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Phase I-II Study With Tumor Molecular Pharmacodynamic (MPD) Evaluation and Pharmacokinetics of PD-0332991 in Patients Suffering Metastatic Melanoma

Information source: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov processed this data on August 20, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Melanoma BRAF V600E/K Mutated; CDNKN2A Loss Defined

Intervention: PD- 0332991 (Drug)

Phase: Phase 1/Phase 2

Status: Recruiting

Sponsored by: Assistance Publique - Hôpitaux de Paris

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 with BR. The main objective is to establish the Maximum Tolerated Dose (MTD) of PD-0332991 when added to standard vemurafenib therapy (960 mg BID). The estimated MTD is defined as the dose of PD-0332991 combined with vemurafenib that will be associated with a prespecified proportion of patients experiencing a Dose-Limiting Toxicity (DLT), ie, 1/3.

Clinical Details

Official title: An Open Label Multicenter, Phase I-II Study With Tumor Molecular Pharmacodynamic (MPD) Evaluation and Pharmacokinetics of PD-0332991 in Patients Suffering Metastatic Melanoma With BRAFv600 Mutated and CDKN2A Loss and Expression of Rb and Treated by Vemurafenib

Study design: Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: Occurrence within the first 2 cycles of treatment of a DLT

Secondary outcome:

Efficacy

1 year survival rate

Tolerance

Eligibility

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria:

- 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 Criteria:

- 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

Locations and Contacts

Saint-Louis Hospital, Paris 75010, France; Recruiting
Celeste Lebbe, MDPHD, Phone: +33 1 42 49 49 49, Email: celeste.lebbe@sls.aphp.fr
celeste lebbe, MD-PHD, Principal Investigator
Additional Information

Starting date: May 2014
Last updated: March 17, 2015

Page last updated: August 20, 2015

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