Phase I/II Study of ADI-SS PEG 20,000mw in Patients With Advanced Metastatic Melanoma
This is a phase I/II, open-label, dose-escalation study of ADI-SS PEG 20,000 mw in patients
with advanced melanoma. Eligible patients will receive ADI-SS PEG 20,000 mw intramuscularly
(IM) once weekly for 9 weeks (Cycle 1). [18F]-FDG PET and CT scans will be performed at
baseline and at the end of cycle 1 (week 8 and 9 respectively) for assessment of tumor
response and changes in tumor metabolic activity induced by ADI-SS PEG 20,000 mw. [18F]-FDG
PET will also be performed on study day 4 for assessment of tumor metabolic activity
following the first dose of ADI-SS PEG 20,000 mw. Formal assessment of response by RECIST
and EORTC functional criteria will be based on a comparison of conventional CT scans and
[18F]-FDG PET scans done pre-treatment and at the end of Cycle 1 (week 8 and 9).
Blood samples will be obtained prior to each ADI-SS PEG 20,000 mw IM injection for plasma
arginine and citrulline levels and ADI concentration analysis and detection of anti-ADI
antibodies. Patients will be assessed by physical examination and laboratory studies (CBC,
fibrinogen, PT/PTT, comprehensive chemistry panel, LDH, amylase, lipase and uric acid) every
two weeks while undergoing treatment. A review of toxicities will be conducted during each
If a patient completes treatment in Cycle 1 without Dose limiting toxicity (DLT, then the
patients will be eligible to continue to Cycle 2 starting at study week #10 if one of the
following criteria is met:
1. CT shows enlargement of existing disease without accompanying symptoms.
2. CT shows stable disease or improvement and there is no unacceptable toxicity.
If patient develops symptoms referable to disease progression or if CT shows new disease,
then no further ADI will be given.
Radiologic evaluations will be repeated for patients treated in Cycle 2 during study weeks
16 and 17 to determine eligibility for Cycle 3. The same eligibility criteria used for Cycle
2 will apply for continuation to Cycle 3.
The dose levels of ADI-SS PEG 20,000mw to be administered are outlined below:
- Cohort 1 (40 IU/m2)
- Cohort 2 (80 IU/m2)
- Cohort 3 (160 IU/m2)
The cohort determined to be the highest tolerated dose level from Phase I will be expanded
up to 25 patients.
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
To further establish the safety and tolerability of ADI- SS PEG 20,000 mw.
Jedd Wolchok, M.D., Ph.D.
Memorial Sloan-Kettering Cancer Center
United States: Food and Drug Administration
|Memorial Sloan-Kettering Cancer Center||New York, New York 10021|
|NYU Clinical Cancer Center||New York, New York 10016|