- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00975520
Neurotropic Melanoma of the Head and Neck (RTN2)
A Randomised Trial of Post-operative Radiation Therapy Following Wide Excision of Neurotropic Melanoma of the Head and Neck
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Background Melanoma is a serious and common malignancy in Australia. It is the third most common cancer in Australia and approximately 1000 Australians will die of the disease each year.At least a quarter of these will be patients under the age of 40 years.
Neurotropism, defined as invasion by melanoma of peripheral neural tissue, is a feature of the disease that may predispose towards a high local recurrence rate. Local recurrence, particularly in the head and neck region often requires more extensive, potentially morbid surgery. Neurotropism is especially likely to occur in desmoplastic melanoma where it may be as high as 40 - 60%.6-8 Desmoplastic melanoma tends to occur in a slightly older age group than conventional types of melanoma and most often occurs in the head and neck region in individuals with chronic sun damage.
The management of localised neurotropic melanoma has traditionally been with surgery. Recommendations are that surgical margins should be at least 2 cm.There are some patients where this margin is not achievable due to the location of the tumour close to important anatomical structures. Uncontrolled studies suggest that radiation therapy may reduce the risk of local recurrence in those patients although there are no randomised trials to confirm this hypothesis.
Postoperative adjuvant radiation therapy has been shown in a randomised trial led from Australia, to reduce regional recurrence rates in nodal melanoma.There are no previously conducted randomised controlled trials addressing a similar question for neurotropic melanoma. The only reports are in relation to retrospective reviews that suggest a benefit for postoperative radiation therapy after surgery. It is unlikely that this trial will be done outside of Australia.
Hypotheses
- Radiation therapy after surgery for neurotropic melanoma improves local control.
- This can be achieved without a significant increase in treatment morbidity or reduction in quality of life.
Primary Objective
• To determine, in patients who have undergone surgery with curative intent for neurotropic melanoma, whether there is a difference in the rate and timing of local (in field) recurrence between patients who are treated with post-operative radiation therapy and those that are initially observed.
Secondary Objectives
- To determine, in these patients, whether there is a difference in progression-free survival, patterns of relapse and overall survival between patients treated with surgery alone and those treated by surgery plus adjuvant radiation therapy.
- To determine, in these patients, whether there is a difference in morbidity and quality of life between patients treated with surgery alone and those treated with surgery plus adjuvant radiation therapy
Methodology This is a 2-armed randomised controlled trial comparing surgery alone with surgery plus post-operative radiation therapy for patients with completely resected primary melanoma showing histological features of neurotropism. Patients who are eligible on the basis of the pathology of the completely excised melanoma will be offered the opportunity to take part in the trial. Those randomised to receive radiation therapy will be treated with a simple technique encompassing the surgical bed plus a margin within 3 months of surgery. The same regimen which was used in the nodal trial will be used in this study. Patients in the observation arm who subsequently recur in field may be offered further surgery followed by radiation therapy.
Randomisation Methods Patients will be randomised in the ratio of 1:1 between the two arms, radiation therapy and no radiation therapy. Allocation to the treatment arm will be stratified by institution and tumour site (head or neck) using randomly permuted blocks. Patients who are eligible on the basis of their pathology of excised melanoma will be offered the opportunity to take part in the trial. While males and females will both be considered equally for participation on the trial, there is no way of knowing if the ratio will be 1:1.
