Radiotherapy or Imiquimod in Complex Lentigo Maligna (RADICAL)

A Randomised Controlled Multicentre Trial of Imiquimod Versus Radiotherapy for Lentigo Maligna (LM) When Staged Surgical Excision With 5mm Margins is Not Possible, is Refused, or Fails

The purpose of this study is to investigate the effectiveness of using either radiotherapy (RT) or Imiquimod (ImiQ) to treat the Lentigo Maligna (LM), when surgery is not possible, is refused, or fails.

Study Overview

• Status: Completed
• Conditions: Lentigo Maligna
• Intervention / Treatment: Radiation: Radiotherapy; Drug: Imiquimod

Detailed Description

Surgery is the standard treatment for people diagnosed with LM. However for some people, it may not be possible due to the location of their LM lesion(s).

Currently, the Australian and New Zealand Melanoma Treatment Guidelines recommend radiotherapy for the treatment of LM however there is no clinical trial evidence for this and a trial is needed to prove which treatment is safer and more effective. Some clinicians may also recommend the use of a cream called Imiquimod. It is approved and widely used in Australia to treat solar keratosis, superficial basal cell carcinoma, external genital warts, and perianal warts. Although not currently licensed for treatment use in LM, there is some evidence to suggest that it is both safe and effective in treating LM.

This trial will scientifically evaluate and compare these two treatments in a controlled clinical setting.

The primary objective of this trial is to compare the rate of LM treatment failure and recurrence rate measured at 24 months (primary endpoint), and measured at 6, 12 months (secondary endpoints) following treatment with ImiQ or RT. For this study, treatment failure includes both the recurrence and persistence of LM, and is defined as the presence of LM cells within the original field of treatment confirmed by histopathology.

• Study Type: Interventional
• Enrollment (Actual): 126
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Newcastle, New South Wales, Australia, 2298
      • Calvary Mater Newcastle
    • North Sydney, New South Wales, Australia, 2060
      • Melanoma Institute Australia
    • Sydney, New South Wales, Australia, 2145
      • Westmead Hospital
    • Sydney, New South Wales, Australia, 2010
      • Skin and Cancer Foundation
    • Sydney, New South Wales, Australia
      • St Vincent's Hospital, Sydney
  • Queensland
    • Brisbane, Queensland, Australia, 4102
      • Princess Alexandra Hospital
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Royal Adelaide Hospital
  • Victoria
    • Melbourne, Victoria, Australia, 3004
      • The Alfred Hospital
• Brazil
  • São Paulo, Brazil
    • Hospital das Clinicas, University of Sao Paulo
• New Zealand
  • Auckland
    • Takapuna, Auckland, New Zealand, 0740
      • North Shore Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 120 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Aged 18 years or older.
2. A biopsy-proven LM. This includes previous treatment failures (not with imiquimod or RT) of LM that are diagnosed as biopsy-proven LM.
3. LM that is in a location amenable to treatment with imiquimod and radiotherapy.
4. Willing and able to comply with study requirements.
5. Written informed consent.

Exclusion Criteria:

1. Invasive melanoma.
2. Medical or psychiatric condition that compromises the ability of the patient to complete protocol treatment or follow-up assessments.
3. Patients who are pregnant or lactating. Women of child bearing potential must have a confirmed negative urine pregnancy test at study entry.
4. Life expectancy of less than 2 years.
5. Radiotherapy sensitivity syndrome

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Imiquimod; Topical imiquimod 5% cream; application to treatment area for 5 days/week for a total of 12 weeks; dispensed at baseline visit along with patient diary	Drug: Imiquimod; Other Names: Aldara
Experimental: Radiotherapy; Radiotherapy; treatment regimen determined by treating radiation oncologist and as per standard practice at local institution; treatment to commence within 8 weeks of randomisation	Radiation: Radiotherapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of patients experiencing LM treatment failure	Determined by systematic biopsy, 6 months following completion of treatment.	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cosmetic outcome 24 months after treatment or at treatment failure	Evaluated using photographs taken of LM lesion(s) during the study	24 months
LM treatment failure at 12 months and 24 months after the completion of treatment.	Determined by dermoscopy and/or Reflectance Confocal Microscopy and confirmed by biopsy	12 and 24 months
Incidence of invasive melanoma within treatment fields; a sub-study to evaluate the utility of reflectance confocal microscopy (RCM) compared with standard biopsy in diagnosing recurrence	Assessed at all time-points (6, 12 and 24 months post treatment). Time to failure of LM treatment and diagnosis with invasive melanoma within the treatment field was compared for each treatment arm using the log-rank test and Kaplan-Meier curves.	0-24 months
Quality of life using Skindex-16 questionnaire	Patient Reported outcomes were collected using the dermatology specific quality of life instrument Skindex-16 with additional questions specifically selected from the Skindex-29. The Skindex-16 instrument covers three domains: Symptoms, 4 items; Function, 5 items; Emotions, 7 items. Standard scoring of domain scores uses the average of the component items, transformed to 0-100 scale, with higher scores indicating a greater negative impact of skin disease on quality of life (function, emotions) and greater symptom experience.	0-24 months
Quality of life using Skindex-29 questionnaire	Due to the nature of this study it was decided to include additional questions from the Skindex-29 instrument (Q2, Q9 and Q18) as these questions address potential issues not covered by the Skindex-16.Similar to the Skindex-16, all responses are transformed to a linear scale of 100, with higher scores indicating more negative impact.	0-24 months

Collaborators and Investigators

• Sponsor: Melanoma and Skin Cancer Trials Limited
• Collaborators: Melanoma Institute Australia
• Investigators: Principal Investigator: Pascale Guitera, Melanoma Institute Australia

Study record dates

Study Major Dates

• Study Start (Actual): August 31, 2015
• Primary Completion (Actual): December 24, 2021
• Study Completion (Actual): March 30, 2023

Study Registration Dates

• First Submitted: March 10, 2015
• First Submitted That Met QC Criteria: March 16, 2015
• First Posted (Estimated): March 20, 2015

Study Record Updates

• Last Update Posted (Actual): June 20, 2024
• Last Update Submitted That Met QC Criteria: June 17, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Keywords: Radiotherapy; Imiquimod; Lentigo maligna
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms by Histologic Type; Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Hyperpigmentation; Pigmentation Disorders; Melanosis; Melanoma; Lentigo; Hutchinson's Melanotic Freckle; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Immunologic Factors; Adjuvants, Immunologic; Interferon Inducers; Toll-Like Receptor Agonists; Immunomodulating Agents; Imiquimod
• Other Study ID Numbers: 02.12