Status:
UNKNOWN
Phase I-II Study With Tumor Molecular Pharmacodynamic (MPD) Evaluation and Pharmacokinetics of PD-0332991 in Patients Suffering Metastatic Melanoma
Lead Sponsor:
Assistance Publique - Hôpitaux de Paris
Conditions:
Melanoma BRAF V600E/K Mutated
CDNKN2A Loss Defined
Eligibility:
All Genders
18+ years
Phase:
PHASE1
PHASE2
Brief Summary
An open label multicentre, phase I-II study with tumour molecular pharmacodynamics (MPD) evaluation and pharmacokinetics of PD-0332991 added to vemurafenib in patients suffering metastatic melanoma wi...
Eligibility Criteria
Inclusion
- Age \> 18 years
- Stage IV or un-resectable stage III melanoma
- Presence of BRAF V600E/K mutation and CDNKN2A loss and expression of Rb using immunohistochemistry in a recent metastatic sample (\< 6 months)
- A previous exposure to BRAF inhibitor or combination of BRAF and MEK inhibitors therapy is allowed unless it has been stopped more than 3 months before study enrolment(This will defined the two strata of the trial)
- No previous therapy by MEK inhibitor unless associated with BRAF inhibitors
- No previous therapy with the AKT/PI3K pathway inhibitor
- Patients should have a tumour available for repeated biopsies for pharmacodynamics evaluation
- Life expectancy of \> 3 months
- ECOG performance status \<2
- Signed informed consent
- Patient with health insurance coverage
- No patient under guardianship or curators
Exclusion
- Inadequate hepatic function defined as serum bilirubin\>25 μmol/l, transaminases \> 3.0 times the upper limit of normal (ULN) or 5ULN in cases of liver metastases;
- Inadequate bone marrow function defined as absolute neutrophil count\<1500/mcl, platelets\<150000/mcl and haemoglobin\<8g/dL
- Inadequate renal function with serum creatinine\>2.0mg/dl) and /or creatinine clearance\< 60 ml/min
- Untreated brain metastases : Patients with brain metastases will be eligible if they have completed treatment 1 months prior to the start of study medication, have discontinued corticosteroid treatment for these metastases for at least 5 days, and are neurologically asymptomatic
- Myocardial infarct or unstable angina within the past 6 months
- Concomitant take of drugs known to be strong inhibitor or inducers of CYP314
- HIV positive.
- Chemotherapy, immunotherapy within 4 weeks
- Drugs interfering with PD-0332991 and vemurafenib metabolism
- Malabsorption syndrome or other condition that would interfere with enteral absorption
- Congenital long QT syndrome or screening QTc \> 470 msec
- Need for chronic corticosteroid therapy of ≥10 mg of prednisone per day
Key Trial Info
Start Date :
May 1 2014
Trial Type :
INTERVENTIONAL
Allocation :
ESTIMATED
End Date :
August 1 2018
Estimated Enrollment :
40 Patients enrolled
Trial Details
Trial ID
NCT02202200
Start Date
May 1 2014
End Date
August 1 2018
Last Update
April 18 2016
Active Locations (1)
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1
Saint-Louis Hospital
Paris, Paris, France, 75010