Clinical trial NCT03138642: Mucosal Melanoma of Head and Neck in Intensity-modulated Radiotherapy Era
Official title: A Prospective Phase II Study in Patients With Mucosal Melanoma of Head and Neck in Intensity-modulated Radiotherapy Era
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Mucosal Melanoma
Keywords: mucosal melanoma
radiotherapy
Lead sponsor: Sun Yat-sen University
Sponsor class: OTHER
First posted: 2017-05-03
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: All the patients receive extended resection to primary tumor and post-surgery RT. The patients are prescribed a EQD2 of 70-77Gy to GTV (residual tumor), 65-70Gy to CTV1(high-risk regions including tumor bed and gross macroscopic residual tumor), 50-55Gy to CTV2(low-risk regions) using Intensity-modulated radiotherapy (IMRT)
Primary purpose: TREATMENT

Brief summary: In China, mucosal melanoma of head and neck (MMHN) account for 30-40% of all melanoma and the incidence is on the rise. The prognosis of MMHN is poor with the 5-year survival in a range between 20-30%. The evidence for the treatment of MMHN was weak since large-sample clinical researches are rare and no prospective clinical trial is reported. Surgery is the primary treatment modality for MMHN. However, it is difficult to extend the necessary surgery range for MMHN due to its limitation of being adjacent to the important anatomical structure in head and neck or by the considerations of the protection for organ function. As a result, the recurrence rate for surgery along was over 50%. Radiotherapy(RT) is the main approach for the multidisciplinary treatment for MMHN. Benlyazid et al. conclude the data from 13 centers and find that compared to surgery alone, the addition of post-surgery RT improve the survival; The 5-year locoregional failure rate for the surgery alone group and the RT+surgery group were 55.6% and 29.9%, respectively. Currently, the research into the prognosis factors is spare for the non-metastatic MMMHN received extended resection to primary tumor. It is necessary to undertake a prospective clinical research for MMHN in the endemic area to estimate efficacy and safety of primary surgery plus postoperative radiotherapy with or without adjuvant chemotherapy, as well as to recognize the risk distribution in this cohort of patients, provide the evidence to improve the stratification treatment strategies in the clinic.

Detailed description: All the patients enrolled are confirmed without any evidence of distant metastasis. All the patients receive extended resection to primary tumor and post-surgery RT. The patients are prescribed a EQD2 of 65-70Gy to CTV1 (high-risk regions including tumor bed), 50-55Gy to CTV2(low-risk regions) using Intensity-modulated radiotherapy (IMRT). The Prophylactic irradiation to upper neck is is decided by radiation physicians and given a EQD2 of 70-77Gy to CTVnd (clinically negative lymph nodes), 50-55Gy to CTVn2（neck nodal regions). If there is residual tumor, a EQD2 of 70-77Gy is prescribed to GTV. Adjuvant chemotherapy (for example, Temozolomide) is prescribed or not according the consideration of radiation physicians during RT or after RT. The clinical characteristics, radiation dose, chemotherapy regimen and the toxicities of are documented by the radiation physicians.

Eligibility criteria: Inclusion Criteria:

* Patients with histologically confirmed mucosal melanoma of head and neck (MMHN);
* Tumor staged as stages III/IVA (according to the American Joint Committee on Cancer 7th edition staging system) arising from head and neck according to the radiology and clinical exam;
* Prior local resection to primary tumor;
* Radiologically confirmed (MRI, CT or PET-CT if necessary) no regional lymph node present, nor any evidence of distant metastasis;
* Adequate marrow: white blood cell count of 4.0 × 109/L or more; absolute neutrophil of 2.0 × 109/L or more; haemoglobin concentrations of at least 90 g/L; platelet cell count of 100 × 109/L or more；
* Normal liver function test: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) \< 2.5×upper limit of normal (ULN)；
* Adequate renal function: creatinine clearance rate of more than 60 mL/min;
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1；
* Expected lifespan \> 3 months;
* Patients must be informed of the investigational nature of this study and give written informed consent；
* Patients must be consent to the follow-up till death, the study termination or the end of the study.

Exclusion Criteria:

* Patients with histologically or radiologically distant metastasis or recurrence of primary tumor;
* Any contraception to RT;
* History of previous RT or chemotherapy;
* Any severe previous or intercurrent disease, which may bring unacceptable risk or affect the compliance of the trial, for example, serious comorbidities, or had active lupus erythematosus or scleroderma, unstable cardiac disease needing treatment, chronic obstructive pulmonary disease exacerbation or other respiratory illness needing treatment, or an acute or fungal infection requiring treatmen);
* Prior malignancy within 5 years except adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer;
* Pregnancy or lactation;
* Unable or unwilling to the compliance of the study

Primary outcomes:
measure: Overall survival(OS)
timeFrame: 3 year
Secondary outcomes:
measure: Regional relapse-free survival(RRFS)
timeFrame: 3 Year
measure: Local recurrence-free survival(LRFS)
timeFrame: 3 Year
measure: Distant metastasis-free survival (DMFS)
timeFrame: 3 Year
measure: Number of participants with adverse events
timeFrame: 3 Year
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: LiXia Lu
state: Guangdong
Study officials:
affiliation: Sun Yat-sen University Cancer Center,China, Guangdong
name: LiXia Lu, M.D.
role: STUDY_CHAIR
affiliation: Sun Yat-sen University
name: LiXia Lu, M.D.
role: PRINCIPAL_INVESTIGATOR
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