Condition category
Cancer
Date applied
18/07/2016
Date assigned
22/07/2016
Last edited
04/08/2016
Prospective/Retrospective
Retrospectively registered
Overall trial status
Ongoing
Recruitment status
No longer recruiting

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 measures

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

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

https://www.vumc.com/

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

Results - basic reporting

Publication summary

1. Molenkamp BG, van Leeuwen PA, Meijer S, Sluijter BJ, Wijnands PG, Baars A, van
den Eertwegh AJ, Scheper RJ, de Gruijl TD. Intradermal CpG-B activates both
plasmacytoid and myeloid dendritic cells in the sentinel lymph node of melanoma
patients. Clin Cancer Res. 2007 May 15;13(10):2961-9.
2. Molenkamp BG, Sluijter BJ, van Leeuwen PA, Santegoets SJ, Meijer S, Wijnands
PG, Haanen JB, van den Eertwegh AJ, Scheper RJ, de Gruijl TD. Local
administration of PF-3512676 CpG-B instigates tumor-specific CD8+ T-cell
reactivity in melanoma patients. Clin Cancer Res. 2008 Jul 15;14(14):4532-42.
3. Sluijter BJ, van den Hout MF, Koster BD, van Leeuwen PA, Schneiders FL, van de
Ven R, Molenkamp BG, Vosslamber S, Verweij CL, van den Tol MP, van den Eertwegh
AJ, Scheper RJ, de Gruijl TD. Arming the Melanoma Sentinel Lymph Node through
Local Administration of CpG-B and GM-CSF: Recruitment and Activation of
BDCA3/CD141(+) Dendritic Cells and Enhanced Cross-Presentation. Cancer Immunol
Res. 2015 May;3(5):495-505.
4. van den Hout MF, Sluijter BJ, Santegoets SJ, van Leeuwen PA, van den Tol MP,
van den Eertwegh AJ, Scheper RJ, de Gruijl TD. Local delivery of CpG-B and GM-CSF
induces concerted activation of effector and regulatory T cells in the human
melanoma sentinel lymph node. Cancer Immunol Immunother. 2016 Apr;65(4):405-15.

Publication citations

Additional files

Editorial Notes

04/08/2016: Added publications and changed ethics approval date from 16/03/2016 to 16/03/2004