Back to resultsStudy of NY-ESO-1 ISCOMATRIX® in Patients With Measurable Stage III or IV Melanoma
Primary Purpose
Melanoma
Status
Completed
Phase
Phase 2
Locations
Australia
Study Type
Interventional
Intervention
NY-ESO-1 ISCOMATRIX® vaccine
Cyclophosphamide
Sponsored by
About this trial
This is an interventional treatment trial for Melanoma focused on measuring Clinical Trial, Phase 2, Cancer Vaccine, NY-ESO-1 protein, human, ISCOMATRIX, immunological adjuvant, Cyclophosphamide, T-Cells, Regulatory
Eligibility Criteria
Inclusion Criteria:
- Stage IV (metastatic) or unresectable stage III malignant melanoma.
- Measurable disease using RECIST.
- No other effective therapy available or appropriate.
- Expression of NY-ESO-1 or LAGE-1 by immunohistochemistry (IHC) or reverse transcription-polymerase chain reaction (RT-PCR).
- Expected survival of at least 4 months.
- Karnofsky performance status of ≥ 70%.
Within 3 weeks prior to first administration of study drug, the following laboratory parameters were required to be within the ranges specified:
- Hemoglobin ≥ 100 g/L
- Platelets ≥ 100 x 10^9/L
- International normalized ratio ≤ 2.0
- Creatinine ≤ 0.2 mmol/L
- Bilirubin ≤ 30 mmol/L
- Age ≥ 18 years.
- Able and willing to give written informed consent.
Exclusion Criteria:
- Other serious illnesses, eg, serious infections requiring antibiotics, bleeding disorders, or any condition that in the opinion of the Investigator would have interfered with the ability of the patient to complete all study requirements.
- Other malignancy within last 3 years, except for treated melanoma or non-melanoma skin cancer or cervical cancer in situ.
- Known immunodeficiency.
- Known human immunodeficiency virus positivity.
- Concomitant systemic treatment with corticosteroids, anti-histaminic drugs, or nonsteroidal anti-inflammatory drugs. Specific cyclooxygenase-2 (COX-2) inhibitors, low-dose aspirin for the prevention of an acute cardiovascular event, and topical or inhaled steroids were permitted.
- Chemotherapy and/or radiotherapy within 4 weeks prior to study week 1.
- Other immunotherapy within 4 weeks prior to study week 1.
- Mental impairment that may have compromised the ability to give informed consent and comply with the requirements of the study.
- Lack of availability for immunological and clinical follow-up assessment.
- Participation in any other clinical trial involving another investigational agent within 4 weeks prior to enrollment.
- Pregnancy or breastfeeding.
- Women of childbearing potential: refusal or inability to use effective means of contraception.
Sites / Locations
- Peter MacCallum Cancer Institute
- Austin Health (Ludwig Institute Oncology Unit)
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Cohort 1
Cohort 2
Arm Description
NY-ESO-1 ISCOM vaccine (100 μg of the NY-ESO-1 protein formulated with 120 μg of ISCOM adjuvant) administered as an intramuscular injection every 4 weeks for 3 doses in every cycle.
Cyclophosphamide (300 mg/m^2) administered as an intravenous injection 1 day prior to each vaccination with NY-ESO-1 ISCOM (100 μg of the NY-ESO-1 protein formulated with 120 μg of ISCOM adjuvant), which was administered as an intramuscular injection every 4 weeks for 3 doses in every cycle.
Outcomes
Primary Outcome Measures
Number of Subjects With Best Overall Tumor Response
Tumor responses were evaluated using computed tomography and categorized according to RECIST (version 1.0) at baseline, at week 11, between weeks 23 and 25, and every 12 weeks thereafter. Per RECIST, target lesions are categorized as follows: Complete Response (CR): Disappearance of all target lesions [no evidence of disease]; Partial Response (PR): ≥ 30% decrease in the sum of the longest diameter of target lesions; Progressive Disease (PD): ≥ 20% increase in the sum of the longest diameter of target lesions; Stable Disease (SD): small changes that do not meet above criteria.
Secondary Outcome Measures
Cellular Immunogenicity of the NY-ESO-1 ISCOM Vaccine
Blood samples were drawn to measure cellular response at pretreatment and weeks 3, 7, 11, between weeks 23 and 25, week 33, and every 12 weeks thereafter. Cellular immunity included an assay for gamma interferon-producing T cells and enumeration of NY-ESO-1b-specific T cells, detected by fluorescent labeled human leukocyte antigen (HLA)-A2 tetramers carrying the NY-ESO-1b peptide, expressed as percent positive staining of CD4+ and CD8+ T cells. Data are presented for CD4+ and CD8+ T-cell responses (not mutually exclusive) that were pre-existing at baseline (BL) or presented at any time post-BL.
