Metastatic MelanomaPhase 1/2NCT01723813
Peptide Vaccinations Plus GM-CT-01 in Melanoma
A Phase 1/2 study testing Tumor specific peptides: MAGE-3.A1 and / or NA17.A2, Galectin-3 inhibitor: GM-CT-01 systemic injections and Galectin-3 inhibitor: GM-CT-01 Peri-tumoral administration in people with Metastatic Melanoma, run by Cliniques universitaires Saint-Luc- Université Catholique de Louvain at 1 site in Belgium.
Trial summary
The purpose of this study is to determine whether the intravenous and/or GM-CT-01 administration can correct Tumor Infiltrating Lymphocytes (TIL) anergy and induce a more efficient and long-lasting anti-tumoral immune response following peptide vaccination. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Melanoma
- What is being tested?
- Tumor specific peptides: MAGE-3.A1 and / or NA17.A2, Galectin-3 inhibitor: GM-CT-01 systemic injections and Galectin-3 inhibitor: GM-CT-01 Peri-tumoral administration
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 6 participants
- Where
- 1 siteBelgium
- Study dates
- Apr 2012to 1 Apr 2015
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
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
- 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 value
- 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 amplification).
- 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 entry.
- Age ≥ 18 years.
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- 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 research.
- Signed informed consent from the patient must be obtained.
Who cannot join
- 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 enrollment.
- 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.
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- Active immunodeficiency disease or autoimmune disease (vitiligo is not an exclusion criterion).
- 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 treatment.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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
The purpose of this study is to determine whether the intravenous and/or GM-CT-01 administration can correct Tumor Infiltrating Lymphocytes (TIL) anergy and induce a more efficient and long-lasting anti-tumoral immune response following peptide vaccination.
Read the detailed description
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 drugs.
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.
- Conditions
- Metastatic Melanoma
- Being tested
- Tumor specific peptides: MAGE-3.A1 and / or NA17.A2, Galectin-3 inhibitor: GM-CT-01 systemic injections, Galectin-3 inhibitor: GM-CT-01 Peri-tumoral administration
- Keywords
- Immunotherapy, Tumor-specific peptides, GM-CT-01
- Medical subject headings
- Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Tumor specific peptides: MAGE-3.A1 and / or NA17.A2Biological
Each peptide will be given at a dose of 300 µg in 1 ml of sodium chloride 0.9%, every 3 weeks on 6 occasions, and will be administered at one site in arm or thigh, 20% of the dose intradermally and 80% of the dose subcutaneously.
Galectin-3 inhibitor: GM-CT-01 systemic injectionsBiological
Systemic injection of GM-CT-01: GM-CT-01 will be administered by slow intravenous infusions at a dose of 280 mg/m2, on days +3, +6, +9, +12, +15, +18 after each of the 3rd, 4th, 5th and 6th vaccination.
Galectin-3 inhibitor: GM-CT-01 Peri-tumoral administrationBiological
GM-CT-01 will be injected peri-tumoral at a dose of 100 µg per tumor injected, on days +3, +6, +9, +12, +15, +18 after each of the 3rd, 4th, 5th and 6th vaccination. If a patient has one or two superficial metastases at day 43 of the treatment, one of these lesions will be treated. If a patient has more than two superficial metastases at day 43, two of these lesions will be treated.
| Study group | Role | What they receive |
|---|---|---|
| Group 1 : peptides + GM-CT-01 IV | Experimental | Tumor specific peptides: MAGE-3.A1 and / or NA17.A2 plus Galectin-3 inhibitor: GM-CT-01 systemic injections Receives: Biological: Tumor specific peptides: MAGE-3.A1 and / or NA17.A2; Biological: Galectin-3 inhibitor: GM-CT-01 systemic injections |
| Group 2 : peptides + GM-CT-01 IV+PT | Experimental | Tumor specific peptides: MAGE-3.A1 and / or NA17.A2 plus Galectin-3 inhibitor: GM-CT-01 systemic injections and Galectin-3 inhibitor: GM-CT-01 Peri-tumoral administration Receives: Biological: Tumor specific peptides: MAGE-3.A1 and / or NA17.A2; Biological: Galectin-3 inhibitor: GM-CT-01 systemic injections; Biological: Galectin-3 inhibitor: GM-CT-01 Peri-tumoral administration |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of participants with adverse events
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
Measured: 30 days after last administration of Study drugs
Response rate in both arms
Efficacy of the combination of a peptide vaccine and GM-CT-01 injections measures performed by CT-scan or MRI
Measured: Change from baseline at week 7 and week 20
Secondary outcomes (4)
Response rate in group 2 versus group 1
To determine whether addition of peri-tumoral injections of GM-CT-01 increase tumor response therefore response rate observed in group 1 will be compared with group 2
Measured: Change from baseline at week 7 and week 20
Time to Progression
patients will be followed every three months at consultation and with radiological examination, they will be assessed up to 100 weeks
Measured: From date of inclusion until the date of first documented progression or date of death from any cause, which ever came first, assessed up to 100 weeks
Overall Survival
patients will be followed every three months at consultation and with radiological examination, they will be assessed up to 100 weeks
Measured: From day of inclusion to date of death
Immunogenicity of the treatment
assessed at baseline and at week 20
Measured: Change from baseline at week 20
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Nov 2012 (estimated)
- Study startApr 2012
- Primary completion1 Apr 2015
- Study completion1 Apr 2015
Why it stopped: due to end of validity of peptide vaccine
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Metastatic MelanomaStudies of the same condition, open and under way.
