Plain English Summary
Background and study aims
Melanoma is a type of skin cancer that is able to spread to other organs in the body. The most common sign of the disease is a new mole appearing or a change in appearance of an existing mole. At the moment, there isn’t a widely used treatment option for early stage melanoma patients after they have had their initial therapy that will help prevent the cancer reoccurring. Indeed, the disease coming back remains the biggest challenge in the management of early stage melanoma. This study is investigating the use of stimulators of the immune system, namely unmethylated CpG type-B oligodeoxynucleotide (CpG type B) and Granulocyte/Macrophage-Colony Stimulating Factor (GM-CSF). The researchers want to know whether these substances can improve the immune response in order to fight the melanoma.
Who can participate?
Adults diagnosed with melanoma
What does the study involve?
Participants are randomly allocated to one of five groups. Those in group 1 are given an injection of CpG type B seven days at the tumour excision site (that is the site where the tumour is about to be removed) before undergoing a sentinel node biopsy (an operation that determines whether a cancer has spread beyond the original tumour into the lymphatic system). Those in group 2 are given an injection of CpG type B at the tumour excision site seven days and two days before the sentinel node biopsy. Those in group 3 are given an injection of CpG type B and GM-CSF at the tumour excision site seven days and two days before the sentinel node biopsy. Those in group 4 are given an injection of saline at the tumour excision site seven days before the sentinel node biopsy. Those in group 5 are given an injection of saline at the tumour excision site seven days and two days before the sentinel node biopsy. All participants are followed up two days after the biopsy and again after seven days to assess their immune response.
What are the possible benefits and risks of participating?
A possible benefit of participating in this trial might be that the immune system can effectively fight the melanoma cells that remain in the body after surgery. The side effects of these treatments are mild (symptoms of fever may occur) and are often easy to control.
Where is the study run from?
VU University Medical Center (Netherlands)
When is the study starting and how long is it expected to run for?
August 2003 to July 2017
Who is funding the study?
Fritz Ahlqvist Foundation
Who is the main contact?
Professor Tanja de Gruijl
Trial website
Contact information
Type
Scientific
Primary contact
Prof Tanja de Gruijl
ORCID ID
http://orcid.org/0000-0003-1464-8978
Contact details
VU University medical center – Cancer Center Amsterdam
Room CCA2.44
De Boelelaan 1117
Amsterdam
1081 HV
Netherlands
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
03.199
Study information
Scientific title
Immune response in the sentinel node in melanoma patients after the pre-operative administration of immune modulators GM-CSF and / or CpG 7909
Acronym
Study hypothesis
It is expected that local administration of CpG 7909 around the primary tumor site in melanoma patients will result in an increased size of the sentinel lymph node (SLN) and we expect to see higher frequencies and activations states of DC and T cells due to the production of Th-1 type cytokines (IL-12, IL-2, IFN-γ, IFN-α).
The researchers also expect to see an increase in specific cytotoxic T-cells under the influence of both CpG 7909 and GM-CSF in the tumor positive SLN since CpG and GM-CSF can probably enhance the response against specific tumor antigens more effectively when tumor cells are present in the lymph nodes.
Ethics approval
Institutional Review Board of the VU University Medical Centre, 16/03/2004, ref: IRB00002991
Study design
Single-center single-blinded randomized and placebo (saline) controlled phase-II clinical trial
Primary study design
Interventional
Secondary study design
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Not available in web format, please use the contact details to request a patient information sheet (in Dutch)
Condition
Clinical stage I-II melanoma
Intervention
There are three treatment arms and two saline (placebo) controlled arms.
Treatment arm 1: Intradermal injection at the tumor excision site with 8 mg CpG-B (PF-3512676, formerly named CPG 7909, Coley Pharmaceutical Group, Wellesley, MA) 7 days prior to the sentinel node biopsy.
Treatment arm 2: Intradermal injection at the tumor excision site with 1 mg CpG-B, 7 and 2 days prior to the sentinel node biopsy.
Treatment arm 3: Intradermal injection at the tumor excision site with 1 mg CpG-B and 100µg GM-CSF (Leukine®, Berlex Laboratories Inc. Montville, NJ) 7 and 2 days prior to the sentinel node biopsy.
Placebo arm 1: Intradermal injection at the tumor excision site with saline (0.9% NaCl) 7 days prior to the sentinel node biopsy.
Placebo arm 2: Intradermal injection at the tumor excision site with saline (0.9% NaCl) 7 and 2 days prior to the sentinel node biopsy.
All patients are followed up at day 7 and day 14 (after the sentinel node biopsy).
Intervention type
Drug
Phase
Phase II
Drug names
1. Unmethylated CpG type-B oligodeoxynucleotide; PF-3512676 (cpg7909)
2. Granulocyte/Macrophage-Colony Stimulating Factor; Leukine
Primary outcome measure
Immune status in the sentinel lymph node (SLN), specifically DC activation state and melanoma antigen specific T cells, measured using flow cytometry, interferon (IFN) gamma Elispot and tetramer analysis on immune cells that are harvested from the SLN at the day of the biopsy. .
Secondary outcome measures
Systemic anti melanoma activity measured using flow cytometry, IFN gamma Elispot and tetramer analysis on peripheral mononuclear blood cells from day -7, 0 and 14 (day 0 is the day of the SLN biopsy).
Overall trial start date
01/08/2003
Overall trial end date
01/07/2017
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
Patients with histologically proven primary melanoma, who are eligible for a SLN biopsy.
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
52
Participant exclusion criteria
1. Treated with chemotherapy or immunotherapy in the last ten years
2. Autoimmune diseases
3. Congenital or acquired immunodeficiency
4. Use of immunosuppressive medications
Recruitment start date
01/06/2004
Recruitment end date
30/06/2007
Locations
Countries of recruitment
Netherlands
Trial participating centre
VU University Medical Center
De Boelelaan 1117
Amsterdam
1081 HV
Netherlands
Sponsor information
Organisation
VU University Medical Center
Sponsor details
De Boelelaan 1117
Amsterdam
1081 HV
Netherlands
Sponsor type
Hospital/treatment centre
Website
Funders
Funder type
Charity
Funder name
Fritz Ahlqvist Foundation
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Primary outcome; i.e. immune stutus SLN has been published in four papers.
Clinical follow-up will be published in separate paper in conjunction with an earlier clinical study (preceding 2004) in which, in a similar set-up, the effects of single administration of GM-CSF were studied (Vuysteke et al Cancer Res 2004).
Intention to publish date
30/10/2016
Participant level data
Not provided at time of registration
Basic results (scientific)
Publication list
1. 2007 results in www.ncbi.nlm.nih.gov/pubmed/17504997
2. 2008 results in www.ncbi.nlm.nih.gov/pubmed/18628468
3. 2015 results in www.ncbi.nlm.nih.gov/pubmed/25633713
4. 2016 results in www.ncbi.nlm.nih.gov/pubmed/26935057