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Phase I/II Study of ADI-SS PEG 20,000mw in Patients With Advanced Metastatic Melanoma

Phase 1/Phase 2
18 Years
Not Enrolling
Metastatic Melanoma, Skin Cancer, Neoplasm

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Trial Information

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
study visit.

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.

Phase I:

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)

Phase II:

The cohort determined to be the highest tolerated dose level from Phase I will be expanded
up to 25 patients.

Inclusion Criteria:

1. Patients must have histologically confirmed malignant melanoma, AJCC stage III
(unresectable) or IV. Patients with uveal and mucosal melanomas are eligible.

2. Measurable disease using RECIST criteria (Appendix 1).

3. For all patients, pathology slides must be reviewed by the Memorial Hospital
Department of Pathology or NYU Department of Pathology for confirmation of melanoma

4. Patients must have a Karnofsky performance status of at least 80.

5. Patients must have adequate organ and marrow function as defined below:

- WBC >3,000/microL

- absolute neutrophil count >1,500/microL

- platelets >100,000/microL

- total bilirubin < 2.5X upper normal institutional limits

- LDH <1.5 X upper normal institutional limits

- albumin >3.0 mg/dl

- creatinine <2.0 mg/dl

6. Expected survival of at least 3 months.

7. Age ≥ 18 years.

8. Able and willing to give valid written informed consent.

Exclusion Criteria:

1. Patients who have had chemotherapy, immunotherapy or radiotherapy within 3 weeks
prior to first dosing of study agent or those who have not recovered from adverse
events due to agents administered more than 3 weeks earlier. For nitrosoureas, at
last six weeks must have elapsed.

2. Any other malignancy that requires concomitant therapy.

3. Any medical condition which might make it difficult for the patient to complete the
full course of treatments is grounds for exclusion, at the discretion of the
Principal Investigator or co-Principal Investigators.

4. Metastatic disease to the central nervous system, unless treated and stable.

5. Known HIV positivity.

6. Mental impairment that may compromise the ability to give informed consent and comply
with the requirements of the study.

7. Lack of availability for clinical follow-up assessments.

8. Participation in any other clinical trial involving another investigational agent
within 3 weeks prior to enrollment.

9. Pregnant women or women who are nursing are not eligible. Women of child-bearing
potential and sexually active men must be using appropriate contraception during the
course of this study. Women of child-bearing potential must not be pregnant (negative
beta HCG within 2 weeks of treatment) nor be nursing during treatment.

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

To further establish the safety and tolerability of ADI- SS PEG 20,000 mw.

Principal Investigator

Jedd Wolchok, M.D., Ph.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

Memorial Sloan-Kettering Cancer Center


United States: Food and Drug Administration

Study ID:




Start Date:

July 2007

Completion Date:

March 2010

Related Keywords:

  • Metastatic Melanoma
  • Skin Cancer
  • Neoplasm
  • metastatic melanoma
  • ADI
  • ADI PEG 20
  • ADI SS PEG 20,000mw
  • arginine
  • enzyme therapy
  • Neoplasms
  • Skin Neoplasms
  • Melanoma



Memorial Sloan-Kettering Cancer CenterNew York, New York  10021
NYU Clinical Cancer CenterNew York, New York  10016