Protocol of Clinical Trial of EAFO 2012: Adjuvant Therapy of Skin Melanoma With Use of Alpha Interferon and Naderin
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 278
- 主要终点
- Recurrence-free survival
研究概览
简要总结
The goal of this clinical trial is to learn if adding alpha interferon to standard treatment works to prevent skin melanoma from coming back after surgery. The study will also learn if different doses of alpha interferon work better than others.
The main questions it aims to answer are:
- Does alpha interferon help people with melanoma live longer without the cancer returning?
- Does a higher dose of alpha interferon work better than a lower dose?
- How does alpha interferon affect the immune system? Researchers will compare six different treatment approaches to see which one works best.
Participants will:
- Have surgery to remove their melanoma
- Receive one of six different treatments after surgery:
- Radiation therapy (40 Gy)
- Low-dose interferon (3 million IU)
- Surgery alone (no additional treatment)
- High-dose interferon (9 million IU/m² IV)
- Low-dose interferon with chemotherapy (dacarbazine + cisplatin)
- Chemotherapy alone (dacarbazine + cisplatin)
- Have regular check-ups to see if the cancer returns
- Have blood tests to check immune system function Key finding: The study will determine which treatment approach provides the best chance of survival without cancer recurrence.
详细描述
Study Rationale Cutaneous melanoma has a clinically meaningful risk of recurrence after complete surgical resection, particularly in higher-risk disease. Interferon alfa has historically been investigated as adjuvant immunotherapy in melanoma; randomized trials and meta-analyses have shown modest improvements in relapse-related endpoints with clinically important toxicity, and no consistent evidence that higher-dose strategies provide greater benefit than lower-dose strategies.
This study compared multiple adjuvant approaches used in local practice, including differing interferon dose intensities and combinations with cytotoxic chemotherapy or radiotherapy, to explore their comparative associations with recurrence and survival outcomes.
Study Design and Setting This was a single-country, comparative interventional study conducted after definitive surgery for cutaneous melanoma. Participants were allocated to one of six post-operative management groups based on clinical factors and treatment availability (non-randomized, open-label assignment).
Interventions (post-operative groups)
After surgical resection, participants received one of the following:
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Outcomes Assessor)
盲法说明
This is an open-label study. Participants, care providers, and investigators are aware of the treatment assignments. However, the outcomes assessor performing the survival analysis and CD4/CD8 ratio measurements is blinded to treatment allocation to reduce bias in outcome assessment.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •• Histologically confirmed diagnosis of skin melanoma (stages I-IV according to TNM classification)
- •Underwent complete surgical resection of primary tumor with negative margins
- •Age 18 years or older
- •Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- •Life expectancy of at least 6 months
- •Adequate bone marrow function: absolute neutrophil count ≥ 1.5 × 10⁹/L, platelet count ≥ 100 × 10⁹/L, hemoglobin ≥ 90 g/L
- •Adequate hepatic function: bilirubin ≤ 1.5 × upper limit of normal (ULN), transaminases ≤ 2.5 × ULN
- •Adequate renal function: creatinine ≤ 1.5 × ULN or creatinine clearance ≥ 50 mL/min
- •Willing and able to provide written informed consent
- •Willing to comply with study procedures and follow-up schedule
排除标准
- •• Presence of distant metastases at the time of diagnosis (except for stage IV patients included per protocol)
- •Prior immunotherapy, chemotherapy, or radiotherapy for melanoma
- •History of other malignant neoplasms within the past 5 years (except non-melanoma skin cancer or carcinoma in situ of the cervix)
- •Severe or uncontrolled organ dysfunction (cardiac, hepatic, renal, pulmonary)
- •Active infection requiring systemic therapy
- •Known hypersensitivity to interferon-alpha or any study medications
- •Known hypersensitivity to dacarbazine, cisplatin, or any excipients
- •Pregnancy or breastfeeding
- •Psychiatric or cognitive impairment that would interfere with study participation
- •Participation in another interventional clinical trial within 30 days prior to enrollment
- •Any condition that, in the investigator's opinion, would compromise participant safety or interfere with study objectives
研究组 & 干预措施
Surgery + Low-Dose IFN-α + Polychemotherapy
Surgical resection followed by sequential immunochemotherapy. Phase 1: Low-dose interferon alfa 3 million IU intradermal daily to cumulative 30 million IU. Phase 2: 6 cycles of polychemotherapy (every 21 days): dacarbazine 1400 mg IV + cisplatin 50 mg IV. Indicated for locoregional melanoma (T3-4N0-1M0) with intermediate/high metastasis risk. n=47 patients.