Post-Vaccination Delayed-type Hypersensitivity (DTH) Reactions
NY-ESO-1-specific DTH was measured by intradermal injection with the full-length NY-ESO-1 protein, NY-ESO-1b peptide, and NY-ESO-1 DP4 peptide at pretreatment, week 11, and between week 23 and 25. DTH reactions (eg, local skin irritation) were evaluated 2 days after DTH injections. Data presented are based on injections with the full-length peptide, as these data are considered to be representative of the comprehensive DTH results.
Humoral Immunogenicity of the NY-ESO-1 ISCOM Vaccine
Blood samples were drawn to measure humoral immunologic response at pretreatment and weeks 3, 7, 11, 33, and every 12 weeks thereafter. Humoral immunity was assessed by measurement of antibodies to NY-ESO-1 by enzyme-linked immunosorbent assay (ELISA). Data are presented according to baseline (BL) NY-ESO-1 antibody positivity and the time to seroconversion, if applicable.
Number of Subjects With Treatment-emergent Adverse Events
Toxicity was graded in accordance with the National Cancer Institute Common Terminology Criteria for Adverse Events (version 3.0). Treatment-emergent adverse events (TEAEs) were reported based on clinical laboratory tests, physical examinations, and vital signs from pre-treatment through the study period. Dose-limiting toxicity was defined as any treatment-related grade 4 toxicity or any grade 3 toxicity, excluding grade 3 skin necrosis at the site of the delayed-type hypersensitivity reaction, fever, or asymptomatic hyperglycemia that improved to baseline within 3 weeks of onset.
Full Information
NCT ID
NCT00518206
First Posted
August 16, 2007
Last Updated
October 3, 2022
Sponsor
Ludwig Institute for Cancer Research
Collaborators
Austin Health, Peter MacCallum Cancer Institute
1. Study Identification
Unique Protocol Identification Number
NCT00518206
Brief Title
Study of NY-ESO-1 ISCOMATRIX® in Patients With Measurable Stage III or IV Melanoma
Official Title
A Phase II Study of the Clinical and Immunological Effects of NY-ESO-1 ISCOM® Vaccine in Patients With Measurable Stage III and IV Malignant Melanoma
Study Type
Interventional
2. Study Status
Record Verification Date
October 2022
Overall Recruitment Status
Completed
Study Start Date
November 28, 2003 (Actual)
Primary Completion Date
January 22, 2010 (Actual)
Study Completion Date
January 22, 2010 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Ludwig Institute for Cancer Research
Collaborators
Austin Health, Peter MacCallum Cancer Institute
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
This was a Phase 2, open-label study of the NY-ESO-1 ISCOMATRIX® (ISCOM) vaccine administered as an intramuscular injection given every 4 weeks to subjects with measurable advanced malignant melanoma. Study objectives included determination of the anticancer activity, cellular and humoral immunogenicity, and safety and tolerability of the NY-ESO-1 ISCOM vaccine administered alone or preceded by a single administration of low-dose cyclophosphamide.
Detailed Description
In Cohort 1, 6 subjects were initially vaccinated with the NY-ESO-1 ISCOM vaccine at a dose of 100 µg of the NY-ESO-1 protein + 120 µg of the ISCOM adjuvant. These 6 subjects were monitored for dose-limiting toxicity (DLT) for 7 days after the first vaccination. Upon observation of tolerability (ie, < 2/6 subjects with DLT), enrollment proceeded to a total accrual of approximately 25 subjects. Subjects received 3 vaccinations administered every 4 weeks (ie, weeks 1, 5, and 9) followed by immunological and clinical response evaluations, with clinical responses categorized according to the Response Evaluation Criteria in Solid Tumors (RECIST). In the absence of disease progression, subjects may have received 3 additional vaccinations administered every 4 weeks, followed by additional vaccinations administered every 12 weeks thereafter until development of disease progression or other criteria for discontinuation.
