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

NCT00518206 | Completed Phase 2 Results

• 3 other identifiers: LUD2002-013CTN Trial No.: 2007/123CTN-Protocol# LUD2002-013AMEND
• Study Type: interventional
• Target: 46
• Locations: 1 country
• Sites: 2

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.

Conditions

Melanoma

Keywords

Clinical Trial; Phase 2; Cancer Vaccine; NY-ESO-1 protein, human; ISCOMATRIX, immunological adjuvant; Cyclophosphamide; T-Cells, Regulatory

Outcome Measures

Primary Outcomes (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.

  Up to 22 months

Secondary Outcomes (4)

• Cellular Immunogenicity of the NY-ESO-1 ISCOM Vaccine

  Up to 22 months

• Post-Vaccination Delayed-type Hypersensitivity (DTH) Reactions

  Up to 22 months

• Humoral Immunogenicity of the NY-ESO-1 ISCOM Vaccine

  Up to 22 months

• Number of Subjects With Treatment-emergent Adverse Events

  Up to 22 months

Study Arms (2)

Cohort 1

EXPERIMENTAL

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

Cohort 2

EXPERIMENTAL

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; Drug: Cyclophosphamide

Interventions

NY-ESO-1 ISCOMATRIX® vaccine BIOLOGICAL

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.

Cohort 1; Cohort 2

Cyclophosphamide DRUG

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.

Cohort 2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Ludwig Institute for Cancer Research: lead
• Austin Health: collaborator
• Peter MacCallum Cancer Institute: collaborator

Study Sites (2)

Peter MacCallum Cancer Institute

East Melbourne, Victoria, 3002, Australia

Location

Austin Health (Ludwig Institute Oncology Unit)

Heidelberg, Victoria, 3084, Australia

Location

Related Publications (2)

• 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.

  PMID: 19276262 RESULT

• 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.

  PMID: 25662405 RESULT

MeSH Terms

Conditions

Melanoma

Interventions

Cyclophosphamide

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Results Point of Contact

• Title: Jonathan Skipper PhD
• Organization: Ludwig Institute for Cancer Research

jskipper@lcr.org

12124501539

Study Officials

• 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

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: August 16, 2007
• First Posted: August 20, 2007
• Study Start: November 28, 2003
• Primary Completion: January 22, 2010
• Study Completion: January 22, 2010
• Last Updated: October 25, 2022
• Results First Posted: June 23, 2017

Record last verified: 2022-10

Data Sharing

• IPD Sharing: Will share

Locations

AU (2)