干预措施: Skinscope Dermatoscopy (Diagnostic Test)
Surgery + Polychemotherapy Alone (Control)
Surgical resection followed by adjuvant polychemotherapy alone (control group for locoregional melanoma). Regimen: 6 cycles every 21 days of dacarbazine 1400 mg IV + cisplatin 50 mg IV. Indicated for locoregional melanoma (T3-4N0-1M0) with intermediate/high metastasis risk. n=43 patients.
干预措施: Immunological Monitoring (Diagnostic Test)
Surgery + Polychemotherapy Alone (Control)
Surgical resection followed by adjuvant polychemotherapy alone (control group for locoregional melanoma). Regimen: 6 cycles every 21 days of dacarbazine 1400 mg IV + cisplatin 50 mg IV. Indicated for locoregional melanoma (T3-4N0-1M0) with intermediate/high metastasis risk. n=43 patients.
干预措施: Skinscope Dermatoscopy (Diagnostic Test)
Surgery + Low-Dose IFN-α
Surgical resection followed by low-dose interferon alfa immunotherapy. Regimen: 3 million IU intradermal daily until cumulative dose 30 million IU, then maintenance therapy (3 million IU single dose) administered only when CD4/CD8 ratio drops below 1.3. Indicated for localized melanoma (T1-4N0M0) with low/intermediate metastasis risk. n=38 patients
干预措施: Surgical resection (Procedure)
Surgery + Low-Dose IFN-α
Surgical resection followed by low-dose interferon alfa immunotherapy. Regimen: 3 million IU intradermal daily until cumulative dose 30 million IU, then maintenance therapy (3 million IU single dose) administered only when CD4/CD8 ratio drops below 1.3. Indicated for localized melanoma (T1-4N0M0) with low/intermediate metastasis risk. n=38 patients
干预措施: Immunological Monitoring (Diagnostic Test)
Surgery + Low-Dose IFN-α
Surgical resection followed by low-dose interferon alfa immunotherapy. Regimen: 3 million IU intradermal daily until cumulative dose 30 million IU, then maintenance therapy (3 million IU single dose) administered only when CD4/CD8 ratio drops below 1.3. Indicated for localized melanoma (T1-4N0M0) with low/intermediate metastasis risk. n=38 patients
干预措施: Skinscope Dermatoscopy (Diagnostic Test)
Surgery + Radiotherapy
Surgical resection of primary melanoma with wide excision (4-5 cm margin on trunk, 3 cm on head/neck) followed by adjuvant radiotherapy. Radiation: external beam gamma therapy, 2 Gy daily fraction, total dose 40 Gy to primary site, 20 Gy to regional lymph node area. Indicated for localized melanoma (T1-2N0M0) with Clark invasion level I-II. n=49 patients.
干预措施: Surgical resection (Procedure)
Surgery + Radiotherapy
Surgical resection of primary melanoma with wide excision (4-5 cm margin on trunk, 3 cm on head/neck) followed by adjuvant radiotherapy. Radiation: external beam gamma therapy, 2 Gy daily fraction, total dose 40 Gy to primary site, 20 Gy to regional lymph node area. Indicated for localized melanoma (T1-2N0M0) with Clark invasion level I-II. n=49 patients.
干预措施: Adjuvant Radiotherapy (Radiation)
Surgery + Radiotherapy
Surgical resection of primary melanoma with wide excision (4-5 cm margin on trunk, 3 cm on head/neck) followed by adjuvant radiotherapy. Radiation: external beam gamma therapy, 2 Gy daily fraction, total dose 40 Gy to primary site, 20 Gy to regional lymph node area. Indicated for localized melanoma (T1-2N0M0) with Clark invasion level I-II. n=49 patients.
干预措施: Immunological Monitoring (Diagnostic Test)
Surgery + Radiotherapy
Surgical resection of primary melanoma with wide excision (4-5 cm margin on trunk, 3 cm on head/neck) followed by adjuvant radiotherapy. Radiation: external beam gamma therapy, 2 Gy daily fraction, total dose 40 Gy to primary site, 20 Gy to regional lymph node area. Indicated for localized melanoma (T1-2N0M0) with Clark invasion level I-II. n=49 patients.
干预措施: Skinscope Dermatoscopy (Diagnostic Test)
Surgery Alone (Control)
Surgical resection only, no adjuvant therapy. Wide excision of primary melanoma with margins 4-5 cm on trunk, 3 cm on head/neck. Regional lymphadenectomy performed if enlarged nodes present. Indicated for localized melanoma (T1-4N0M0) with low/intermediate metastasis risk as control group. n=64 patients.
干预措施: Surgical resection (Procedure)
Surgery Alone (Control)
Surgical resection only, no adjuvant therapy. Wide excision of primary melanoma with margins 4-5 cm on trunk, 3 cm on head/neck. Regional lymphadenectomy performed if enlarged nodes present. Indicated for localized melanoma (T1-4N0M0) with low/intermediate metastasis risk as control group. n=64 patients.
