Adjuvant Therapy of Skin Melanoma With Alpha Interferon and Naderin

NCT07671495 | Completed Phase 2

• 2 other identifiers: 5EAFO Protocol 2012
• Study Type: interventional
• Target: 278
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Melanoma Stage I; Melanoma Stage III; Melanoma Stage II; Skin Melanoma

Keywords

Melanoma; Alpha Interferon; Immunotherapy; Adjuvant Therapy; CD4/CD8 Ratio; Recurrence-Free Survival; Overall Survival

Outcome Measures

Primary Outcomes (3)

• Recurrence-free survival

  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.

  Up to 5 years following surgical resection

• 5-year overall survival

  Proportion of participants alive at 5 years following surgical resection. Survival status assessed through clinical follow-up visits and medical records review.

  5 years following surgical resection

• Change in CD4/CD8 Ratio

  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.

  Baseline and at 6 months post-treatment

Secondary Outcomes (3)

• 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

Study Arms (6)

Surgery + Radiotherapy

EXPERIMENTAL

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.

Procedure: Surgical resection; Radiation: Adjuvant Radiotherapy; Diagnostic Test: Immunological Monitoring; Diagnostic Test: Skinscope Dermatoscopy

Surgery + Low-Dose IFN-α

EXPERIMENTAL

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

Procedure: Surgical resection; Biological: interferon alfa; Diagnostic Test: Immunological Monitoring; Diagnostic Test: Skinscope Dermatoscopy

Surgery Alone (Control)

ACTIVE COMPARATOR

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.

Procedure: Surgical resection; Diagnostic Test: Immunological Monitoring; Diagnostic Test: Skinscope Dermatoscopy

Surgery + High-Dose IFN-α

EXPERIMENTAL

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.

Procedure: Surgical resection; Biological: interferon alfa; Diagnostic Test: Immunological Monitoring; Diagnostic Test: Skinscope Dermatoscopy

Surgery + Low-Dose IFN-α + Polychemotherapy

EXPERIMENTAL

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.

Procedure: Surgical resection; Biological: interferon alfa; Drug: Dacarbazine (DTIC); Drug: Cisplatin; Diagnostic Test: Immunological Monitoring; Diagnostic Test: Skinscope Dermatoscopy

Surgery + Polychemotherapy Alone (Control)

ACTIVE COMPARATOR

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.

Procedure: Surgical resection; Drug: Dacarbazine (DTIC); Drug: Cisplatin; Diagnostic Test: Immunological Monitoring; Diagnostic Test: Skinscope Dermatoscopy

Interventions

Surgical resection PROCEDURE

Wide excision of primary skin melanoma under general intravenous anesthesia. Incision margin: 4-5 cm from visible tumor edge on trunk, 3 cm on head and neck, excised as a single block with subcutaneous fat and superficial fascia. For lower extremity melanoma in 7 patients, wide excision performed without skin closure (open wound management). Regional lymphadenectomy (Duke's operation for inguinal area or axillary lymphadenectomy) performed if enlarged regional lymph nodes present or for Clark invasion level III-IV

Also known as: Wide excision, melanoma surgery

Surgery + High-Dose IFN-α; Surgery + Low-Dose IFN-α; Surgery + Low-Dose IFN-α + Polychemotherapy; Surgery + Polychemotherapy Alone (Control); Surgery + Radiotherapy; Surgery Alone (Control)

Adjuvant Radiotherapy RADIATION

External beam gamma radiotherapy delivered to primary melanoma site and regional lymph node area. Regimen: 2 Gray (Gy) per fraction daily. Total dose: 40 Gy to primary tumor site, 20 Gy to regional lymph node area. Indicated only for localized melanoma with Clark invasion level I-II (T1-2N0M0). Not recommended for deeper invasion (T3-4N0M0) as it may accelerate disease progression

Also known as: External beam radiotherapy, gamma therapy

Surgery + Radiotherapy

interferon alfa BIOLOGICAL

Recombinant interferon alfa (IFN-α) immunotherapy administered in two dosing regimens. Low-dose regimen: 3 million IU intradermal daily until cumulative 30 million IU, then maintenance 3 million IU single dose only when CD4/CD8 ratio \<1.3. High-dose regimen: 9 million IU/m² intravenous every 2 days for 4 total doses. High-dose regimen associated with severe adverse events (fever 39-40°C, headache, nausea, cardiotoxicity, hepatotoxicity, nephrotoxicity, leukopenia) leading to treatment discontinuation in 29.6% of patients.

