AzTrials
AzTrials

MelanomaPhase 2NCT00518206

Study of NY-ESO-1 ISCOMATRIX® in Patients With Measurable Stage III or IV Melanoma

A Phase 2 study testing NY-ESO-1 ISCOMATRIX® vaccine and Cyclophosphamide in people with Melanoma, run by Ludwig Institute for Cancer Research at 2 sites in Australia.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Melanoma
What is being tested?
NY-ESO-1 ISCOMATRIX® vaccine and Cyclophosphamide
Could I receive a placebo?
No, everyone receives an active treatment
How many people
46 participants
Where
2 sitesAustralia
Study dates
28 Nov 2003to 22 Jan 2010
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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%.
Show all 14Show fewer
  • 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.

Who cannot join

  • 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.
Show all 12Show fewer
  • 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.

Trial locations and contacts

2 sites in 1 country.

Australia2 sites

  • Peter MacCallum Cancer Institute

    East Melbourne, Victoria, 3002

  • Austin Health (Ludwig Institute Oncology Unit)

    Heidelberg, Victoria, 3084

Other trials in Australia

About this study

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

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.

Read the 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.

Conditions
Melanoma
Being tested
NY-ESO-1 ISCOMATRIX® vaccine, Cyclophosphamide
Keywords
Clinical Trial, Phase 2, Cancer Vaccine, NY-ESO-1 protein, human, ISCOMATRIX, immunological adjuvant, Cyclophosphamide, T-Cells, Regulatory
Medical subject headings
Melanoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • NY-ESO-1 ISCOMATRIX® vaccineBiological

    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.

  • CyclophosphamideDrug

    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.

Study groups in NCT00518206
Study groupRoleWhat they receive
Cohort 1ExperimentalNY-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.
Receives: Biological: NY-ESO-1 ISCOMATRIX® vaccine
Cohort 2ExperimentalCyclophosphamide (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.
Receives: Biological: NY-ESO-1 ISCOMATRIX® vaccine; Drug: Cyclophosphamide

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Up to 22 months

Secondary outcomes (4)

  1. 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.

    Measured: Up to 22 months

  2. 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.

    Measured: Up to 22 months

  3. 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.

    Measured: Up to 22 months

  4. 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.

    Measured: Up to 22 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted20 Aug 2007 (estimated)
  2. Study start28 Nov 2003
  3. Primary completion22 Jan 2010
  4. Study completion22 Jan 2010

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
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)
Enrolment
46 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00518206
Sponsor's protocol ID
LUD2002-013
Other IDs
CTN Trial No.: 2007/123, CTN-Protocol# LUD2002-013AMEND
Status last verified
Oct 2022
First submitted
16 Aug 2007
Last updated
25 Oct 2022
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes: Data have been published

Publications

  • 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.

    PubMed 19276262

  • 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.

    PubMed 25662405

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing NY-ESO-1 ISCOMATRIX® vaccine and Cyclophosphamide in people with Melanoma, run by Ludwig Institute for Cancer Research at 2 sites in Australia.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 14 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 25 Oct 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in Australia. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 23 Jun 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Subjects With Best Overall Tumor Response (time frame: Up to 22 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00518206, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Oct 2022.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in