Adjuvant Therapy of Skin Melanoma With Alpha Interferon and Naderin

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

Interventions

PROCEDURE

Surgical resection

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

RADIATION

Adjuvant Radiotherapy

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

BIOLOGICAL

interferon alfa

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.

DRUG

Dacarbazine (DTIC)

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.

DRUG

Cisplatin

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

DIAGNOSTIC_TEST

Immunological Monitoring

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.

DIAGNOSTIC_TEST

Skinscope Dermatoscopy

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.

Sponsors & Collaborators

• Asfendiyarov Kazakh National Medical University

  collaborator OTHER

• Kazakh Research Institute of Oncology & Radiology

  collaborator OTHER

• MIPO Clinic

  lead OTHER

Study Design

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

SINGLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2014-01-31

Primary Completion

2017-12-31

Completion

2018-12-31