Immunization With 8 Peptides Mixed With CpG 7909 or Montanide ISA51 in Patients With Metastatic Cutaneous Melanoma

NCT00145158 | Terminated Phase 1 Results

• 1 other identifier: LUD2003-007
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 2

Brief Summary

The purposes of this study are to describe the immune response to individual peptides after immunization with a combination of 8 peptides and CpG 7909 or Montanide ISA51; to determine the safety of the vaccines and; to document the tumor response in patients receiving the vaccines.

Conditions

Malignant Melanoma

Keywords

Melanoma; Vaccine; Peptide; Montanide

Outcome Measures

Primary Outcomes (1)

• Number of Patients With Cytotoxic T-lymphocyte (CTL) Response to Individual Peptides After Immunization With a Combination of 8 Peptides and CpG 7909 or Montanide ISA51.

  Peripheral blood lymphocytes (PBL) were collected prior to the first dose of vaccine and after the completion of the six vaccinations in Week 13. Specific CTL directed against the 8 vaccine antigens ( NA17.A2, MAGE-1.A2, MAGE-3.A2, MAGE-4.A2, MAGE-10.A2, MAGE-C2.A2 and Tyrosinase.A2) was assessed by using re-stimulation in vitro, followed by staining with the corresponding tetramer (MLPC/tetramer). A patient was considered to have a positive CTL response when the post-vaccine CTL response against at least one of the vaccine antigens was ten times higher than the corresponding pre-treatment value.

  Week 13

Secondary Outcomes (3)

• Number of Patients With Dose Limiting Toxicities (DLT).

  up to Week 13

• Number of Patients With Tumor Responses After Immunization With a Combination of 8 Peptides and CpG 7909 or Montanide ISA51 as Measured by RECIST.

  Week 13

• Number of Patients With Cytotoxic T-lymphocyte (CTL) Responses and Tumor Expression of the Corresponding Genes.

  Week 13

Study Arms (2)

Cohort 1: 8 HLA-A2-restricted peptides and CpG 7909

EXPERIMENTAL

Patients were immunized with a combination of 8 peptides corresponding to defined tumor antigens (MAGE-1.A2, MAGE-3.A2, MAGE-4.A2, MAGE-10.A2, MAGE-C2.A2, NY-ESO-1.A2, NA17.A2 and Tyrosinase.A2), mixed with CpG 7909. Patients received six sequential injections at 2-week intervals.

Biological: 8 HLA-A2-restricted peptides and CpG 7909

Cohort 2: 8 HLA-A2-Restricted Peptides and Montanide ISA51

EXPERIMENTAL

Patients were immunized with a combination of 8 peptides corresponding to defined tumor antigens (MAGE-1.A2, MAGE-3.A2, MAGE-4.A2, MAGE-10.A2, MAGE-C2.A2, NY-ESO-1.A2, and NA17.A2), mixed with Montanide ISA 51. Tyrosinase.A2 was administered without Montanide ISA51. Patients received six sequential injections at 2-week intervals.

Biological: 8 HLA-A2-restricted peptides and Montanide ISA51

Interventions

8 HLA-A2-restricted peptides and Montanide ISA51 BIOLOGICAL

Cohort 2: 8 HLA-A2-Restricted Peptides and Montanide ISA51

8 HLA-A2-restricted peptides and CpG 7909 BIOLOGICAL

Cohort 1: 8 HLA-A2-restricted peptides and CpG 7909

Eligibility Criteria

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

You may qualify if:

• Histologically proven cutaneous melanoma, or clear cell sarcoma, which is considered as a subtype of melanoma.
• Melanoma must be at one of the following AJCC 2002 stages:
• Regional metastatic disease (any T; N2b, N2c or N3; M0).
• Distant metastatic disease (any T; any N; M1a, M1b or M1c), except brain or leptomeningeal localizations, and except elevated LDH.
• Patients must be HLA-A2.
• A pre-immune tumor biopsy must be kept frozen for post-study PCR analysis.
• Presence of at least one measurable or non-measurable tumor lesion.
• Expected survival of at least 3 months.
• Karnofsky performance scale ≥70 or WHO performance status of 0 or 1.
• Within the last 4 weeks prior to study day 1, vital laboratory parameters should be within normal range, except for the following laboratory parameters, which must be within the ranges specified:
• Lab Parameter Range
• Hemoglobin ≥ 10 g/dl or ≥ 6,25 mmol/l
• Granulocytes ≥ 1,500/µl
• Lymphocytes ≥ 700/µl
• Platelets ≥ 100,000/µl

