This is a multi-center, open-label non-randomized dose-escalation trial of vorinostat given in combination with vinorelbine. Cohorts will be treated with a fixed dose of vinorelbine (25mg/m²/week continuously, representing the schedule that has been approved). Patients eligible will be enrolled into a standard 3+3 design with a starting dose of vorinostat at 200 mg po qd 7/21 (weekly schedule). Then, further dose levels will be explored. Toxicity of the schedule will be assessed during the first cycle. Patients may receive up to 6 cycles of study medication. Blood samples will be collected at specified time points to assess pharmacokinetic endpoints.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
30
Vorinostat will be administered orally at the starting dose of 200 mg po qd 7/21(weekly schedule) in combination with the standard dose of vinorelbine 25mg/m² per week as intravenous infusion over 10 minutes starting 4 hours after vorinostat administration. Barring dose limiting toxicities the dose of vorinostat will escalate in several steps (300 mg po qd 7/21 days, 300 mg po qd 21/21 days, 400 mg po qd 7/21 days, 400 mg po qd 21/21 days). Patients may receive a maximum of 6 cycles of study medication.
Centre René GAUDUCHEAU
Nantes Saint Herblain, France
Institut Curie
Paris, France
Institut Claudius REGAUD
Toulouse, France
To determine the maximum tolerated dose (MTD) of vorinostat administered in combination with standard doses of vinorelbine.
Time frame: at the end of the trial
To assess the pharmacokinetics of vorinostat and vinorelbine when administered in combination.
Time frame: at the end of the trial
To assess the safety and tolerability of this regimen in advanced solid tumors.
Time frame: at the end of the study
To make a preliminary assessment of the efficacy of the combination, in terms of response rate, response duration, time to response and time to progression.
Time frame: At the end of the trial
To evaluate predictive pharmacodynamic biomarkers (e.g., histone acetylation in peripheral blood) when vorinostat is administered in combination with vinorelbine.
Time frame: At the end of the trial
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