干预措施: Immunological Monitoring (Diagnostic Test)
Surgery Alone (Control)
Surgical resection only, no adjuvant therapy. Wide excision of primary melanoma with margins 4-5 cm on trunk, 3 cm on head/neck. Regional lymphadenectomy performed if enlarged nodes present. Indicated for localized melanoma (T1-4N0M0) with low/intermediate metastasis risk as control group. n=64 patients.
干预措施: Skinscope Dermatoscopy (Diagnostic Test)
Surgery + High-Dose IFN-α
Surgical resection followed by high-dose interferon alfa immunotherapy. Regimen: 9 million IU/m² intravenous every 2 days for a total of 4 doses. Indicated for locoregional melanoma (T3-4N0-1M0) with intermediate/high metastasis risk. Treatment discontinued in 29.6% of patients due to severe adverse events (hepatotoxicity, nephrotoxicity, cardiotoxicity, flu-like syndrome, leukopenia). n=37 patients.
干预措施: Immunological Monitoring (Diagnostic Test)
Surgery + High-Dose IFN-α
Surgical resection followed by high-dose interferon alfa immunotherapy. Regimen: 9 million IU/m² intravenous every 2 days for a total of 4 doses. Indicated for locoregional melanoma (T3-4N0-1M0) with intermediate/high metastasis risk. Treatment discontinued in 29.6% of patients due to severe adverse events (hepatotoxicity, nephrotoxicity, cardiotoxicity, flu-like syndrome, leukopenia). n=37 patients.
干预措施: Skinscope Dermatoscopy (Diagnostic Test)
Surgery + Low-Dose IFN-α + Polychemotherapy
Surgical resection followed by sequential immunochemotherapy. Phase 1: Low-dose interferon alfa 3 million IU intradermal daily to cumulative 30 million IU. Phase 2: 6 cycles of polychemotherapy (every 21 days): dacarbazine 1400 mg IV + cisplatin 50 mg IV. Indicated for locoregional melanoma (T3-4N0-1M0) with intermediate/high metastasis risk. n=47 patients.
干预措施: Surgical resection (Procedure)
Surgery + High-Dose IFN-α
Surgical resection followed by high-dose interferon alfa immunotherapy. Regimen: 9 million IU/m² intravenous every 2 days for a total of 4 doses. Indicated for locoregional melanoma (T3-4N0-1M0) with intermediate/high metastasis risk. Treatment discontinued in 29.6% of patients due to severe adverse events (hepatotoxicity, nephrotoxicity, cardiotoxicity, flu-like syndrome, leukopenia). n=37 patients.
干预措施: Surgical resection (Procedure)
Surgery + Low-Dose IFN-α + Polychemotherapy
Surgical resection followed by sequential immunochemotherapy. Phase 1: Low-dose interferon alfa 3 million IU intradermal daily to cumulative 30 million IU. Phase 2: 6 cycles of polychemotherapy (every 21 days): dacarbazine 1400 mg IV + cisplatin 50 mg IV. Indicated for locoregional melanoma (T3-4N0-1M0) with intermediate/high metastasis risk. n=47 patients.
干预措施: Immunological Monitoring (Diagnostic Test)
Surgery + Polychemotherapy Alone (Control)
Surgical resection followed by adjuvant polychemotherapy alone (control group for locoregional melanoma). Regimen: 6 cycles every 21 days of dacarbazine 1400 mg IV + cisplatin 50 mg IV. Indicated for locoregional melanoma (T3-4N0-1M0) with intermediate/high metastasis risk. n=43 patients.
干预措施: Surgical resection (Procedure)
结局指标
主要结局
Recurrence-free survival
时间窗: Up to 5 years following surgical resection
Time from surgical resection to first documented recurrence of melanoma (local, regional, or distant) or death from any cause, whichever occurs first. Assessed through clinical examination, imaging studies, and histopathological confirmation when applicable.
5-year overall survival
时间窗: 5 years following surgical resection
Proportion of participants alive at 5 years following surgical resection. Survival status assessed through clinical follow-up visits and medical records review.
Change in CD4/CD8 Ratio
时间窗: Baseline and at 6 months post-treatment
Change in the ratio of CD4-positive to CD8-positive T lymphocytes from baseline to post-treatment. Measured by flow cytometry using peripheral blood samples. Assesses immunologic response to interferon-alpha therapy.
次要结局
- Incidence of treatment-related adverse events(Through treatment completion, up to 12 months)
- Time to recurrence(Up to 5 years following surgical resection)
- Disease-free survival(Up to 5 years following surgical resection)