Study of NY-ESO-1 ISCOMATRIX® in Patients With High-risk, Resected Melanoma

Study Overview
=================
Brief Summary
-----------------
The purpose of this trial is to assess whether treatment with NY-ESO-1 ISCOMATRIX® vaccine improves outcomes for people with Malignant Melanoma which has been removed, but is at high risk of relapse.

Detailed Description
-----------------
NY-ESO-1 protein is an immune target found in many cancers including melanoma. ISCOMATRIX® adjuvant enhances immune responses. This trial compares NY-ESO-1 ISCOMATRIX® vaccine with ISCOMATRIX® adjuvant alone to assess whether treatment with NY-ESO-1 ISCOMATRIX® vaccine improves outcomes for participants with Malignant Melanoma which has been removed, but is at high risk of recurrence. Eligible participants are randomly allocated to a treatment arm. Treatment involves four intramuscular (into a muscle) injections (1 injection every 4 weeks x 3, plus 1 injection at 6 months). Participants are assessed for recurrence of melanoma, safety and immune responses (by blood test) over the 18 month study period. Off study, their own doctor will follow them for melanoma recurrence and survival.

Official Title
-----------------
Randomized, Double-blind Phase II Trial of NY-ESO-1 ISCOMATRIX® Vaccine and ISCOMATRIX® Adjuvant Alone in Patients With Resected Stage Ilc, Illb, lIIc, or IV Malignant Melanoma

Conditions
-----------------
Melanoma

Intervention / Treatment
-----------------
* Biological: NY-ESO-1 ISCOMATRIX®
* Biological: ISCOMATRIX® adjuvant


