Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
NCT-2007-11-02-1002
Study information
Scientific title
Phase I trial of RAB38/NY-MEL-1(50-58) peptide combined with Montanide® ISA-51 in HLA-A*0201 patients with stage III/IV malignant melanoma
Acronym
RAB38
Study hypothesis
In contrast to other solid tumours, immunology plays a major role in malignant melanoma. RAB38/NY-MEL-1 is a tumour antigen, which is exclusively expressed in melanocytes. Furthermore, antibodies against this polypeptide have exclusively been identified in the sera of patients with malignant melanoma. Therefore, the RAB38/NY-MEL-1 protein is an interesting target for immunisation strategies in these patients. Patients can be included in this study after failure or intolerance of standard chemotherapy. For these patients, other salvage treatments are not yet established and no therapy has been proven to be superior to best supportive care alone. The RAB38/NY-MEL-1 polypeptide has not been used in vaccination protocols before. Other tumour antigens (e.g. NY-ESO 1) have been studied in similar studies, where single patients responded to the vaccination and achieved regression of the tumour manifestations. The tolerability of the vaccination protocols described before was good and severe toxic side effects did not occur in most studies. Within this study, 9 patients with advanced malignant melanoma will be vaccinated with the RAB38/NY-MEL-1(50-58) peptide mixed with Montanide® ISA-51 as an adjuvant.
Ethics approval
Local medical ethics committee (Ethikkommission der Medizinischen Fakultät Heidelberg) gave approval on the 27th March 2008 (ref: AFmo-278/2007)
Study design
Open-label, single arm, phase I study
Primary study design
Interventional
Secondary study design
Non randomised controlled trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Not available in web format, please use the contact details below to request a patient information sheet
Condition
Malignant melanoma stage III/IV
Intervention
Patients will receive RAB38/NY-MEL-1 peptide 400 µg mixed with 0.5 mL of Montanide® ISA-51 by intradermal injections, every 3 weeks (weeks 1, 4, 7, 10, 13 and 16) for six doses. Patients without disease progression in the absence of dose-limiting toxicity will receive continued treatment starting 3 weeks after the last injection. Treatment courses will be continued until tumour progression. No dose adjustments during the study are planned.
Intervention type
Drug
Phase
Phase I
Drug names
RAB38/NY-MEL-1(50-58) peptide, Montanide® ISA-51
Primary outcome measure
1. Toxicities and adverse events (AE) defined by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE)
2. RAB38/NY-MEL-1 specific cellular and humoral immune responses (CD8 T cell responses, serum antibody responses)
Measured at baseline, week 1, 4, 7, 10, 13, 16 and 19.
Secondary outcome measures
Tumour response will be assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST), measured at week 19.
Overall trial start date
01/07/2008
Overall trial end date
30/06/2009
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. Histologically confirmed metastatic, measurable malignant melanoma stage III/IV who have declined, failed or completed standard therapy
2. Tumour expression of RAB38/NY-MEL-1 by reverse transcriptase-polymerase chain reaction (RT-PCR) analysis
3. HLA-A2 positive
4. Expected survival of at least six months
5. Karnofsky performance scale greater than or equal to 60%
6. Full recovery from surgery
7. Within the last 2 weeks prior to study day 1 the following laboratory parameters, which should be within the ranges specified:
7.1. Absolute neutrophil count (ANC) greater than or equal to 1000/mm^3
7.2. Platelets greater than or equal to 80.000/mm^3
7.3. Creatinine less than or equal to 1.5 mg/L
7.4. Alanine aminotransferase (ALT), aspartate aminotransferase (AST) and total bilirubin all less than 2.5 x upper limit of normal (ULN)
8. Age greater than or equal to 18 years
9. Able and willing to give valid written inform consent
10. Both genders will be included
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
9 patients
Participant exclusion criteria
1. Clinically significant heart disease (New York Heart Association [NYHA] class III or IV)
2. Other serious illnesses, e.g., serious infections requiring antibiotics or bleeding disorders
3. Patients with serious intercurrent illness, requiring hospitalisation
4. Patients taking immunosuppressive drugs such as systemic corticosteroids. Topical or inhalational steroids are permitted.
5. Known human immunodeficiency virus (HIV) positivity
6. Other active malignancy within 1 year prior to entry into the study, except for treated non-melanoma skin cancer and cervical carcinoma in situ
7. Mental impairment that may compromise the ability to give informed consent and comply with the requirements of the study
8. Lack of availability for immunological and clinical follow-up assessments
9. Participation in chemotherapy, radiation therapy, or any other clinical trial involving another investigational agent within 4 weeks prior to enrolment
10. Pregnancy or breastfeeding
11. Women of childbearing potential: refusal or inability to use effective means of contraception
12. History of severe allergic reactions to vaccines or unknown allergens
Recruitment start date
01/07/2008
Recruitment end date
30/06/2009
Locations
Countries of recruitment
Germany
Trial participating centre
Medical Oncology
Heidelberg
69120
Germany
Sponsor information
Organisation
University Hospital Heidelberg (Universitätsklinikum Heidelberg) (Germany)
Sponsor details
c/o Mrs. Irmtraut Guerkan
Im Neuenheimer Feld 672
Heidelberg
69120
Germany
Sponsor type
Hospital/treatment centre
Website
Funders
Funder type
Research organisation
Funder name
National Center for Tumor Diseases (Germany)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Funder name
Ludwig Institute for Cancer Research (LICR) (USA)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Basic results (scientific)
Publication list