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Phase I/II Study of Peptide Vaccination Associated With GM-CT-01, a Galactomannan Oligomer That Inhibits Galectin-3, in Patients With Advanced Metastatic Melanoma

Phase 1/Phase 2
18 Years
Open (Enrolling)
Metastatic Melanoma

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Trial Information

Phase I/II Study of Peptide Vaccination Associated With GM-CT-01, a Galactomannan Oligomer That Inhibits Galectin-3, in Patients With Advanced Metastatic Melanoma

Human cancers express tumor antigens that can be targeted by cytolytic T lymphocytes (CTL).
These antigens consist of a small peptide, derived from endogenous proteins, that is
presented at the cancer cell's surface by an HLA class I molecule. Such antigenic peptides,
including MAGE-3.A1 and NA17.A2, have been tested in experimental therapeutic vaccines to
elicit CTL responses in cancer patients, mainly with metastatic melanoma. Up to now, only
rare tumor responses have been observed.

Tumor resistance to CTL killing is the most likely explanation for the poor effectiveness of
cancer vaccines. This resistance is probably acquired by the tumor during its development
and selected by its repetitive challenge with spontaneous anti-tumoral immune responses.
Recently, we have identified a novel mechanism causing anergy of tumor-associated T
lymphocytes, and established new approaches to correct this anergy in vitro. Galectin-3,
secreted by tumor cells, appears to inhibit CTL function the co-localization of the T cell
receptor and the cluster of differentiation 8 coreceptor. Importantly, this functional
defect is restored when anergic T cells are incubated with galectin-3 inhibitors such as the
disaccharides lactose and N-acetyllactosamine, and the polysaccharide GM-CT-01. GM-CT-01 is
a vegetal galactomannan oligomer, currently under clinical investigation in several types of
solid malignancies for its capacity to inhibit galectins and to synergize with chemotherapy

Our observations suggest that treatment of cancer patients with GM-CT-01 could correct TIL
anergy and induce a more efficient and long-lasting anti-tumoral immune response following
peptide vaccination.

Inclusion Criteria:

- Patients with histologically proven cutaneous melanoma at one of the following
American Joint Committee on Cancer stages : Regional metastatic disease (any T; N2c
or N3; M0), no amenable to curative treatment by surgery or isolated limb
perfusion.Distant metastatic disease (any T; any N; M1a, M1b or M1c*).*except
uncontrolled brain metastasis and except Lactate dehydrogenase >1.5 upper normal

- HLA-A1 or HLA-A2 (by serology or molecular biology)

- At least one of the two following conditions:

MAGE-3 gene expression by the tumor if patient is HLA-A1 NA17 gene expression by the tumor
if patient is HLA-A2 (determined by reverse transcription and polymerase chain reaction

- Measurable Disease. Patients must have at least 1 measurable metastasis at study
entry for all patients. In addition, patients candidates for enrollment in Group 2
who will receive peri-tumoral injections of GM-CT-01 must have at least 1 superficial
metastasis (cutaneous, subcutaneous or superficial lymph node metastasis, with its
largest diameter equal to or greater than 5, 5, or 10 mm, respectively) at study

- Age ≥ 18 years.

- Karnofsky Performance status ≥70 or WHO performance status of 0 or 1

- Expected survival of at least 6 months.

- Laboratory values :

Platelet count ≥100x103/μL Leukocyte count ≥ 3x103/μL Hemoglobin ≥ 9 g/dL Aspartate
transaminase and Alanine transaminase ≤ 2 times upper normal value Serum creatinine ≤1.5
times upper normal value Total bilirubin ≤ 1.5 times upper normal value Lactate
dehydrogenase ≤ 1.5 times upper normal value

- Viral serology : negative antibodies for Hepatitis C Virus & HIV; negative antigens
for Hepatitis B Virus.

- Patient should agree to perform biopsies and blood collections for translational

- Signed informed consent from the patient must be obtained.

Exclusion Criteria:

- Uncontrolled brain or central nervous system metastasis.

- Previous treatment for the melanoma within 6 weeks from inclusion, with any reagent
known to modulate the immune system such as a cancer vaccine, interferon-alpha,
interleukins or anti-CTLA-4 antibodies.

- Previous chemotherapy, radiotherapy, corticotherapy, or other immune suppressive
therapy within 4 weeks from inclusion.

- Clinically significant cardiovascular disease (including cardiac insufficiency New
York Heart Association grade III and IV, unstable angina, arrythmia, myocardial
infarction, symptomatic congestive heart failure) in the past 12 months before

- 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 in the study, except for treated
non-melanoma skin cancer and in situ cervical carcinoma.

- Active immunodeficiency disease or autoimmune disease (vitiligo is not an exclusion

- 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.

- Subject pregnant or breastfeeding, or planning to become pregnant within 6 months
after the end of treatment.

- Subject (male or female) not willing to use highly effective methods of contraception
(per institutional standard) during treatment and for 6 months after the end of

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Number of participants with adverse events

Outcome Description:

Change from baseline in adverse events will be recorded at each patient's visit and up to 30 days after last administration of study drugs. Measurements will use the Common Toxicity Criteria for Adverse Effects 4,0 scale

Outcome Time Frame:

30 days after last administration of Study drugs

Safety Issue:


Principal Investigator

Jean-Francois BAURAIN, MD, PhD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Cliniques univeristaires Saint-Luc


Belgium: Federal Agency for Medicinal Products and Health Products

Study ID:

LUC 10-001



Start Date:

April 2012

Completion Date:

April 2015

Related Keywords:

  • Metastatic Melanoma
  • Immunotherapy
  • Tumor-specific peptides
  • GM-CT-01
  • Melanoma