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

Purpose

The purpose of this clinical trial cohort tests the effect of adding low dose cyclophosphamide to treatment with NY-ESO-1 ISCOM® vaccine, in patients with measurable advanced malignant melanoma (unresectable stage III or metastatic melanoma).

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

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label 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:

MedlinePlus related topics: Cancer Melanoma

Drug Information available for: Cyclophosphamide

U.S. FDA Resources

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

Primary Outcome Measures:

Effect of adding cyclophosphamide in the additional cohort on "Tumor Response": Measured as objective tumor response (RECIST criteria). Measured at 11 weeks but a superior response observed at a later timepoint will be recorded as the best response. [ Time Frame: 11 weeks or more ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Effect of adding cyclophosphamide in the additional cohort on "Immunological Response": Measured by DTH skin reactions, antibodies and T cell responses against NY-ESO-1. [ Time Frame: 11 weeks or more ] [ Designated as safety issue: No ]
Effect of adding cyclophosphamide in the additional cohort on "Safety": Measured as toxicity [ Time Frame: 11 weeks or more ] [ Designated as safety issue: Yes ]

Enrollment:	46
Study Start Date:	December 2003
Study Completion Date:	November 2012
Primary Completion Date:	January 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Initial Cohort NY-ESO-1 ISCOMATRIX® vaccine intramuscular injection every 4 weeks for 3 doses (1 cycle). NY-ESO-1 ISCOMATRIX® vaccine (100 microgram of NY-ESO-1 protein formulated with 120 microgram of ISCOMATRIX® adjuvant). Treatment may continue for further cycles unless other systemic melanoma treatment is required. (This cohort was completed in 2005)	Biological: NY-ESO-1 ISCOMATRIX® vaccine NY-ESO-1 ISCOMATRIX® vaccine intramuscular injection every 4 weeks for 3 doses (1 cycle). NY-ESO-1 ISCOMATRIX® vaccine (100 microgram of NY-ESO-1 protein formulated with 120 microgram of ISCOMATRIX® adjuvant). Treatment may continue for further cycles unless other systemic melanoma treatment is required. (This cohort was completed in 2005)
Experimental: Additional Cohort Cyclophosphamide (300mg/sq.m dose) intravenous injection 1 day prior to each vaccination with NY-ESO-1 ISCOMATRIX® vaccine (100 microgram of NY-ESO-1 protein formulated with 120 microgram of ISCOMATRIX® adjuvant) which is administered by intramuscular injection every 4 weeks for 3 doses (1 cycle). Treatment may continue for further cycles unless other systemic melanoma treatment is required.	Biological: NY-ESO-1 ISCOMATRIX® vaccine NY-ESO-1 ISCOMATRIX® vaccine intramuscular injection every 4 weeks for 3 doses (1 cycle). NY-ESO-1 ISCOMATRIX® vaccine (100 microgram of NY-ESO-1 protein formulated with 120 microgram of ISCOMATRIX® adjuvant). Treatment may continue for further cycles unless other systemic melanoma treatment is required. (This cohort was completed in 2005) Drug: Cyclophosphamide Cyclophosphamide (300mg/sq.m dose) intravenous injection 1 day prior to each of 3x fourth weekly intramuscular injections with NY-ESO-1 ISCOMATRIX® vaccine (100 microgram of NY-ESO-1 protein formulated with 120 microgram of ISCOMATRIX® adjuvant). Treatment may continue for further cycles unless other systemic melanoma treatment is required.

Arms

Assigned Interventions

Experimental: Initial Cohort

NY-ESO-1 ISCOMATRIX® vaccine intramuscular injection every 4 weeks for 3 doses (1 cycle). NY-ESO-1 ISCOMATRIX® vaccine (100 microgram of NY-ESO-1 protein formulated with 120 microgram of ISCOMATRIX® adjuvant). Treatment may continue for further cycles unless other systemic melanoma treatment is required. (This cohort was completed in 2005)

Biological: NY-ESO-1 ISCOMATRIX® vaccine

NY-ESO-1 ISCOMATRIX® vaccine intramuscular injection every 4 weeks for 3 doses (1 cycle). NY-ESO-1 ISCOMATRIX® vaccine (100 microgram of NY-ESO-1 protein formulated with 120 microgram of ISCOMATRIX® adjuvant). Treatment may continue for further cycles unless other systemic melanoma treatment is required. (This cohort was completed in 2005)

Experimental: Additional Cohort

Cyclophosphamide (300mg/sq.m dose) intravenous injection 1 day prior to each vaccination with NY-ESO-1 ISCOMATRIX® vaccine (100 microgram of NY-ESO-1 protein formulated with 120 microgram of ISCOMATRIX® adjuvant) which is administered by intramuscular injection every 4 weeks for 3 doses (1 cycle). Treatment may continue for further cycles unless other systemic melanoma treatment is required.