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Histologically proven malignant melanoma. Tumor expression of NY-ESO-1 antigen by immunohistochemistry. Fully resected AJCC stage IIc, IIIb, IIIc or IV melanoma. Within six months of surgery for melanoma. Full recovery from surgery. No immunotherapy or systemic adjuvant therapy for melanoma since most recent relapse and/or resection. (Previous adjuvant therapy accepted providing patient relapsed and resected after this.) Age 18 years or older. Able to give written informed consent. Vital laboratory parameters within normal range, or protocol specified ranges. Exclusion Criteria: Other serious or significant illnesses. Resected cerebral metastases. Ocular melanoma. Other malignancy within last 3 years, except for treated non-melanoma skin cancer and cervical cancer in situ. Using immunosuppressive drugs. Anticoagulation. Known HIV positivity. Chemotherapy or radiation therapy in last four weeks (6 weeks for nitrosourea drugs). Not available for immunological and clinical follow-up assessments. Participation in prior clinical trial involving an investigational agent within last 4 weeks. Previous isolated limb perfusion (ILP). Pregnancy or breastfeeding. Refusal or inability to use effective means of contraception for women of childbearing potential. Mental impairment that may compromise ability to give informed consent and to comply with study requirements.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Vaccine<br>NY-ESO-1 ISCOMATRIX® vaccine | Biological: NY-ESO-1 ISCOMATRIX®<br>* 100 μg of NY-ESO-1 protein formulated with 120 μg of ISCOMATRIX® adjuvant. Each patient will receive four intramuscular injections of NY-ESO-1 ISCOMATRIX® vaccine. The first three doses will be given at four-week intervals, days 1, 29, and 57, (± 3 days of scheduled date). The fourth injection will be given at month 6 (day 183 ± 3 days).<br>|
| Placebo Comparator: Adjuvant Alone<br>ISCOMATRIX® adjuvant alone | Biological: ISCOMATRIX® adjuvant<br>* 120 μg of ISCOMATRIX® adjuvant Each patient will receive four intramuscular injections of ISCOMATRIX® adjuvant alone. The first three doses will be given at four-week intervals, days 1, 29, and 57, (± 3 days of scheduled date). The fourth injection will be given at month 6 (day 183 ± 3 days).<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of Relapse-free Survival at 18 Months | The number of patients who were alive and relapse free 18 months after starting therapy and the number of patients who relapsed or died within 18 months of starting therapy. Disease was assessed according to Response Evaluation Criteria in Solid Tumors (RECIST) as measured by CT. Disease progression or relapse was based on an increase of 20% or more in the sum of the longest diameter of target lesions, the appearance of any new lesion as confirmed by CT scan or death. | 18 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients With Treatment -Emergent Adverse Events (TEAEs) | Toxicity was graded in accordance with the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 3.0. Adverse events (AEs) were reported based on clinical laboratory tests, vital sign and weight measurements, physical examinations, performance status evaluations, electrocardiograms, magnetic resonance imaging, and any other medically indicated assessments, including subject interviews, from the time informed consent is signed through 18 months. AEs were considered to be treatment emergent (TEAE) if they occurred or worsened in severity after the first dose of study treatment. | 18 months | 
| Relapse-Free Survival During the Entire Period of Observation (up to 6 Years). | Disease was assessed according to Response Evaluation Criteria in Solid Tumors (RECIST) as measured by CT. Disease progression or relapse was based on an increase of 20% or more in the sum of the longest diameter of target lesions, the appearance of any new lesion as confirmed by CT scan or death. | through study completion; up to 6 years | 
| Overall Survival | Overall Survival measured during the entire Period of Observation (up to 6years). Overall survival was measured from start of treatment to the last follow-up or death. | through study completion; up to 6 years | 
| NY-ESO-1 Antibody Response at Baseline Reported on a Scale of 0 to 4 With 0 Being no or Minimal Antibody Response and 4 the Highest Antibody Response | NY-ESO-1-specific antibodies were measured by an enzyme-linked immunosorbent assay ( ELISA) method at baseline and on days 71, 197, 365 and end of study. The results are reported as antibodies to NY-ESO-1-specific Total IgG (reciprocal titer) and were scored on a scale of 0-4 with 0 being no or minimal antibody response (reciprocal titer of 0-100) and 4 a strong antibody response (reciprocal titer of >100,000). The number of patients with each antibody response level are tabulated at each timepoint. | Baseline | 
| NY-ESO-1 Antibody Response on Day 71 Reported on a Scale of 0 to 4 With 0 Being no or Minimal Antibody Response and 4 the Highest Antibody Response | NY-ESO-1-specific antibodies were measured by an enzyme-linked immunosorbent assay ( ELISA) method at baseline and on days 71, 197, 365 and end of study. The results are reported as antibodies to NY-ESO-1-specific Total IgG (reciprocal titer) and were scored on a scale of 0-4 with 0 being no or minimal antibody response (reciprocal titer of 0-100) and 4 a strong antibody response (reciprocal titer of >100,000). The number of patients with each antibody response level are tabulated at each timepoint. | Day 71 | 
| NY-ESO-1 Antibody Response on Day 197 Reported on a Scale of 0 to 4 With 0 Being no or Minimal Antibody Response and 4 the Highest Antibody Response | NY-ESO-1-specific antibodies were measured by an enzyme-linked immunosorbent assay ( ELISA) method at baseline and on days 71, 197, 365 and end of study. The results are reported as antibodies to NY-ESO-1-specific Total IgG (reciprocal titer) and were scored on a scale of 0-4 with 0 being no or minimal antibody response (reciprocal titer of 0-100) and 4 a strong antibody response (reciprocal titer of >100,000). The number of patients with each antibody response level are tabulated at each timepoint. | Day 197 | 
| NY-ESO-1 Antibody Response on Day 365 Reported on a Scale of 0 to 4 With 0 Being no or Minimal Antibody Response and 4 the Highest Antibody Response | NY-ESO-1-specific antibodies were measured by an enzyme-linked immunosorbent assay ( ELISA) method at baseline and on days 71, 197, 365 and end of study. The results are reported as antibodies to NY-ESO-1-specific Total IgG (reciprocal titer) and were scored on a scale of 0-4 with 0 being no or minimal antibody response (reciprocal titer of 0-100) and 4 a strong antibody response (reciprocal titer of >100,000). The number of patients with each antibody response level are tabulated at each timepoint. | Day 365 | 
| NY-ESO-1 Antibody Response at End of Study Reported on a Scale of 0 to 4 With 0 Being no or Minimal Antibody Response and 4 the Highest Antibody Response | NY-ESO-1-specific antibodies were measured by an enzyme-linked immunosorbent assay ( ELISA) method at baseline and on days 71, 197, 365 and end of study. The results are reported as antibodies to NY-ESO-1-specific Total IgG (reciprocal titer) and were scored on a scale of 0-4 with 0 being no or minimal antibody response (reciprocal titer of 0-100) and 4 a strong antibody response (reciprocal titer of >100,000). The number of patients with each antibody response level are tabulated at each timepoint. | End of Study (month 18) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Phase II, Randomized Controlled Trial, Double-Blind, Cancer Vaccine, NY-ESO-1 protein, human, ISCOMATRIX®, immunological adjuvant