MelanomaRTN2NCT00975520
Neurotropic Melanoma of the Head and Neck
A study testing Observation and Radiation Therapy in people with Melanoma, run by Melanoma and Skin Cancer Trials Limited at 16 sites in 3 countries.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Melanoma
- What is being tested?
- Observation and Radiation Therapy
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 16 sitesin 3 countries
- Study dates
- Sep 2009to Mar 2023
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
16 sites in 3 countries.
16 sites in 3 countries
Australia13 sites
Royal Adelaide Hospital
Adelaide, South Australia, 5000
Peter MacCallum Cancer Centre
East Melbourne, Victoria, 8006
Royal Brisbane and Womens Hospital
Herston, Queensland
Alfred Hospital
Melbourne, Victoria, 3004
Calvary Mater Hospital
Newcastle, New South Wales, 2310
Melanoma Institute Australia / Royal Prince Alfred Hospital
North Sydney, New South Wales, 2060
Radiation Oncology Services - Mater Centre
South Brisbane, Queensland, 4101
Radiation Oncology Queensland (ROQ)
Toowoomba, Queensland
Townsville Cancer Centre
Townsville, Queensland
Genesis Care: Tugun
Tugun, Queensland, 4224
Westmead Hospital
Westmead, New South Wales
Wollongong Hospital
Wollongong, New South Wales
Princess Alexandra Hospital
Woolloongabba, Queensland, 4102
United States2 sites
MD Anderson Cancer Center
Houston, Texas, 77030
Memorial Sloan Ketttering
New York, New York, 10065
United Kingdom1 site
Norfolk and Norwich University Hosptial, NHS Foundation Trust
Norwich, NR4 7UY
About this study
Official title: A Randomised Trial of Post-operative Radiation Therapy Following Wide Excision of Neurotropic Melanoma of the Head and Neck
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. Uncontrolled studies suggest that this form of primary melanoma has a high risk of local recurrence and that postoperative radiation therapy may substantially reduce that risk. Patients who are eligible on the basis of the pathology of the 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. Radiation will commence within 3 months of surgery (maximum of 14 weeks from surgery to start of radiotherapy).
Read the 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.
- Conditions
- Melanoma
- Being tested
- Observation, Radiation Therapy
- Keywords
- Neurotropic, Melanoma, Observation, Radiation Therapy, Relapse
- Medical subject headings
- Melanoma, Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ObservationOther
Also called Surgery Alone
Patients will be observed after surgery until recurrence when they will be offered radiation therapy
Radiation TherapyRadiation
Also called RT, radiotherapy
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.
| Study group | Role | What they receive |
|---|---|---|
| Radiation Therapy | Active comparator | Investigational Treatment Receives: Radiation: Radiation Therapy |
| Observation | Other | Observation Receives: Other: Observation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time to local relapse
Measured: 5 years from the date of randomisation
Secondary outcomes (6)
Relapse free survival
Measured: 5 years from date of randomisation
Time to Relapse
Measured: 5 years from date of randomisation
Overall survival
Measured: 5 years from date of randomisation
Cancer specific survival
Measured: 5 years from date of randomisation
Patterns of relapse
Measured: 5 years from date of randomisation
Late Toxicity
Measured: 5 years from date of randomisation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Sep 2009 (estimated)
- Study startSep 2009
- Primary completionJan 2021
- Study completionMar 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for MelanomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- Melanoma and Skin Cancer Trials Limited
- Sponsor type
- University, hospital or other
- Collaborators
- Trans Tasman Radiation Oncology Group
- Responsible party
- Sponsor
- Investigators
- Matthew Foote, Study chair, Princess Alexandra Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00975520
- Sponsor's protocol ID
- 01.09
- Other IDs
- 2009/039, ACTRN12610000478011
- Acronym
- RTN2
- Status last verified
- Nov 2024
- First submitted
- 10 Sep 2009
- Last updated
- 27 Nov 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Not sharing IPD
Study at a glance
From the registry record, last updated by the sponsor on 27 Nov 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomised Trial of Post-operative Radiation Therapy Following Wide Excision of Neurotropic Melanoma of the Head and Neck
- ClinicalTrials.gov ID
- NCT00975520
- Acronym / sponsor ID
- RTN2 / 01.09
- Conditions
- Melanoma
- Keywords
- Neurotropic, Melanoma, Observation, Radiation Therapy, Relapse
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 50 participants (actual)
- Lead sponsor
- Melanoma and Skin Cancer Trials LimitedUniversity, hospital or other
- Collaborators
- Trans Tasman Radiation Oncology Group
- Study start
- Sep 2009
- Primary completion
- Jan 2021 (actual)
- Study completion
- Mar 2023 (actual)
- First posted
- 11 Sep 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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. Uncontrolled studies suggest that this form of primary melanoma has a high risk of local recurrence and that postoperative radiation therapy may substantially reduce that risk. Patients who are eligible on the basis of the pathology of the 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. Radiation will commence within 3 months of surgery (maximum of 14 weeks from surgery to start of radiotherapy).
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Radiation Therapy | Active comparator | Radiation: Radiation TherapyInvestigational Treatment |
| Observation | Other | Other: ObservationObservation |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- Aged 18 years or older
- Has provided written informed consent for participation in this trial
- Histologically confirmed neurotropic primary melanoma
- 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
Key exclusion criteria (9 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ObservationAlso: Surgery AlonePatients will be observed after surgery until recurrence when they will be offered radiation therapy | Other | Observation |
| Radiation TherapyAlso: RT, radiotherapyPatients 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. | Radiation | Radiation Therapy |
Primary outcome
Time to local relapse
Time frame: 5 years from the date of randomisation
6 secondary outcomes
Relapse free survival
Time frame: 5 years from date of randomisation
Time to Relapse
Time frame: 5 years from date of randomisation
Overall survival
Time frame: 5 years from date of randomisation
Cancer specific survival
Time frame: 5 years from date of randomisation
Patterns of relapse
Time frame: 5 years from date of randomisation
Late Toxicity
Time frame: 5 years from date of randomisation
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Nov 2024.
- Please visit this website for further trial specific informationLink provided by the sponsor.
- Individual participant dataSharing planned: No. Not sharing IPD
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Matthew Foote study chair
Princess Alexandra Hospital
16 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Observation and Radiation Therapy in people with Melanoma, run by Melanoma and Skin Cancer Trials Limited at 16 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 27 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 16 sites in Australia, United States, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Time to local relapse (time frame: 5 years from the date of randomisation). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Nov 2024.