Biological: NY-ESO-1 ISCOMATRIX® vaccine

NY-ESO-1 ISCOMATRIX® vaccine intramuscular injection every 4 weeks for 3 doses (1 cycle). NY-ESO-1 ISCOMATRIX® vaccine (100 microgram of NY-ESO-1 protein formulated with 120 microgram of ISCOMATRIX® adjuvant). Treatment may continue for further cycles unless other systemic melanoma treatment is required. (This cohort was completed in 2005)

Drug: Cyclophosphamide

Cyclophosphamide (300mg/sq.m dose) intravenous injection 1 day prior to each of 3x fourth weekly intramuscular injections with NY-ESO-1 ISCOMATRIX® vaccine (100 microgram of NY-ESO-1 protein formulated with 120 microgram of ISCOMATRIX® adjuvant). Treatment may continue for further cycles unless other systemic melanoma treatment is required.

Detailed Description:

This clinical trial cohort tests the combination of NY-ESO-1 ISCOMATRIX® vaccine given after low dose cyclophosphamide in patients with advanced melanoma.

NY-ESO-1 protein is an immune target found in many cancers including melanoma. ISCOMATRIX® adjuvant enhances immune responses. Low dose cyclophosphamide has been shown to suppress a population of lymphocytes called "regulatory T cells". Regulatory T cells can interfere with immune responses in patients with cancer. The rationale for treating this new cohort of patients in the study is to use a small dose of cyclophosphamide to suppress the regulatory T cells and thus try to increase patient responses to the NY-ESO-1 ISCOMATRIX® vaccine.

Eligible patients will receive three intramuscular injections of NY-ESO-1 ISCOM® vaccine at approximately four-week intervals (week 1, week 5, week 9). Low dose cyclophosphamide will be administered by intravenous infusion one day prior to the each NY-ESO-1 ISCOM® vaccine.

Tumor evaluations (CT scans and physical evaluations), safety evaluation (blood tests and medical reviews) and immunological testing (special DTH skin tests and blood immunology tests) will be performed before, during and at the end of the 11 week treatment cycle. Treatment may continue for further cycles unless there is a reason to remove the patient from study.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Stage IV (metastatic) or unresectable stage III malignant melanoma.
Tumor expression of NY-ESO-1 antigen by immunohistochemistry.
Measurable disease (RECIST criteria).
No other effective therapy available or appropriate.
Expected survival of at least 4 months.
Performance status (Karnofsky) 70% or greater.
Vital laboratory parameters within normal range, or protocol specified ranges.
Age 18 years or older.
Able to give written informed consent.

Exclusion Criteria:

Other serious or significant illnesses.
Other malignancy within last 3 years, except for treated melanoma or non-melanoma skin cancer and cervical cancer in situ.
Known immunodeficiency
Known HIV positivity
Using systemic immunosuppressive drugs. (Exceptions: Specific COX-2 inhibitors; low dose aspirin for acute cardiovascular event prevention; topical/inhaled steroids)
Chemotherapy, immunotherapy or radiotherapy within last four weeks.
Participation in prior clinical trial involving an investigational agent within last 4 weeks.
Not available for immunological and clinical follow-up assessments.
Pregnancy or breastfeeding.
Refusal or inability to use effective means of contraception for women of childbearing potential.
Mental impairment that may compromise ability to give informed consent and to comply with study requirements.

Contacts and Locations

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

Locations

Australia, Victoria
Peter MacCallum Cancer Centre
East Melbourne, Victoria, Australia, 3002
Austin Health (Ludwig Institute Oncology Unit)
Heidelberg (Melbourne), Victoria, Australia, 3084

Sponsors and Collaborators

Ludwig Institute for Cancer Research

Investigators

Principal Investigator:	Prof. Jonathan S Cebon, FRACP, MBBS, PhD	Ludwig Institute for Cancer Research
Principal Investigator:	A/Prof Ian D Davis, FRACP, FAChPM, MBBS, PhD	Ludwig Institute for Cancer Research

More Information

No publications provided

Responsible Party:	N/A (non-FDA (non-IND) study)
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
Last Updated:	February 27, 2013
Health Authority:	Australia: Department of Health and Ageing Therapeutic Goods Administration

Keywords provided by Ludwig Institute for Cancer Research:

Clinical Trial
Phase II
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
Adjuvants, Immunologic
Cyclophosphamide
Immunologic Factors

Physiological Effects of Drugs
Pharmacologic Actions
Immunosuppressive Agents
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists

ClinicalTrials.gov processed this record on May 16, 2013