Phase 2
Completed N=31
Study of ADI-PEG 20 in Patients With Advanced Melanoma
Melanoma · Skin Cancer · Neoplasm
Source: ClinicalTrials.gov NCT00520299 ↗
Enrolled (actual)
31
Serious AEs
35.5%
Results posted
Apr 2017
Primary outcomePrimary: Assessment of Safety and Tolerability of ADI-PEG 20 — 6; 6; 19; 1 participants
Summary
This was a phase 1/2, open-label, dose-escalation study of arginine deiminase linked via succinimidyl succinate to polyethylene glycol of 20,000 molecular weight (ADI-PEG 20) in subjects with advanced melanoma. ADI-PEG 20 was administered intramuscularly (IM) at escalating doses weekly for 9 weeks (cycle 1) or 8 weeks (subsequent cycles). The primary objectives were to the establish the safety, tolerability, and clinical efficacy of ADI-PEG 20. Secondary objectives included evaluation of the metabolic activity by [18F]-fluorodeoxyglucose positron emission tomography (FDG PET), pharmacodynamics, correlation of immunogenicity with clinical response, and correlation of argininosuccinate synthetase (ASS) tumor expression with clinical response.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Assessment of Safety and Tolerability of ADI-PEG 20 |
6; 6; 19; 1; 2; 4 | — |
| PRIMARY Best Overall Clinical Tumor Response |
0; 0; 0; 3; 2; 4 | — |
| SECONDARY Metabolic Tumor Response |
1; 0; 6; 2; 3; 6 | — |
| SECONDARY Summary of ADI-PEG 20 Plasma Concentrations Over Time |
3.3; 4.4; 1.9; 35.5; 59.8; 57.2 | — |
| SECONDARY Summary of Plasma Arginine Levels Over Time |
55; 62; 49; 2; 9; 4 | — |
| SECONDARY Summary of Plasma Citrulline Levels Over Time |
38; 29; 23; 195; 158; 225 | — |
| SECONDARY Summary of ADI-PEG 20 Immunogenicity Over Time |
0.2; 0.2; 0.1; 0.2; 0.0; 0.4 | — |
| SECONDARY Correlation Between ASS Tumor Expression and Clinical Response |
2; 0; 3; 1; 1; 0 | — |
Eligibility Criteria
Inclusion Criteria
- Histologically confirmed malignant melanoma, American Joint Committee on Cancer (AJCC) stage III (unresectable) or IV. Subjects with uveal and mucosal melanomas were eligible.
- Measurable disease using the Response Evaluation Criteria in Solid Tumors (RECIST).
- Pathology slides reviewed by the Memorial Hospital Department of Pathology or New York University (NYU) Department of Pathology for confirmation of melanoma diagnosis.
- Karnofsky performance status of 80% or more.
- Adequate organ and marrow function, as defined below:
- white blood cell count ≥ 3000/µL
- absolute neutrophil count ≥ 1500/µL
- platelet count ≥ 100,000/µL
- total bilirubin ≤ 2.5 x institutional upper limit of normal (ULN)
- lactate dehydrogenase ≤ 1.5 x institutional ULN
- albumin ≥ 3.0 mg/dL
- creatinine ≤ 2.0 mg/dL
- Expected survival of at least 3 months.
- Age ≥ 18 years.
- Able and willing to give valid written informed consent.
Exclusion Criteria
- Receipt of chemotherapy, immunotherapy, or radiotherapy within 3 weeks prior to first dosing of study agent or lack of recovery from adverse events (AEs) due to agents administered more than 3 weeks earlier. For nitrosoureas, at least 6 weeks must have elapsed.
- Any other malignancy that required concomitant therapy.
- Any medical condition that could have made it difficult for the subject to complete the full course of treatments, at the discretion of the Principal Investigator or co-Principal Investigators.
- Metastatic disease to the central nervous system, unless treated and stable.
- Known human immunodeficiency virus (HIV) positivity.
- Mental impairment that may have compromised the ability to give informed consent and comply with the requirements of the study.
- Lack of availability for clinical follow-up assessments.
- Participation in any other clinical trial involving another investigational agent within 3 weeks prior to enrollment.
- Pregnant women or women who were nursing. Women of child-bearing potential and sexually active men must have used appropriate contraception during the course of this study. Women of child-bearing potential must not have been pregnant (negative β human chorionic gonadotropin within 2 weeks of treatment) or nursing during treatment.
- History of seizure disorder.
Data sourced from ClinicalTrials.gov (NCT00520299). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.