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Malignant MelanomaPhase 1/2NCT00145158

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

A Phase 1/2 study testing 8 HLA-A2-restricted peptides and Montanide ISA51 and 8 HLA-A2-restricted peptides and CpG 7909 in people with Malignant Melanoma, run by Ludwig Institute for Cancer Research at 2 sites in Belgium.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Malignant Melanoma
What is being tested?
8 HLA-A2-restricted peptides and Montanide ISA51 and 8 HLA-A2-restricted peptides and CpG 7909
Could I receive a placebo?
No, everyone receives an active treatment
How many people
23 participants
Where
2 sitesBelgium
Study dates
Jan 2005to 12 Mar 2009
Phase
Phase 1/2
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

  • 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.
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  • 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
  • Serum creatinine ≤ 2.0 mg/dl or ≤ 177 μmol/l
  • Serum bilirubin ≤ 2.0 mg/dl or ≤ 34.2 μmol/l
  • ASAT and ALAT ≤ 2 x the normal upper limits
  • LDH ≤ the normal upper limit.
  • Viral tests:
  • HIV (human immunodeficiency virus): negative antibodies.
  • HBV (hepatitis B virus): negative antigens; antibodies may be positive.
  • HCV (hepatitis C virus): negative antibodies.
  • Age ≥ 18 years.
  • Able and willing to give valid written informed consent.

Who cannot join

  • 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.
  • Active immunodeficiency or autoimmune disease. Vitiligo was not an exclusion criterion.
  • 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.
Show all 9Show fewer
  • 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.

Belgium2 sites

  • Clinique Universitaires St-Luc

    Brussels, B-1200

  • Ludwig Institute for Cancer Research

    Brussels, B-1200

Other trials in Belgium

About this study

Official title: Phase I/II Study of Immunization With Multiple Peptides Mixed With the Immunological Adjuvant CpG 7909 or Montanide ISA51 in HLA-A2 Patients With Metastatic Cutaneous Melanoma

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.

Read the detailed description

Patients received six sequential immunizations with 8 peptides presented by HLA-A2 and mixed with either CpG 7909 or Montanide ISA51, at 2-week intervals. The 8 peptides were injected at 8 distinct injection sites. These peptides are the following: MAGE-1.A2, MAGE-3.A2, MAGE-4.A2, MAGE-10.A2, MAGE-C2.A2 (ALKD), and NA17.A2 (20% intradermally and 80% subcutaneously); NY-ESO-1.A2 and Tyrosinase.A2 (100% subcutaneously).

300 µg of each peptide (except MAGE-10.A2 150 µg) was mixed with 4 mg CpG 7909 (Cohort 1) or 0.5ml of Montanide ISA51 (Cohort 2). In Cohort 2, the Tyrosinase.A2 was administered without Montanide ISA51.

Tumor staging was performed before inclusion and at week 13. Peripheral Blood Lymphocytes (PBL) collections were performed before starting the treatment, and at weeks 3, 7 and 13. They provided the T lymphocytes for the immunological analysis.

At week 13, the PCR results of the pre-immune tumor biopsy must be available. Additional cycles of immunization, ONLY with the peptides expressed by the tumor, mixed with Montanide ISA51, will be proposed to patients without tumor progression requiring another treatment. A second cycle of 3 injections at 6-week intervals will be started at week 17, followed by a third cycle of 12 injections at 3-month intervals, starting at month 11. At any time, progression of the disease necessitating any treatment not allowed during the study will result in withdrawal.

The immune response may well be a limiting factor to the therapeutic efficacy of the vaccine. If this is the case, it then becomes crucial to understand why some patients develop a cytotoxic t-lymphocyte (CTL) response against the vaccine, while the majority of them do not. One possible explanation for the low frequency of clinical responses is that each injection of a single peptide has a low probability to provide the adequate stimulus to activate very rare CTL precursors. This probability should be increased if several peptides known to be undoubtedly associated with tumor regressions were used together to immunize patients.

Being tested
8 HLA-A2-restricted peptides and Montanide ISA51, 8 HLA-A2-restricted peptides and CpG 7909
Keywords
Melanoma, Vaccine, Peptide, Montanide
Medical subject headings
Melanoma

What participants receive

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

  • 8 HLA-A2-restricted peptides and Montanide ISA51Biological

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

Study groups in NCT00145158
Study groupRoleWhat they receive
Cohort 1: 8 HLA-A2-restricted peptides and CpG 7909ExperimentalPatients 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.
Receives: Biological: 8 HLA-A2-restricted peptides and CpG 7909
Cohort 2: 8 HLA-A2-Restricted Peptides and Montanide ISA51ExperimentalPatients 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.
Receives: Biological: 8 HLA-A2-restricted peptides and Montanide ISA51

What is being measured

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

  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.

    Measured: Week 13

Secondary outcomes (3)

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

    Toxicity was evaluated according to the National Cancer Institute (CTC Scale Version 3.0, published December 12, 2003).

    Dose limiting toxicity (DLT) is defined as:

    • Any Grade 3 hematological or non-hematological toxicity other than skin or flu-like symptoms
    • Any Grade 4 toxicity To be dose-limiting, an adverse event must be definitely, probably, or possibly related to the administration of the investigational agent.

    Measured: up to Week 13

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

    Tumor response was assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST). Tumor measurements were taken at screening and at the end of Cycle 1 in Week 13. Per RECIST, target lesions are categorized as follows: Complete Response (CR): Disappearance of all target lesions; 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: Week 13

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

    Gene expression was determined by RT-PCR on a pre-treatment tumor sample. The correlation of the induction of a CTL response against a defined antigen to the prior expression of the gene coding for this antigen by the tumor removed before vaccination was assessed.

    Measured: Week 13

Timeline

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

  1. First posted5 Sep 2005 (estimated)
  2. Study startJan 2005
  3. Primary completion30 Nov 2007
  4. Study completion12 Mar 2009

Why it stopped: Availability of Investigational agent

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 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Model description
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).
Masking
None (open label)
Enrolment
23 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00145158
Sponsor's protocol ID
LUD2003-007
Status last verified
Oct 2022
First submitted
1 Sep 2005
Last updated
10 Oct 2022
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 9935203

  • 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.

    PubMed 15657293

  • 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.

    PubMed 10655437

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing 8 HLA-A2-restricted peptides and Montanide ISA51 and 8 HLA-A2-restricted peptides and CpG 7909 in people with Malignant Melanoma, run by Ludwig Institute for Cancer Research at 2 sites in Belgium.

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 25 inclusion and 9 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: stopped early, as of the sponsor's last update on 10 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 Belgium. 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 combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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 7 Apr 2022). 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 Patients With Cytotoxic T-lymphocyte (CTL) Response to Individual Peptides After Immunization With a Combination of 8 Peptides and CpG 7909 or Montanide ISA51. (time frame: Week 13). 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 NCT00145158, which also lists 3 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 10 Oct 2022.

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