You may not qualify if:

• Previous treatment with more than one regimen of systemic chemotherapy, combined or not with non-specific immunotherapy such as interferon alpha or interleukins. Chemoimmunotherapy or radiotherapy must be stopped within the preceding 4 weeks (6 weeks for nitrosoureas and mitomycin C).
• Clinically significant heart disease (NYHA Class III or IV) i.e. NYHA class 3 congestive heart failure; myocardial infarction within the past six months; unstable angina; coronary angioplasty within the past 6 months; uncontrolled atrial or ventricular cardiac arrhythmias.
• Other serious acute or chronic illnesses, e.g. active infections requiring antibiotics, bleeding disorders, or other conditions requiring concurrent medications not allowed during this study.
• Other malignancy within 3 years prior to entry into the study, except for treated non-melanoma skin cancer and cervical carcinoma in situ.
• Lack of availability for immunological and clinical follow-up assessments.
• 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

Study Sites (2)

Clinique Universitaires St-Luc

Brussels, B-1200, Belgium

Location

Ludwig Institute for Cancer Research

Brussels, B-1200, Belgium

Location

Related Publications (3)

• Marchand M, van Baren N, Weynants P, Brichard V, Dreno B, Tessier MH, Rankin E, Parmiani G, Arienti F, Humblet Y, Bourlond A, Vanwijck R, Lienard D, Beauduin M, Dietrich PY, Russo V, Kerger J, Masucci G, Jager E, De Greve J, Atzpodien J, Brasseur F, Coulie PG, van der Bruggen P, Boon T. Tumor regressions observed in patients with metastatic melanoma treated with an antigenic peptide encoded by gene MAGE-3 and presented by HLA-A1. Int J Cancer. 1999 Jan 18;80(2):219-30. doi: 10.1002/(sici)1097-0215(19990118)80:23.0.co;2-s.

  PMID: 9935203 BACKGROUND

• Germeau C, Ma W, Schiavetti F, Lurquin C, Henry E, Vigneron N, Brasseur F, Lethe B, De Plaen E, Velu T, Boon T, Coulie PG. High frequency of antitumor T cells in the blood of melanoma patients before and after vaccination with tumor antigens. J Exp Med. 2005 Jan 17;201(2):241-8. doi: 10.1084/jem.20041379.

  PMID: 15657293 BACKGROUND

• Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L, Verweij J, Van Glabbeke M, van Oosterom AT, Christian MC, Gwyther SG. New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst. 2000 Feb 2;92(3):205-16. doi: 10.1093/jnci/92.3.205.

  PMID: 10655437 BACKGROUND

MeSH Terms

Conditions

Melanoma

Interventions

montanide ISA 51; ProMune

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

Results Point of Contact

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

jskipper@lcr.org

12124501539

Study Officials

• Nicolas VanBaren, MD

  Ludwig Institute for Cancer Research

  STUDY CHAIR

• Thierry BOON, PhD

  Ludwig Institute for Cancer Research

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: The protocol planned the inclusion of 2 cohorts, each of them including 14 patients, with metastatic cutaneous melanoma, with at least one detectable metastasis (grades AJCC 2002 III N2b to N3, grades IV M1a, M1b, and M1c without elevation of the LDH rate and without central nervous system toxicity).

Study Record Dates

• First Submitted: September 1, 2005
• First Posted: September 5, 2005
• Study Start: January 1, 2005
• Primary Completion: November 30, 2007
• Study Completion: March 12, 2009
• Last Updated: October 10, 2022
• Results First Posted: April 7, 2022

Record last verified: 2022-10

Data Sharing

• IPD Sharing: Will not share

Locations

BE (2)