Also known as: IFN-α, recombinant interferon alpha

Surgery + High-Dose IFN-α; Surgery + Low-Dose IFN-α; Surgery + Low-Dose IFN-α + Polychemotherapy

Dacarbazine (DTIC) DRUG

Alkylating agent chemotherapy. Administered intravenously at 1400 mg per cycle. Used in combination with cisplatin for adjuvant polychemotherapy. Cycle repeats every 21 days for total of 6 cycles. Common adverse effects: nausea, vomiting, stomatitis, alopecia, short-term diarrhea.

Also known as: DTIC, imidazole carboxamide

Surgery + Low-Dose IFN-α + Polychemotherapy; Surgery + Polychemotherapy Alone (Control)

Cisplatin DRUG

Platinum-based chemotherapy agent. Administered intravenously at 50 mg per cycle. Used in combination with dacarbazine for adjuvant polychemotherapy. Cycle repeats every 21 days for total of 6 cycles. Adverse effects: nausea, vomiting, nephrotoxicity (managed with hydration), ototoxicity

Also known as: CDDP, platinol

Surgery + Low-Dose IFN-α + Polychemotherapy; Surgery + Polychemotherapy Alone (Control)

Immunological Monitoring DIAGNOSTIC_TEST

Monitoring of cellular immunity parameters including CD3, CD4, CD8, and CD4/CD8 ratio (immune regulatory index) using monoclonal antibodies. Performed at baseline pre-surgery, then at 1 month post-surgery, every 2 months for first year, and every 3 months for subsequent 5 years. CD4/CD8 ratio \<1.3 indicates immunosuppression requiring intervention. Ratio decline over 3-6 months predicts disease recurrence in 98.2% of cases.

Also known as: CD4/CD8 ratio, immune regulatory index, flow cytometry

Surgery + High-Dose IFN-α; Surgery + Low-Dose IFN-α; Surgery + Low-Dose IFN-α + Polychemotherapy; Surgery + Polychemotherapy Alone (Control); Surgery + Radiotherapy; Surgery Alone (Control)

Skinscope Dermatoscopy DIAGNOSTIC_TEST

Non-invasive dermatoscopy device (Menard, Japan) for detecting subclinical intradermal satellite metastases in melanoma patients. Provides 40-80x magnification with surface and deep imaging modes. Enables photo/video capture and analysis. Sensitivity: 75.0±4.1% for detecting intradermal metastases vs. 26.0±3.4% with visual examination alone. Helps determine appropriate surgical margins. Priority certificate No.2009/1105.1 dated 04.09.2009.

Also known as: Menard Skinscope, video dermatoscopy

Surgery + High-Dose IFN-α; Surgery + Low-Dose IFN-α; Surgery + Low-Dose IFN-α + Polychemotherapy; Surgery + Polychemotherapy Alone (Control); Surgery + Radiotherapy; Surgery Alone (Control)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• MIPO Clinic: lead
• Asfendiyarov Kazakh National Medical University: collaborator
• Kazakh Research Institute of Oncology & Radiology: collaborator

MeSH Terms

Conditions

Melanoma

Interventions

Radiotherapy, Adjuvant; Interferon-alpha; Dacarbazine; Cisplatin; Monitoring, Immunologic; CD4-CD8 Ratio; Flow Cytometry

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Combined Modality Therapy; Therapeutics; Radiotherapy; Interferon Type I; Interferons; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Immunologic Tests; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Monitoring, Physiologic; Investigative Techniques; Immunologic Techniques; CD4 Lymphocyte Count; Lymphocyte Count; Leukocyte Count; Blood Cell Count; Cell Count; Cytological Techniques; Hematologic Tests; Cell Physiological Phenomena; Blood Physiological Phenomena; Circulatory and Respiratory Physiological Phenomena; Immune System Phenomena; Cell Separation; Cytophotometry; Fluorometry; Luminescent Measurements; Photometry; Chemistry Techniques, Analytical

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: 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.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Six parallel treatment groups based on TNM stage and risk category. Groups I-III (localized melanoma, n=151): surgery+radiotherapy (49), surgery+low-dose IFN-α (38), surgery alone (64). Groups IV-VI (locoregional melanoma, n=127): surgery+high-dose IFN-α (37), surgery+low-dose IFN-α+polychemotherapy (47), surgery+polychemotherapy alone (43). Non-randomized allocation.

Study Record Dates

• First Submitted: June 22, 2026
• First Posted: June 26, 2026
• Study Start: January 1, 2014
• Primary Completion: December 1, 2017
• Study Completion: December 1, 2018
• Last Updated: June 30, 2026

Record last verified: 2026-06