In Cohort 2, subjects received the NY-ESO-1 ISCOM vaccine on the same schedule as described for Cohort 1, but Cohort 2 subjects also received a single intravenous infusion of low-dose cyclophosphamide 1 day prior to each NY-ESO-1 ISCOM vaccination. If responses were observed in 2 of 16 subjects initially treated in Cohort 2, then 9 additional subjects were to be accrued to Cohort 2, for a total potential accrual of 25 subjects.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Melanoma
Keywords
Clinical Trial, Phase 2, Cancer Vaccine, NY-ESO-1 protein, human, ISCOMATRIX, immunological adjuvant, Cyclophosphamide, T-Cells, Regulatory
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
Cohort 1 was enrolled first, in which subjects received the NY-ESO-1 ISCOM vaccine. Enrollment then proceeded to Cohort 2, in which subjects received the NY-ESO-1 ISCOM vaccine and low-dose cyclophosphamide.
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
46 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Cohort 1
Arm Type
Experimental
Arm Description
NY-ESO-1 ISCOM vaccine (100 μg of the NY-ESO-1 protein formulated with 120 μg of ISCOM adjuvant) administered as an intramuscular injection every 4 weeks for 3 doses in every cycle.
Arm Title
Cohort 2
Arm Type
Experimental
Arm Description
Cyclophosphamide (300 mg/m^2) administered as an intravenous injection 1 day prior to each vaccination with NY-ESO-1 ISCOM (100 μg of the NY-ESO-1 protein formulated with 120 μg of ISCOM adjuvant), which was administered as an intramuscular injection every 4 weeks for 3 doses in every cycle.
Intervention Type
Biological
Intervention Name(s)
NY-ESO-1 ISCOMATRIX® vaccine
Intervention Description
NY-ESO-1 ISCOM vaccine (100 μg of the NY-ESO-1 protein formulated with 120 μg of ISCOM adjuvant) administered as an intramuscular injection every 4 weeks for 3 doses in every cycle.
Intervention Type
Drug
Intervention Name(s)
Cyclophosphamide
Intervention Description
Cyclophosphamide (300 mg/m^2) administered as an intravenous injection 1 day prior to each vaccination with NY-ESO-1 ISCOM (100 μg of the NY-ESO-1 protein formulated with 120 μg of ISCOM adjuvant), which was administered as an intramuscular injection every 4 weeks for 3 doses in every cycle.
Primary Outcome Measure Information:
Title
Number of Subjects With Best Overall Tumor Response
Description
Tumor responses were evaluated using computed tomography and categorized according to RECIST (version 1.0) at baseline, at week 11, between weeks 23 and 25, and every 12 weeks thereafter. Per RECIST, target lesions are categorized as follows: Complete Response (CR): Disappearance of all target lesions [no evidence of disease]; Partial Response (PR): ≥ 30% decrease in the sum of the longest diameter of target lesions; Progressive Disease (PD): ≥ 20% increase in the sum of the longest diameter of target lesions; Stable Disease (SD): small changes that do not meet above criteria.
Time Frame
Up to 22 months
Secondary Outcome Measure Information:
Title
Cellular Immunogenicity of the NY-ESO-1 ISCOM Vaccine
Description
Blood samples were drawn to measure cellular response at pretreatment and weeks 3, 7, 11, between weeks 23 and 25, week 33, and every 12 weeks thereafter. Cellular immunity included an assay for gamma interferon-producing T cells and enumeration of NY-ESO-1b-specific T cells, detected by fluorescent labeled human leukocyte antigen (HLA)-A2 tetramers carrying the NY-ESO-1b peptide, expressed as percent positive staining of CD4+ and CD8+ T cells. Data are presented for CD4+ and CD8+ T-cell responses (not mutually exclusive) that were pre-existing at baseline (BL) or presented at any time post-BL.
Time Frame
Up to 22 months
Title
Post-Vaccination Delayed-type Hypersensitivity (DTH) Reactions
Description
NY-ESO-1-specific DTH was measured by intradermal injection with the full-length NY-ESO-1 protein, NY-ESO-1b peptide, and NY-ESO-1 DP4 peptide at pretreatment, week 11, and between week 23 and 25. DTH reactions (eg, local skin irritation) were evaluated 2 days after DTH injections. Data presented are based on injections with the full-length peptide, as these data are considered to be representative of the comprehensive DTH results.
Time Frame
Up to 22 months
Title
Humoral Immunogenicity of the NY-ESO-1 ISCOM Vaccine
Description
Blood samples were drawn to measure humoral immunologic response at pretreatment and weeks 3, 7, 11, 33, and every 12 weeks thereafter. Humoral immunity was assessed by measurement of antibodies to NY-ESO-1 by enzyme-linked immunosorbent assay (ELISA). Data are presented according to baseline (BL) NY-ESO-1 antibody positivity and the time to seroconversion, if applicable.
