treatment (> 5 days) with corticosteroids or another immunosuppressive agent a. The following uses of corticosteroids are permitted: single doses; e.g. with standard premedication for taxanes; topical applications (e.g., rash), inhaled sprays (e.g., obstructive airways diseases), eye drops or local injections b. Patient taking an enzyme-inducing anti-epileptic drug (EIAED): phenobarbital, phenytoin, fosphenytoin, primidone, rufinamide carbamazepine, oxcarbazepine, eslicarbazepine, felbamate, and topiramate (only when daily dose exceeds 200 mg). Participant must be off any EIAEDs for at least two weeks prior to starting study c. Requirement of more than 4 mg dexamethasone daily 6. Patient is being treated at start of study treatment with any of the following drugs: a. Drugs known to be strong inhibitors or inducers of isoenzyme CYP3A including herbal medications. b. Drugs with a known risk to induce Torsades de Pointes (List of prohibited QT prolonging drugs c. Note: The patient must have discontinued strong inducers for at least one week and must have discontinued strong inhibitors before the treatment is initiated. Switching to a different medication prior to starting study treatment is allowed. d. Patient who has received prior treatment with a PI3K inhibitor, AKT inhibitor or mTOR inhibitor e. Patient who have received anti-angiogenic or anti-VEGF targeted agents 7. Patient is currently receiving warfarin or any other coumarin-derivative anticoagulant for treatment, prophylaxis or otherwise. Therapy with heparin, low molecular weight heparin (LMWH), or fondaparinux is allowed 8. Patient who has who have other concurrent severe and/or uncontrolled medical conditions that would, in the investigator’s judgment, contraindicate patient participation in the clinical study (e.g., active or uncontrolled severe infection, chronic active hepatitis, immuno-compromised, acute or chronic pancreatitis, uncontrolled high blood pressure, interstitial lung disease, etc.) 9. Patient has a known history of human immunodeficiency virus (HIV) infection (testing not mandatory) 10. Patient has any of the following cardiac abnormalities: a. symptomatic congestive heart failure b. Myocardial infarction 480 msec on the screening ECG (using the QTcF formula) g. Currently receiving treatment with medication that has a known risk to prolong the QT interval or inducing Torsades de Pointes, and the treatment cannot be discontinued or switched to a different medication prior to starting study drug. 11. Patient has impairment of gastrointestinal (GI) function or GI disease that may significant
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of the study is to assess the intracranial disease control rate (IC-DCR), defined as the proportion of patients with confirmed complete intracranial responses (CR), partial intracranial responses (PR) or stable intracranial disease (SD) assessed by investigators in patients with melanoma-derived brain metastases treated with oral buparlisib. ;Secondary Objective: The secondary objectives of the study is to • estimate the overall response rate (ORR) • estimate duration of response of intracranial disease and OR • estimate progression-free survival (PFS) • estimate overall survival (OS) • to characterize the safety and tolerability of buparlisib throughout the study ;Primary end point(s): The primary endpoint of this study is the intracranial disease control rate (IC-DCR), which is defined as the percentage of patients whose intracranial response is a confirmed complete response (CR), partial response (PR) or stable disease (SD) assessed by investigators using modified RECIST 1.1 criteria.;Timepoint(s) of evaluation of this end point: Week 4, 8 and every week 8 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The secondary endpoints of this study are: • Overall response rate, defined as the percentage of patients with a confirmed investigator-assessed overall CR, PR using RECIST 1.1 criteria • Duration of response for the subsets of patients with confirmed intracranial CR or, PR defined as the time from first documented evidence of intracranial CR or PR until time of first documented intracranial disease progression or death due to any cause • Progression Free Survival (PFS), defined as the interval between the date of the first dose of study treatment and the earliest date of intracranial or extra- cranial disease progression or death due to any cause • Overall survival (OS), defined as the time from first dose of study treatment until death due to any cause • The safety endpoint of this study is the assessment of safety and tolerability of buparlisib, as measured by the nature and events, clinically significant laboratory abnormalities, vital signs, ECG, ECHO and clinical monitoring/observation. ;Timepoint(s) of evaluation of this end point: weeks, 4, 8 and every 8 weeks, safety parameter every 4 weeks | — |
Countries
Germany
Contacts
Public ContactProf. Dr.med. Claus Garbe
Skin Cancer Program Department of Dermatology
Outcome results
None listed