- More trials run by Cliniques universitaires Saint-Luc- Université Catholique de LouvainThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 6 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Jean-Francois BAURAIN, MD, PhD, Principal investigator, Cliniques univeristaires Saint-Luc
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01723813
- Sponsor's protocol ID
- LUC 10-001
- Status last verified
- Mar 2019
- First submitted
- 28 Sep 2012
- Last updated
- 12 Mar 2019
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 Mar 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT01723813
- Acronym / sponsor ID
- LUC 10-001
- Conditions
- Metastatic Melanoma
- Keywords
- Immunotherapy, Tumor-specific peptides, GM-CT-01
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: due to end of validity of peptide vaccine
- Enrolment
- 6 participants (actual)
- Lead sponsor
- Cliniques universitaires Saint-Luc- Université Catholique de LouvainUniversity, hospital or other
- Study start
- Apr 2012
- Primary completion
- 1 Apr 2015 (actual)
- Study completion
- 1 Apr 2015 (actual)
- First posted
- 8 Nov 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to determine whether the intravenous and/or GM-CT-01 administration can correct Tumor Infiltrating Lymphocytes (TIL) anergy and induce a more efficient and long-lasting anti-tumoral immune response following peptide vaccination.
Detailed description
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 drugs.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Group 1 : peptides + GM-CT-01 IV | Experimental | Biological: Tumor specific peptides: MAGE-3.A1 and / or NA17.A2, Biological: Galectin-3 inhibitor: GM-CT-01 systemic injectionsTumor specific peptides: MAGE-3.A1 and / or NA17.A2 plus Galectin-3 inhibitor: GM-CT-01 systemic injections |
| Group 2 : peptides + GM-CT-01 IV+PT | Experimental | Biological: Tumor specific peptides: MAGE-3.A1 and / or NA17.A2, Biological: Galectin-3 inhibitor: GM-CT-01 systemic injections, Biological: Galectin-3 inhibitor: GM-CT-01 Peri-tumoral administrationTumor specific peptides: MAGE-3.A1 and / or NA17.A2 plus Galectin-3 inhibitor: GM-CT-01 systemic injections and Galectin-3 inhibitor: GM-CT-01 Peri-tumoral administration |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- 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 value
- 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 amplification).
- 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 entry.
Key exclusion criteria (11 listed)
- 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 enrollment.
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Tumor specific peptides: MAGE-3.A1 and / or NA17.A2Each peptide will be given at a dose of 300 µg in 1 ml of sodium chloride 0.9%, every 3 weeks on 6 occasions, and will be administered at one site in arm or thigh, 20% of the dose intradermally and 80% of the dose subcutaneously. | Biological | Group 1 : peptides + GM-CT-01 IV, Group 2 : peptides + GM-CT-01 IV+PT |
| Galectin-3 inhibitor: GM-CT-01 systemic injectionsSystemic injection of GM-CT-01: GM-CT-01 will be administered by slow intravenous infusions at a dose of 280 mg/m2, on days +3, +6, +9, +12, +15, +18 after each of the 3rd, 4th, 5th and 6th vaccination. | Biological | Group 1 : peptides + GM-CT-01 IV, Group 2 : peptides + GM-CT-01 IV+PT |
| Galectin-3 inhibitor: GM-CT-01 Peri-tumoral administrationGM-CT-01 will be injected peri-tumoral at a dose of 100 µg per tumor injected, on days +3, +6, +9, +12, +15, +18 after each of the 3rd, 4th, 5th and 6th vaccination. If a patient has one or two superficial metastases at day 43 of the treatment, one of these lesions will be treated. If a patient has more than two superficial metastases at day 43, two of these lesions will be treated. | Biological | Group 2 : peptides + GM-CT-01 IV+PT |
Primary outcome
Number of participants with adverse events
Time frame: 30 days after last administration of Study drugs
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
Response rate in both arms
Time frame: Change from baseline at week 7 and week 20
Efficacy of the combination of a peptide vaccine and GM-CT-01 injections measures performed by CT-scan or MRI
4 secondary outcomes
Response rate in group 2 versus group 1
Time frame: Change from baseline at week 7 and week 20
Time to Progression
Time frame: From date of inclusion until the date of first documented progression or date of death from any cause, which ever came first, assessed up to 100 weeks
Overall Survival
Time frame: From day of inclusion to date of death
Immunogenicity of the treatment
Time frame: Change from baseline at week 20
Results and safety
The study was stopped early (reason given: due to end of validity of peptide vaccine). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Mar 2019.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jean-Francois BAURAIN, MD, PhD principal investigator
Cliniques univeristaires Saint-Luc
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Tumor specific peptides: MAGE-3.A1 and / or NA17.A2, Galectin-3 inhibitor: GM-CT-01 systemic injections and Galectin-3 inhibitor: GM-CT-01 Peri-tumoral administration in people with Metastatic Melanoma, run by Cliniques universitaires Saint-Luc- Université Catholique de Louvain at 1 site 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 13 inclusion and 11 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 12 Mar 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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?
The study was stopped early (reason given: due to end of validity of peptide vaccine). Results are not available in the source record.
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 participants with adverse events (time frame: 30 days after last administration of Study drugs). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 12 Mar 2019.