Back to resultsStudy of NY-ESO-1 ISCOMATRIX® in Patients With High-risk, Resected Melanoma
Primary Purpose
Melanoma
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
NY-ESO-1 ISCOMATRIX®
ISCOMATRIX® adjuvant
Sponsored by
About this trial
This is an interventional treatment trial for Melanoma focused on measuring Phase II, Randomized Controlled Trial, Double-Blind, Cancer Vaccine, NY-ESO-1 protein, human, ISCOMATRIX®, immunological adjuvant
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.
Sites / Locations
- Sydney Melanoma Unit - Royal Prince Alfred Hospital
- Newcastle Melanoma Unit - Newcastle Mater Misericordiae Hospital
- Mater Medical Centre, Princess Alexandra Hospital
- Peter MacCallum Cancer Centre
- Austin Health (Ludwig Institute Oncology Unit)
- Sir Charles Gairdner Hospital
- University of Auckland (Waitemata DHB)
- University Hospital - Birmingham
- Addenbrooke's Hospital
- Western Infirmary
- St Georges Hospital
- Royal Marsden Hospital
- Mount Vernon Hospital
- Weston Park Hospital
- Southampton University Hospitals
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Placebo Comparator
Arm Label
Vaccine
Adjuvant Alone
Arm Description
NY-ESO-1 ISCOMATRIX® vaccine
ISCOMATRIX® adjuvant alone
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
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.
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.
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.
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.
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.
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.
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.
Full Information
NCT ID
NCT00199901
First Posted
September 16, 2005
Last Updated
October 3, 2022
Sponsor
Ludwig Institute for Cancer Research
Collaborators
Institute of Cancer Research, United Kingdom
1. Study Identification
Unique Protocol Identification Number
NCT00199901
Brief Title
Study of NY-ESO-1 ISCOMATRIX® in Patients With High-risk, Resected Melanoma
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
Study Type
Interventional
2. Study Status
Record Verification Date
October 2022
Overall Recruitment Status
Completed
Study Start Date
September 2005 (undefined)
Primary Completion Date
December 2008 (Actual)
Study Completion Date
December 2011 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Ludwig Institute for Cancer Research
Collaborators
Institute of Cancer Research, United Kingdom
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Melanoma
Keywords
Phase II, Randomized Controlled Trial, Double-Blind, Cancer Vaccine, NY-ESO-1 protein, human, ISCOMATRIX®, immunological adjuvant
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
111 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Vaccine
Arm Type
Active Comparator
Arm Description
NY-ESO-1 ISCOMATRIX® vaccine
Arm Title
Adjuvant Alone
Arm Type
Placebo Comparator
Arm Description
ISCOMATRIX® adjuvant alone
Intervention Type
Biological
Intervention Name(s)
NY-ESO-1 ISCOMATRIX®
Intervention Description
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).
Intervention Type
Biological
Intervention Name(s)
ISCOMATRIX® adjuvant
Intervention Description
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).
Primary Outcome Measure Information:
Title
Rate of Relapse-free Survival at 18 Months
Description
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.
Time Frame
18 months
Secondary Outcome Measure Information:
Title
Number of Patients With Treatment -Emergent Adverse Events (TEAEs)
Description
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.
Time Frame
18 months
Title
Relapse-Free Survival During the Entire Period of Observation (up to 6 Years).
Description
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.
Time Frame
through study completion; up to 6 years
Title
Overall Survival
Description
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.
Time Frame
through study completion; up to 6 years
Title
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
Description
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.
Time Frame
Baseline
Title
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
Description
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.
Time Frame
Day 71
Title
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
Description
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.
Time Frame
Day 197
Title
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
Description
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.
Time Frame
Day 365
Title
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
Description
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.
Time Frame
End of Study (month 18)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Prof. Jonathan S Cebon, MBBS PhD
Organizational Affiliation
Ludwig Institute for Cancer Research
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Prof. Martin Gore, MBBS PhD
Organizational Affiliation
The Royal Marsden Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Sydney Melanoma Unit - Royal Prince Alfred Hospital
City
Camperdown
State/Province
New South Wales
ZIP/Postal Code
2050
Country
Australia
Facility Name
Newcastle Melanoma Unit - Newcastle Mater Misericordiae Hospital
City
Newcastle
State/Province
New South Wales
ZIP/Postal Code
2298
Country
Australia
Facility Name
Mater Medical Centre, Princess Alexandra Hospital
City
Woolloongabba
State/Province
Queensland
ZIP/Postal Code
4102
Country
Australia
Facility Name
Peter MacCallum Cancer Centre
City
East Melbourne
State/Province
Victoria
ZIP/Postal Code
3002
Country
Australia
Facility Name
Austin Health (Ludwig Institute Oncology Unit)
City
Heidelberg
State/Province
Victoria
ZIP/Postal Code
3084
Country
Australia
Facility Name
Sir Charles Gairdner Hospital
City
Nedlands
State/Province
Western Australia
ZIP/Postal Code
6009
Country
Australia
Facility Name
University of Auckland (Waitemata DHB)
City
Auckland
Country
New Zealand
Facility Name
University Hospital - Birmingham
City
Birmingham
ZIP/Postal Code
B29 6JD
Country
United Kingdom
Facility Name
Addenbrooke's Hospital
City
Cambridge
ZIP/Postal Code
CB2 2QQ
Country
United Kingdom
Facility Name
Western Infirmary
City
Glasgow
ZIP/Postal Code
G11 6NT
Country
United Kingdom
Facility Name
St Georges Hospital
City
London
ZIP/Postal Code
SW17 0RE
Country
United Kingdom
Facility Name
Royal Marsden Hospital
City
London
ZIP/Postal Code
SW3 6JJ
Country
United Kingdom
Facility Name
Mount Vernon Hospital
City
Northwood
ZIP/Postal Code
HA6 2RN
Country
United Kingdom
Facility Name
Weston Park Hospital
City
Sheffield
ZIP/Postal Code
S10 2SJ
Country
United Kingdom
Facility Name
Southampton University Hospitals
City
Southampton
ZIP/Postal Code
SO16 6YD
Country
United Kingdom
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Study of NY-ESO-1 ISCOMATRIX® in Patients With High-risk, Resected Melanoma
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