Clinical study with BKM120 (Buparlisib) for metastatic melanoma patients with brain metastases which are not eligible for surgery or radiosurgery
- Conditions
- metastatic melanoma with brain metastasesTherapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2013-003306-45-DE
- Lead Sponsor
- niversitätsklinikum Tübingen
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 22
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 <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’s Syndrome, which is defined as presence of
several episodes of unconjugated hyperbilirubinemia with normal results from CBC count (including normal
reticulocyte count and blood smear), normal liver function test results, and absence of other contributing disease
processes at the time of diagnosis
h.AST (SGOT) and ALT (SGPT) below or equal upper limit of normal range or (= 3.0 x ULN if liver metastases are
present)
i.Fasting plasma glucose (FPG) = 120mg/dL or = 6.7 mmol/L
j.HbA1c = 8%
3.Patient is able to swallow and retain oral medication
4.Patient must be at least 18 years old
5.Patient must have an estimated life expectancy > 8 weeks in the opinion of the investigator
6.Patient must have ECOG performance status < 2
Nature of illness and treatment history
7.Histologically confirmed diagnosis of melanoma
8.Patient must has shown evidence for PD in the brain by MRI without leptomeningeal disease
9.Contrast enhanced brain MRI and CT for chest / abdomen / pelvis or MRI for abdomen / pelvis must be performed
within 28 days before first dose of study treatment
10.Patient is able to be assessed by periodic MRI and CT scan
11.Patients BRAF V600 wildtype:
-must have objective evidence of progressive disease during or
-following treatment with Checkpoint-inhibitors for advanced melanoma
12.Patients BRAF V600 mutation positive:
-must have objective evidence of progression of disease during or
-following treatment with a BRAF inhibitor
-not be eligible for surgery or radiosurgery
13.Time interval between last day of previous anti-tumour local or systemic treatment and first dose of buparlisib:
-14 days elapsed from last treatment with surgery or radiosurgery
-28 days elapsed from last treatment with whole brain radiation
-28 days have elapsed from last dose of approved or investigational chemo-, cytokine-, immune-, biological-, or vaccine-therapy
14.Participants must have recovered to a grade 0 or 1 from the toxic effects of prior therapy
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 14
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range 8
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 < 6 months prior to enrolment
c.unstable angina pectoris
d.serious uncontrolled cardiac arrhythmia
e.Symptomatic pericarditis
f.QTcF > 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
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method