Time Frame
Up to 22 months
Title
Number of Subjects With Treatment-emergent Adverse Events
Description
Toxicity was graded in accordance with the National Cancer Institute Common Terminology Criteria for Adverse Events (version 3.0). Treatment-emergent adverse events (TEAEs) were reported based on clinical laboratory tests, physical examinations, and vital signs from pre-treatment through the study period. Dose-limiting toxicity was defined as any treatment-related grade 4 toxicity or any grade 3 toxicity, excluding grade 3 skin necrosis at the site of the delayed-type hypersensitivity reaction, fever, or asymptomatic hyperglycemia that improved to baseline within 3 weeks of onset.
Time Frame
Up to 22 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Stage IV (metastatic) or unresectable stage III malignant melanoma.
Measurable disease using RECIST.
No other effective therapy available or appropriate.
Expression of NY-ESO-1 or LAGE-1 by immunohistochemistry (IHC) or reverse transcription-polymerase chain reaction (RT-PCR).
Expected survival of at least 4 months.
Karnofsky performance status of ≥ 70%.
Within 3 weeks prior to first administration of study drug, the following laboratory parameters were required to be within the ranges specified:
Hemoglobin ≥ 100 g/L
Platelets ≥ 100 x 10^9/L
International normalized ratio ≤ 2.0
Creatinine ≤ 0.2 mmol/L
Bilirubin ≤ 30 mmol/L
Age ≥ 18 years.
Able and willing to give written informed consent.
Exclusion Criteria:
Other serious illnesses, eg, serious infections requiring antibiotics, bleeding disorders, or any condition that in the opinion of the Investigator would have interfered with the ability of the patient to complete all study requirements.
Other malignancy within last 3 years, except for treated melanoma or non-melanoma skin cancer or cervical cancer in situ.
Known immunodeficiency.
Known human immunodeficiency virus positivity.
Concomitant systemic treatment with corticosteroids, anti-histaminic drugs, or nonsteroidal anti-inflammatory drugs. Specific cyclooxygenase-2 (COX-2) inhibitors, low-dose aspirin for the prevention of an acute cardiovascular event, and topical or inhaled steroids were permitted.
Chemotherapy and/or radiotherapy within 4 weeks prior to study week 1.
Other immunotherapy within 4 weeks prior to study week 1.
Mental impairment that may have compromised the ability to give informed consent and comply with the requirements of the study.
Lack of availability for immunological and clinical follow-up assessment.
Participation in any other clinical trial involving another investigational agent within 4 weeks prior to enrollment.
Pregnancy or breastfeeding.
Women of childbearing potential: refusal or inability to use effective means of contraception.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jonathan S Cebon, FRACP, MBBS, PhD
Organizational Affiliation
Ludwig Institute for Cancer Research - Oncology Unit
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Ian D Davis, FRACP, FAChPM, MBBS, PhD
Organizational Affiliation
Ludwig Institute for Cancer Research - Oncology Unit
Official's Role
Principal Investigator
Facility Information:
Facility Name
Peter MacCallum Cancer Institute
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
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
Data have been published
Citations:
PubMed Identifier
19276262
Citation
Nicholaou T, Ebert LM, Davis ID, McArthur GA, Jackson H, Dimopoulos N, Tan B, Maraskovsky E, Miloradovic L, Hopkins W, Pan L, Venhaus R, Hoffman EW, Chen W, Cebon J. Regulatory T-cell-mediated attenuation of T-cell responses to the NY-ESO-1 ISCOMATRIX vaccine in patients with advanced malignant melanoma. Clin Cancer Res. 2009 Mar 15;15(6):2166-73. doi: 10.1158/1078-0432.CCR-08-2484. Epub 2009 Mar 10.
Results Reference
result
PubMed Identifier
25662405
Citation
Klein O, Davis ID, McArthur GA, Chen L, Haydon A, Parente P, Dimopoulos N, Jackson H, Xiao K, Maraskovsky E, Hopkins W, Stan R, Chen W, Cebon J. Low-dose cyclophosphamide enhances antigen-specific CD4(+) T cell responses to NY-ESO-1/ISCOMATRIX vaccine in patients with advanced melanoma. Cancer Immunol Immunother. 2015 Apr;64(4):507-18. doi: 10.1007/s00262-015-1656-x. Epub 2015 Feb 7.
Results Reference
result
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Study of NY-ESO-1 ISCOMATRIX® in Patients With Measurable Stage III or IV Melanoma
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