Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Neurotropic Melanoma of the Head and Neck (RTN2)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00975520
Recruitment Status : Active, not recruiting
First Posted : September 11, 2009
Last Update Posted : March 18, 2020
Sponsor:
Collaborator:
Trans-Tasman Radiation Oncology Group (TROG)
Information provided by (Responsible Party):
Melanoma and Skin Cancer Trials Limited

Tracking Information
First Submitted Date  ICMJE September 10, 2009
First Posted Date  ICMJE September 11, 2009
Last Update Posted Date March 18, 2020
Study Start Date  ICMJE September 2009
Estimated Primary Completion Date January 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 8, 2009)
Time to local relapse [ Time Frame: 5 years from the date of randomisation ]
Original Primary Outcome Measures  ICMJE
 (submitted: September 10, 2009)
Time to local relapse [ Time Frame: Time from randomisation to time of diagnosis of local relapse ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 8, 2009)
  • 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 ]
Original Secondary Outcome Measures  ICMJE
 (submitted: September 10, 2009)
  • Relapse free survival [ Time Frame: Time from randomisation to development of relpase at any site ]
  • Time to Relapse [ Time Frame: Time from randomisation to the development of relapse at any site (local, regional and distant metastases). ]
  • Overall survival [ Time Frame: Time from randomisation until death from any cause ]
  • Cancer specific survival [ Time Frame: Time from registration until death from melanoma ]
  • Patterns of relapse [ Time Frame: Time from registration to relpase ]
  • Late Toxicity [ Time Frame: Time from randomisation to end of trial ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Neurotropic Melanoma of the Head and Neck
Official Title  ICMJE A Randomised Trial of Post-operative Radiation Therapy Following Wide Excision of Neurotropic Melanoma of the Head and Neck
Brief 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. 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

  1. Radiation therapy after surgery for neurotropic melanoma improves local control.
  2. 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  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Melanoma
Intervention  ICMJE
  • Other: Observation
    Patients will be observed after surgery until recurrence when they will be offered radiation therapy
    Other Name: Surgery Alone
  • Radiation: Radiation Therapy
    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 Name: RT, radiotherapy
Study Arms  ICMJE
  • Active Comparator: Radiation Therapy
    Investigational Treatment
    Intervention: Radiation: Radiation Therapy
  • Observation
    Observation
    Intervention: Other: Observation
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Estimated Enrollment  ICMJE
 (submitted: September 10, 2009)
100
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE January 2021
Estimated Primary Completion Date January 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00975520
Other Study ID Numbers  ICMJE 01.09
2009/039 ( Other Identifier: HREC )
ACTRN12610000478011 ( Registry Identifier: ANZCTR )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Plan Description: Not sharing IPD
Responsible Party Melanoma and Skin Cancer Trials Limited
Study Sponsor  ICMJE Melanoma and Skin Cancer Trials Limited
Collaborators  ICMJE Trans-Tasman Radiation Oncology Group (TROG)
Investigators  ICMJE
Study Chair: Matthew Foote, Oncologist Princess Alexandra Hospital
PRS Account Melanoma and Skin Cancer Trials Limited
Verification Date March 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP