Combined Local Immunotherapy and Radiotherapy in metastatic Melanoma

ISRCTN	ISRCTN26232057
DOI	https://doi.org/10.1186/ISRCTN26232057
Protocol serial number	N/A
Sponsor	St George's Healthcare NHS Trust (UK)
Funder	Application to Cancer Vaccine Institute (UK) in progress as of 17/09/2009.

Submission date: 17/09/2009
Registration date: 19/11/2009
Last edited: 12/12/2017

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Cancer

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Record updated in last year

Plain English summary of protocol

Not provided at time of registration

Contact information

Prof Angus Dalgleish
Scientific

Cellular and Molecular Medicine
Level 2 Jenner Wing
St George's University London
Cranmer Terrace
London
SW17 0RE
United Kingdom

Phone	+44 (0)20 8725 0809
Email	dalgleis@sgul.ac.uk

Study information

Primary study design	Interventional
Study design	Interventional single-arm single-centre trial
Secondary study design	Single-centre
Study type	Participant information sheet
Scientific title	Combined Local Immunotherapy and Radiotherapy in metastatic Melanoma: an interventional single-arm trial
Study acronym	CLIRM-1
Study objectives	Malignant melanoma lesions can be cleared using a combination of local immunotherapy (Toll-like receptor [TLR] agonists and interleukin-2 [IL-2]) and radiotherapy.
Ethics approval(s)	Wandsworth Research Ethics Committee, approval pending as of 17/09/2009
Health condition(s) or problem(s) studied	Metastatic melanoma
Intervention	All participants will receive the following treatments: 1. Aldara® cream applied four times weekly. Each sachet of 250 mg is sufficient to cover 20 square centimeters, so amount of cream used depends on the size of the lesion. 2. Intralesional injections of Proleukin® and Hiltonol®: 2.1. Proleukin® will be diluted to a concentration of 10 micrograms interleukin-2 per millilitre (10 ugml). Each lesion will have 100 microlitre injections, up to three in number depending on the size of the lesion. This will be performed three times weekly. 2.2. Hiltonol® is a 2 mg/ml solution and again, 100 microlitre injections will be made intralesionally, with a maximum of three injections per lesion, three times weekly. 3. Local radiotherapy The total duration will be one year if the treatment is effective, but we anticipate an average of 36 weeks, depending on the choice of radiotherapy schedule.
Intervention type	Drug
Phase	Not Applicable
Drug / device / biological / vaccine name(s)	Imiquimod (Aldara®), aldesleukin (Proleukin®), poly-ICLC (Hiltonol®)
Primary outcome measure(s)	Size of lesion All primary and secondary outcome measures will be measured formally at entry, after 1 month, 6 months and end of trial.
Key secondary outcome measure(s)	1. Toxicity associated with this treatment will be measured by the number of adverse and serious adverse events during treatment, and the number of injections delayed in case of excessive local reaction. 2. Frequency and latency of appearance of any new skin lesions local or distal to the treated area will be recorded 3. Levels of markers associated with tumour infiltrating lymphocytes and tumour associated macrophages will be estimated by real time polymerase chain reaction (RT-PCR) of material biopsied from the lesions 4. Systemic immune responses associated with this treatment will be assessed by analysis of serum levels of cytokines and white blood cell properties taken by blood sampling during treatment. All primary and secondary outcome measures will be measured formally at entry, after 1 month, 6 months and end of trial.
Completion date	31/12/2012

Eligibility

Participant type(s)	Patient
Age group	Adult
Sex	All
Target sample size at registration	30
Key inclusion criteria	1. Both males and females, aged 16 to 85 years 2. Patients who have one or more malignant skin tumours confirmed histologically at diagnosis 3. Patients with malignant skin tumours for whom other standard therapy options are no longer appropriate or have been refused by the patient 4. Life expectancy of at least 3-6 months 5. Patients with a WHO performance status of 0, 1 or 2 6. Patients who are informed of and are willing and able to comply with the home application of the Aldara® cream 7. Patients who are willing and able to comply with the investigational nature of the study and who have signed a written informed consent form 8. Patients who are willing to receive the number of intra-lesional injections and biopsies required to complete the study
Key exclusion criteria	1. Patients with unstable or severe current medical conditions or active, uncontrolled infection 2. Patients with psychological or sociological conditions, addictive disorders or family problems which would preclude compliance with the protocol 3. Patients undergoing therapy at study entry with other investigational agents that are directly immunosuppressive 4. Patients having procreative potential who are not using adequate contraception 5. Patients with untreated/uncontrolled brain tumours 6. Patients with brain tumours which have been treated but which have not been stable for 3 or more months 7. Patients with known hypersensitivity to Hiltonol®, IL-2, Aldara®, cyclophosphamide (for patients 16 30) or any of the excipients 8. Any condition, which, in the opinion of the investigator might interfere with the safety of the patient or evaluation of the study objectives
Date of first enrolment	01/01/2010
Date of final enrolment	31/12/2012

Locations

Countries of recruitment

United Kingdom
England

Study participating centre

St George's University London

London
SW17 0RE
United Kingdom

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Participant information sheet	Participant information sheet	11/11/2025	11/11/2025	No	Yes

Editorial Notes

12/12/2017: No publications found in PubMed, verifying study status with principal investigator.