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

Melanoma Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00199901
• Other study ID #: LUD2003-009
• Status: Completed
• Phase: Phase 2
• Start date: September 2005
• Est. completion date: December 2011

Study information

• Verified date: October 2022
• Source: Ludwig Institute for Cancer Research
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 111
• Est. completion date: December 2011
• Est. primary completion date: December 2008
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Melanoma

Intervention

Biological:
• NY-ESO-1 ISCOMATRIX®
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).
• ISCOMATRIX® adjuvant
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).

Locations

Country	Name	City	State
Australia	Sydney Melanoma Unit - Royal Prince Alfred Hospital	Camperdown	New South Wales
Australia	Peter MacCallum Cancer Centre	East Melbourne	Victoria
Australia	Austin Health (Ludwig Institute Oncology Unit)	Heidelberg	Victoria
Australia	Sir Charles Gairdner Hospital	Nedlands	Western Australia
Australia	Newcastle Melanoma Unit - Newcastle Mater Misericordiae Hospital	Newcastle	New South Wales
Australia	Mater Medical Centre, Princess Alexandra Hospital	Woolloongabba	Queensland
New Zealand	University of Auckland (Waitemata DHB)	Auckland
United Kingdom	University Hospital - Birmingham	Birmingham
United Kingdom	Addenbrooke's Hospital	Cambridge
United Kingdom	Western Infirmary	Glasgow
United Kingdom	Royal Marsden Hospital	London
United Kingdom	St Georges Hospital	London
United Kingdom	Mount Vernon Hospital	Northwood
United Kingdom	Weston Park Hospital	Sheffield
United Kingdom	Southampton University Hospitals	Southampton

Sponsors (2)

Lead Sponsor	Collaborator
Ludwig Institute for Cancer Research	Institute of Cancer Research, United Kingdom

Countries where clinical trial is conducted

Australia,  New Zealand,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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)