This site became the new ClinicalTrials.gov on June 19th. Learn more.
Show more
ClinicalTrials.gov Menu IMPORTANT: Listing of a study on this site does not reflect endorsement by the National Institutes of Health. Talk with a trusted healthcare professional before volunteering for a study. Read more...
ClinicalTrials.gov Menu IMPORTANT: Talk with a trusted healthcare professional before volunteering for a study. Read more...
ClinicalTrials.gov Menu
Give us feedback

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

This study has been completed.
Sponsor:
Collaborators:
Austin Health
Peter MacCallum Cancer Institute
Information provided by (Responsible Party):
Ludwig Institute for Cancer Research
ClinicalTrials.gov Identifier:
NCT00518206
First received: August 16, 2007
Last updated: April 6, 2017
Last verified: April 2017
  Purpose
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.

Condition Intervention Phase
Melanoma Biological: NY-ESO-1 ISCOMATRIX® vaccine Drug: Cyclophosphamide Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: No masking
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Ludwig Institute for Cancer Research:

Primary Outcome Measures:
  • Number of Subjects With Best Overall Tumor Response [ Time Frame: Up to 22 months ]
    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 [ Time Frame: Up to 22 months ]
    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 [ Time Frame: Up to 22 months ]
    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 they are considered to be representative of the comprehensive DTH results.

  • Humoral Immunogenicity of the NY-ESO-1 ISCOM Vaccine [ Time Frame: Up to 22 months ]
    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 [ Time Frame: Up to 22 months ]
    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.


Enrollment: 46
Actual Study Start Date: November 28, 2003
Study Completion Date: January 22, 2010
Primary Completion Date: January 22, 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Biological: 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.
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.
Biological: 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.
Drug: 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.

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.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00518206

Locations
Australia, Victoria
Peter MacCallum Cancer Institute
East Melbourne, Victoria, Australia, 3002
Austin Health (Ludwig Institute Oncology Unit)
Heidelberg, Victoria, Australia, 3084
Sponsors and Collaborators
Ludwig Institute for Cancer Research
Austin Health
Peter MacCallum Cancer Institute
Investigators
Principal Investigator: Jonathan S Cebon, FRACP, MBBS, PhD Ludwig Institute for Cancer Research - Oncology Unit
Principal Investigator: Ian D Davis, FRACP, FAChPM, MBBS, PhD Ludwig Institute for Cancer Research - Oncology Unit
  More Information

Additional Information:
Publications:
Responsible Party: Ludwig Institute for Cancer Research
ClinicalTrials.gov Identifier: NCT00518206     History of Changes
Other Study ID Numbers: LUD2002-013
CTN Trial No.: 2007/123
CTN-Protocol# LUD2002-013AMEND
Study First Received: August 16, 2007
Results First Received: April 6, 2017
Last Updated: April 6, 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Data have been published

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Ludwig Institute for Cancer Research:
Clinical Trial
Phase 2
Cancer Vaccine
NY-ESO-1 protein, human
ISCOMATRIX, immunological adjuvant
Cyclophosphamide
T-Cells, Regulatory

Additional relevant MeSH terms:
Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas
Vaccines
Cyclophosphamide
ISCOMs
Immunologic Factors
Physiological Effects of Drugs
Immunosuppressive Agents
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Adjuvants, Immunologic

ClinicalTrials.gov processed this record on July 21, 2017