Peptide Vaccination Associated With Tumoral Immunomodulation in Patients With Advanced Metastatic Melanoma
|ClinicalTrials.gov Identifier: NCT01191034|
Recruitment Status : Unknown
Verified August 2010 by Cliniques universitaires Saint-Luc- Université Catholique de Louvain.
Recruitment status was: Recruiting
First Posted : August 30, 2010
Last Update Posted : August 30, 2010
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. The precise molecular mechanisms of tumor resistance remain unknown. The observation that tumor-infiltrating lymphocytes (TIL) purified from melanoma metastases can recognize and kill autologous tumor cells in vitro, whilst they seem unable to control tumor growth in vivo, suggests that this resistance is hosted by the tumor environment, rather than being the result of a generalized immune suppression.
The investigators have developed a murine model of cutaneous graft rejection that mimics the situation in melanoma. Female CBA mice do not reject syngeneic male skin grafts, even though they mount a spontaneous CTL response against H-Y, a male specific minor histocompatibility antigen, following grafting. The investigators have tested various experimental procedures aimed at inducing effective graft rejection in these mice. This was obtained with a combination of IFN-α, IL-2, GM-CSF, each administered separately under the skin graft, associated with topical applications of imiquimod. All these agents are available as registered drugs. Based on this murine model of cutaneous allograft rejection, the investigators postulate that local immunomodulation with this combination can trigger an effective tumor rejection process, and induce a more efficient and long-lasting anti-tumoral immune response following peptide vaccination.
|Condition or disease||Intervention/treatment||Phase|
|Metastatic Melanoma||Drug: Vaccine MAGE-3.A1 peptide, or the NA17.A2 peptide + IL-2, IFN-α and GMCSF, Imiquimod.||Phase 1 Phase 2|
Patients will receive the following treatments:
The vaccine will be the MAGE-3.A1 and/or the NA17.A2 peptide, matching the patient's HLA type and the gene expression of his tumor. If both antigens are expressed, then the patient will receive both peptides.
- Local treatment with a combination of immunomodulatory drugs:
This treatment will combine peritumoral injection of IL-2, IFN-α and GM-CSF (6000 IU, 100.000 IU and 300 ng per tumor injected, respectively), as well as topical application of imiquimod (applied during 24h). The peritumoral injections of cytokines will be given on days +2,+3,+4,+7,+8 and +9, and the Aldara® cream will be applied on days +2 and +7 following vaccines 3 and 4. One or 2 cutaneous lesions will be treated, if there are 2 or more such lesions present at day 29 of the treatment, respectively.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||21 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase I/II Study of Peptide Vaccination Associated With Tumoral Immunomodulation With Proinflammatory Cytokines and Imiquimod in Patients With Advanced Metastatic Melanoma|
|Study Start Date :||August 2010|
|Estimated Primary Completion Date :||August 2011|
|Estimated Study Completion Date :||August 2012|
Drug: Vaccine MAGE-3.A1 peptide, or the NA17.A2 peptide + IL-2, IFN-α and GMCSF, Imiquimod.
The vaccine will be either the MAGE-3.A1 peptide, or the NA17.A2 peptide, or both,matching the patient's HLA type and the gene expression of his tumor. If both antigens are expressed, then the patient will receive both peptides.
This treatment will combine subcutaneous peritumoral injections of IL-2, IFN-α and GMCSF,as well as topical applications of imiquimod.
- To determine whether peptide vaccination associated with local peritumoral treatment with a combination of interleukin-2, interferon-alpha, granulocyte-macrophage colony stimulating factor, and imiquimod, induces tumor responses. [ Time Frame: week 11 day 71 ]Tumor response will be assessed in accordance with the Modified RECIST version 1.1
- To document the toxicity of treatment [ Time Frame: at each visit ]
Laboratory tests, vital sign measurements, physical exams and patient queries will be performed to detect new abnormalities and deteriorations of any pre-existing conditions.
All clinically significant abnormalities and deteriorations should be recorded in the Case Report Forms as Adverse Events and graded according to the National Cancer Institute CTCAE v3.0.
- To document whether this association induces cytolytic T lymphocyte responses to the vaccine antigens [ Time Frame: at week 11, day 71 ]CTL responses will be assessed by comparing either the anti-MAGE-3.A1 or the anti- NA17.A2 CTLp frequency in the pre- and post-immune blood of patients vaccinated with the respective antigen.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01191034
|Contact: Baurain Jean-François, MD, PhD||+32 2 764 firstname.lastname@example.org|
|Contact: Van Baren Nicolas, MD, PhD||+32 2 764 email@example.com|
|Cliniques Universitaires Saint-Luc||Recruiting|
|Bruxelles, Belgium, 1200|
|Contact: Baurain Jean-François, MD,PhD +32 2 764 5471 firstname.lastname@example.org|
|Contact: VanBaren Nicolas, MD,PhD +32 2 764 7508 email@example.com|
|Principal Investigator: Baurain Jean-François, MD,PhD|
|Principal Investigator:||Baurain Jean-Francois, MD, PhD||Cliniques universitaires Saint-Luc|