A Multi-Center Phase I Dose Escalation Trial to Evaluate Safety and Tolerability of Intra-Arterial Temozolomide for Patients With Advanced Extremity Melanoma Using Normothermic Isolated Limb Infusion
1. The primary objective of this study is to determine the safety profile of
intra-arterial temozolomide administration during Isolated Limb Infusion (ILI) by
defining the dose limiting toxicities associated with this treatment and to determine
the maximum tolerated dose of intra-arterial administration of temozolomide during ILI
that will be used in a phase II efficacy trial.
2. Population will include patients who have undergone a previous Melphalan based regional
therapy for which they did not respond optimally and present with persistent,
progressive, or recurrent disease. Study activities include tumor tissue sampling,
blood sampling, and subjects will undergo an Isolated Limb Infusion.
3. To define both response in-field (area of the limb below the tourniquet) and
out-of-field (any area outside the tourniquet) in patients treated with temozolomide
based ILI. Response in this trial will be defined by the RECIST criteria (CR, PR, SD,
PD at 12 weeks post ILI). A CR rate of 20% would be considered as preliminary evidence
of a promising approach in this group of patients that have had a previous melphalan
regional treatment. ILI with melphalan has a complete response rate of approximately
35% in naïve patients and 20% in patients who have previously received melphalan based
To assess if the proposed treatment has any effect on quality of life as measured by the
Functional Assessment of Cancer Therapy - Melanoma.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Safety Profile of intra-arterial temozolomide and maximum tolerated dose of temozolomide
To determine the safety profile of intra-arterial temozolomide administration during Isolated Limb Infusion (ILI) by defining the dose limiting (DLT) and non dose limiting toxicities associated with this treatment. To determine the maximum tolerated dose (MTD) for intra-arterial administration of temozolomide during ILI that will be used in a phase II efficacy trial.
Douglas S Tyler, MD
United States: Food and Drug Administration
|MD Anderson Cancer Center||Houston, Texas 77030-4096|
|Duke University Medical Center||Durham, North Carolina 27710|
|Moffitt Cancer Center||Tampa, Florida 33612|