Study Type
Enrollment (Anticipated)
Phase
- Not Applicable
Contacts and Locations
Study Locations
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New South Wales
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Newcastle, New South Wales, Australia, 2310
- Calvary Mater Hospital
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North Sydney, New South Wales, Australia, 2060
- Melanoma Institute Australia / Royal Prince Alfred Hospital
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Westmead, New South Wales, Australia
- Westmead Hospital
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Wollongong, New South Wales, Australia
- Wollongong Hospital
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Queensland
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Herston, Queensland, Australia
- Royal Brisbane and Womens Hospital
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South Brisbane, Queensland, Australia, 4101
- Radiation Oncology Services - Mater Centre
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Toowoomba, Queensland, Australia
- Radiation Oncology Queensland (ROQ)
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Townsville, Queensland, Australia
- Townsville Cancer Centre
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Tugun, Queensland, Australia, 4224
- Genesis Care: Tugun
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Woolloongabba, Queensland, Australia, 4102
- Princess Alexandra Hospital
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South Australia
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Adelaide, South Australia, Australia, 5000
- Royal Adelaide Hospital
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Victoria
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East Melbourne, Victoria, Australia, 8006
- Peter MacCallum Cancer Centre
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Melbourne, Victoria, Australia, 3004
- Alfred Hospital
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Norwich, United Kingdom, NR4 7UY
- Norfolk and Norwich University Hosptial, NHS Foundation Trust
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New York
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New York, New York, United States, 10065
- Memorial Sloan Ketttering
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Texas
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Houston, Texas, United States, 77030
- Md Anderson Cancer Center
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Aged 18 years or older
- Has provided written informed consent for participation in this trial
Histologically confirmed neurotropic primary melanoma
- Neurotropism is identified pathologically by the presence of melanoma cells around nerve sheaths (perineural invasion) or within nerves (intraneural invasion).
- Occasionally, the tumour itself may form neuroid structures (termed 'neural transformation'; this is also regarded as neurotropism)
- "normal"-looking nerves that appear to be "entrapped" within the tumour should not be regarded as neurotropism
- Tumour located above the clavicle and below the jaw or occiput (neck primary) or above the jaw/occiput (head primary)
- Complete macroscopic resection of all known disease
- No previous surgery for melanoma (other than complete macroscopic resection as stated above)(i.e. Not recurrent disease)
- No evidence of in-transit, nodal or distant metastases as determined by clinical examination, CT or MRI
- ECOG performance status score of 2 or less
- Life expectancy greater than 6 months
- Patients capable of childbearing are using adequate contraception
- Available for follow up
Exclusion Criteria:
- Women who are pregnant or lactating
- Intercurrent illness that will interfere with the radiation therapy such as immunosuppression due to medication or medical condition
- Clinical and/or MRI evidence of a named cranial or cervical nerve involvement by tumour
- Inability to localise surgical bed on CT scans and/or surgical margins (cm) not known
- Previous radical radiation therapy to the head and neck, excluding superficial radiation therapy to cutaneous SCC or basal cell carcinoma, which is not within or overlapping the tumour bed
- High risk for poor compliance with therapy or follow-up as assessed by investigator
- Patients with prior cancers, except: those diagnosed ≥ 5 years ago with no evidence of disease relapse and clinical expectation of relapse of less than 5%; prior successfully treated Level 1 cutaneous melanomas ≥ 2 years ago; or non-melanoma skin cancer; or carcinoma in situ of the cervix
- Albinism
- Participation in other clinical trials with the same primary endpoint
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Single
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: Radiation Therapy
Investigational Treatment
|
Patients randomised to the Investigational treatment arm, will receive adjuvant curative post-operative radiation therapy aiming to reduce the rate of local recurrence.
The recommended dose prescribed is 48 Gy in 20 fractions over 4 weeks.
Other Names:
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Other: Observation
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Patients will be observed after surgery until recurrence when they will be offered radiation therapy
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Time to local relapse
Time Frame: 5 years from the date of randomisation
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5 years from the date of randomisation
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Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Relapse free survival
Time Frame: 5 years from date of randomisation
|
5 years from date of randomisation
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Time to Relapse
Time Frame: 5 years from date of randomisation
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5 years from date of randomisation
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Overall survival
Time Frame: 5 years from date of randomisation
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5 years from date of randomisation
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Cancer specific survival
Time Frame: 5 years from date of randomisation
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5 years from date of randomisation
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Patterns of relapse
Time Frame: 5 years from date of randomisation
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5 years from date of randomisation
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Late Toxicity
Time Frame: 5 years from date of randomisation
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5 years from date of randomisation
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Collaborators and Investigators
Collaborators
Investigators
- Study Chair: Matthew Foote, Princess Alexandra Hospital
Publications and helpful links
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 01.09
- 2009/039 (Other Identifier: HREC)
- ACTRN12610000478011 (Registry Identifier: ANZCTR)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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