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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT00518206




Registration number
NCT00518206
Ethics application status
Date submitted
16/08/2007
Date registered
20/08/2007
Date last updated
14/08/2017

Titles & IDs
Public title
Study of NY-ESO-1 ISCOMATRIX® in Patients With Measurable Stage III or IV Melanoma
Scientific 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
Secondary ID [1] 0 0
CTN Trial No.: 2007/123
Secondary ID [2] 0 0
LUD2002-013
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Melanoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Malignant melanoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Other interventions - NY-ESO-1 ISCOMATRIX® vaccine
Treatment: Drugs - Cyclophosphamide

Experimental: Cohort 1 - 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.

Experimental: Cohort 2 - 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.


Other interventions: NY-ESO-1 ISCOMATRIX® vaccine
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.

Treatment: Drugs: Cyclophosphamide
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 code [1] 0 0
Other interventions
Intervention code [2] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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.
Timepoint [1] 0 0
Up to 22 months
Secondary outcome [1] 0 0
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.
Timepoint [1] 0 0
Up to 22 months
Secondary outcome [2] 0 0
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.
Timepoint [2] 0 0
Up to 22 months
Secondary outcome [3] 0 0
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.
Timepoint [3] 0 0
Up to 22 months
Secondary outcome [4] 0 0
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.
Timepoint [4] 0 0
Up to 22 months

Eligibility
Key inclusion criteria
1. Stage IV (metastatic) or unresectable stage III malignant melanoma.

2. Measurable disease using RECIST.

3. No other effective therapy available or appropriate.

4. Expression of NY-ESO-1 or LAGE-1 by immunohistochemistry (IHC) or reverse
transcription-polymerase chain reaction (RT-PCR).

5. Expected survival of at least 4 months.

6. Karnofsky performance status of = 70%.

7. 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

8. Age = 18 years.

9. Able and willing to give written informed consent.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. 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.

2. Other malignancy within last 3 years, except for treated melanoma or non-melanoma skin
cancer or cervical cancer in situ.

3. Known immunodeficiency.

4. Known human immunodeficiency virus positivity.

5. 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.

6. Chemotherapy and/or radiotherapy within 4 weeks prior to study week 1.

7. Other immunotherapy within 4 weeks prior to study week 1.

8. Mental impairment that may have compromised the ability to give informed consent and
comply with the requirements of the study.

9. Lack of availability for immunological and clinical follow-up assessment.

10. Participation in any other clinical trial involving another investigational agent
within 4 weeks prior to enrollment.

11. Pregnancy or breastfeeding.

12. Women of childbearing potential: refusal or inability to use effective means of
contraception.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Peter MacCallum Cancer Institute - East Melbourne
Recruitment hospital [2] 0 0
Austin Health (Ludwig Institute Oncology Unit) - Heidelberg
Recruitment postcode(s) [1] 0 0
3002 - East Melbourne
Recruitment postcode(s) [2] 0 0
3084 - Heidelberg

Funding & Sponsors
Primary sponsor type
Other
Name
Ludwig Institute for Cancer Research
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
Austin Health
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Other
Name [2] 0 0
Peter MacCallum Cancer Institute
Address [2] 0 0
Country [2] 0 0

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/show/NCT00518206
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Jonathan S Cebon, FRACP, MBBS, PhD
Address 0 0
Ludwig Institute for Cancer Research - Oncology Unit
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications