A Study of ADH-1 in Combination With Normothermic Isolated Limb Infusion of Melphalan

Study Overview
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Brief Summary
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N-cadherin, a protein involved in blood vessel cell binding and on the surface of many tumor cells, is increased as cancer progresses. ADH-1 blocks N-cadherin. This study will test the safety and effects of the combination ADH-1 with Normothermic Isolated Limb Infusion of Melphalan in subjects with locally advanced malignant melanoma.

Official Title
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An Open-Label, Multicenter, Phase 1/2 Dose Escalation Study to Evaluate Safety, Tolerability and Anti-tumor Activity of Systemic ADH-1 in Combination With Normothermic Isolated Limb Infusion of Melphalan in Subjects With Locally Advanced In-Transit Malignant Melanoma (Adherex Protocol Number AHX-01-007).

Conditions
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Neoplasms

Intervention / Treatment
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* Drug: ADH-1
* Drug: melphalan


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed written informed consent Male and female patients > or = 18 years of age with diagnosis of melanoma for which treatment with Normothermic Isolated Limb Infusion (ILI) of melphalan would be appropriate Measurable disease Disease site(s) must be distal to the planned site of tourniquet placement Available for immunohistochemical testing of N-cadherin expression tumor tissue Adequate performance status and organ function, as evidenced by hematological and biochemical blood testing and ECG Exclusion Criteria: Receipt of ADH-1 prior to this clinical study (prior melphalan via ILI, is okay) Stage IV melanoma Chemotherapy, radiotherapy, or any other investigational drug within 4 weeks before study entry History of tumors that have shown clinically significant evidence of active bleeding within 12 weeks before study entry Stroke, major surgery, or other major tissue injury within 4 weeks before study entry Uncontrolled congestive heart failure, coronary artery disease, or life threatening arrhythmias; myocardial infarction within 12 months; significant electrocardiogram (ECG) abnormalities Allergic reaction to any therapeutic peptide or to melphalan

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: ADH-1|4 gm IV Days 1 and 8|
|Drug: melphalan|By Isolated Limb Infusion (ILI), Lower Extremity: 7.5 mg/L (Limb Volume), Day 1 or Upper Extremity: 10 mg/L (Limb Volume), Day 1|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To tabulate the Best Overall Response according to unconfirmed RECIST, modified for cutaneous lesions |  | By Week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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cancer, tumors, melanoma, anticarcinogenic agents, antineoplastic agents, cadherins, solid tumors