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Melanoma Stage IPhase 2ATSMAINNCT07671495

Adjuvant Therapy of Skin Melanoma With Alpha Interferon and Naderin

A Phase 2 study testing Surgical resection, Adjuvant Radiotherapy and interferon alfa in people with Melanoma Stage I and Melanoma Stage III, run by MIPO Clinic.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Surgical resection, Adjuvant Radiotherapy and interferon alfa
Could I receive a placebo?
No, everyone receives an active treatment
How many people
278 participants
Where
No sites listed yet
Study dates
Jan 2014to Dec 2018
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • • 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
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  • 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

Who cannot join

  • • 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
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  • 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

About this study

Official title: Protocol of Clinical Trial of EAFO 2012: Adjuvant Therapy of Skin Melanoma With Use of Alpha Interferon and Naderin

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:

Read more
  • 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.
Read the detailed description

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:

Adjuvant radiotherapy to the surgical bed: total dose 40 Gy.

Low-dose interferon alfa: 3 million IU subcutaneously on a scheduled regimen.

Observation / surgery alone (no adjuvant therapy).

Higher-dose interferon alfa: 9 million IU/m² intravenously on a scheduled regimen.

Low-dose interferon alfa + polychemotherapy: dacarbazine + cisplatin.

Polychemotherapy alone: dacarbazine + cisplatin. (Administration schedules, cycle lengths, and duration should be specified in the protocol or an accessible supporting document, consistent with protocol reporting standards.)

Assessments and Follow-up

Participants underwent baseline clinical evaluation after surgery and were followed at prespecified intervals for:

Disease status/recurrence surveillance (clinical assessments and imaging per local standard schedule).

Safety monitoring including treatment-emergent adverse events.

Immune monitoring via peripheral blood sampling with lymphocyte subset evaluation (including CD4/CD8 ratio) at baseline and predefined follow-up timepoints.

Outcomes (high-level; avoid duplicating Outcome Measures section) The study evaluated time-to-event and proportion-based clinical outcomes (recurrence and survival endpoints), safety/tolerability of each adjuvant approach, and longitudinal changes in immune markers.

Statistical Considerations (high-level) Time-to-event outcomes were planned for analysis using Kaplan-Meier methods with between-group comparisons using log-rank testing. Immune marker changes were planned for within- and between-group comparisons using parametric or nonparametric methods depending on distributional assumptions. A two-sided significance threshold of p < 0.05 was prespecified.

Limitations (protocol-relevant, non-results) Because treatment assignment was non-randomized, comparative estimates between groups are vulnerable to confounding by indication and selection bias. Interpretation of between-group differences therefore requires caution and may require adjustment methods (e.g., multivariable models/propensity approaches) if covariates were collected and sample size permits.

Being tested
Surgical resection, Adjuvant Radiotherapy, interferon alfa, Dacarbazine (DTIC), Cisplatin
Keywords
Melanoma, Alpha Interferon, Immunotherapy, Adjuvant Therapy, CD4/CD8 Ratio, Recurrence-Free Survival, Overall Survival
Medical subject headings
Melanoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Surgical resectionProcedure or surgery

    Also called Wide excision, melanoma surgery

    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

  • Adjuvant RadiotherapyRadiation

    Also called External beam radiotherapy, gamma therapy

    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

  • interferon alfaBiological

    Also called IFN-α, recombinant interferon alpha

    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.

  • Dacarbazine (DTIC)Drug

    Also called DTIC, imidazole carboxamide

    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.

  • CisplatinDrug

    Also called CDDP, platinol

    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

  • Immunological MonitoringDiagnostic test

    Also called CD4/CD8 ratio, immune regulatory index, flow cytometry

    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.

  • Skinscope DermatoscopyDiagnostic test

    Also called Menard Skinscope, video 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.

Study groups in NCT07671495
Study groupRoleWhat they receive
Surgery + RadiotherapyExperimentalSurgical 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.
Receives: Procedure: Surgical resection; Radiation: Adjuvant Radiotherapy; Diagnostic Test: Immunological Monitoring; Diagnostic Test: Skinscope Dermatoscopy
Surgery + Low-Dose IFN-αExperimentalSurgical 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
Receives: Procedure: Surgical resection; Biological: interferon alfa; Diagnostic Test: Immunological Monitoring; Diagnostic Test: Skinscope Dermatoscopy
Surgery Alone (Control)Active comparatorSurgical 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.
Receives: Procedure: Surgical resection; Diagnostic Test: Immunological Monitoring; Diagnostic Test: Skinscope Dermatoscopy
Surgery + High-Dose IFN-αExperimentalSurgical 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.
Receives: Procedure: Surgical resection; Biological: interferon alfa; Diagnostic Test: Immunological Monitoring; Diagnostic Test: Skinscope Dermatoscopy
Surgery + Low-Dose IFN-α + PolychemotherapyExperimentalSurgical 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.
Receives: Procedure: Surgical resection; Biological: interferon alfa; Drug: Dacarbazine (DTIC); Drug: Cisplatin; Diagnostic Test: Immunological Monitoring; Diagnostic Test: Skinscope Dermatoscopy
Surgery + Polychemotherapy Alone (Control)Active comparatorSurgical 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.
Receives: Procedure: Surgical resection; Drug: Dacarbazine (DTIC); Drug: Cisplatin; Diagnostic Test: Immunological Monitoring; Diagnostic Test: Skinscope Dermatoscopy

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Up to 5 years following surgical resection

  2. 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.

    Measured: 5 years following surgical resection

  3. 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.

    Measured: Baseline and at 6 months post-treatment

Secondary outcomes (3)

  1. Incidence of treatment-related adverse events

    Proportion of participants experiencing treatment-related adverse events, including severity grading according to Common Terminology Criteria for Adverse Events (CTCAE). Particular focus on toxicity leading to treatment discontinuation.

    Measured: Through treatment completion, up to 12 months

  2. Time to recurrence

    Time from surgical resection to first documented recurrence of melanoma, measured in months. Participants without recurrence are censored at the date of last follow-up.

    Measured: Up to 5 years following surgical resection

  3. Disease-free survival

    Time from surgical resection to first recurrence, second primary melanoma, or death from any cause, whichever occurs first.

    Measured: Up to 5 years following surgical resection

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted26 Jun 2026
  2. Study startJan 2014
  3. Primary completionDec 2017
  4. Study completionDec 2018

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Model description
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.
Masking
Single blind
Who is masked
Outcomes assessor
Enrolment
278 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07671495
Sponsor's protocol ID
5
Other IDs
EAFO Protocol 2012
Acronym
ATSMAIN
Status last verified
Jun 2026
First submitted
22 Jun 2026
Last updated
30 Jun 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Surgical resection, Adjuvant Radiotherapy and interferon alfa in people with Melanoma Stage I and Melanoma Stage III, run by MIPO Clinic.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 30 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Recurrence-free survival (time frame: Up to 5 years following surgical resection). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT07671495.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Jun 2026.

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