Melanoma
Conditions
Keywords
interferon-alpha
Brief summary
The aim of this observational study is to document the efficacy and tolerability of high-dose interferon therapy in adult participants with malignant melanoma at high risk of relapse and to compare them with the survival times and relapse rates in previous studies (historical control).
Detailed description
Observational study to evaluate the tolerability and efficacy (vs historical controls) of a high-dose therapy scheme with interferon-α-2b (IntronA®): Adjuvant treatment with interferon-α-2 has been demonstrated in a number of studies to have an antiproliferative effect on malignant melanoma. In these cases a response rate of up to 20% could be achieved with a dose of 10 million IU or more 3x/week or daily. Kirkwood et al. showed in a study carried out in ECOG (the Eastern Cooperative Oncology Group, study no. 1684) that there was a clear and significant survival advantage versus the observation group with the following dose: 20 mio IU/m² interferon-α-2b (IntronA®) 5x/week iv over the course of one month followed by 11 months with 10 mio IU/m² 3x/week sc.
Interventions
BIOLOGICALInterferon α-2b
20 mio IU/m² interferon-α-2b 5x/week intravenously (IV) over the course of 1 month, followed by 10 mio IU/m² interferon-α-2b 3x/week subcutaneously (SC) for 11 months.
Sponsors
Merck Sharp & Dohme LLC
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Male and female participants * Age 18-70 years * Malignant melanoma stage II or III (\>/= 1.5 mm tumor thickness, no distant metastases or Malignant melanoma with lymph node metastases or Lymph node metastases with unknown primary tumor * An excision border of at least 2 cm around the primary tumor * Therapy must start within 12 weeks after surgery of the tumor/of the lymph node metastases * ECOG status 0-1 (= Karnofsky Index \>/= 80) * Laboratory parameters * Hematocrit \>= 33% * Leukocytes \>= 3000/μl * Thrombocytes \>= 100000/μl * Alanine aminotransferase(ALT) \<= 2x normal values * Bilirubin \<= 2x normal values
Exclusion criteria
* Known allergy to one of the medications or any of its component parts * Refusal on the part of participants capable of childbearing to use a reliable contraceptive * Lactating mothers * Presence of distant metastases * Another primary tumor of different histological origin than corresponding to the indication (except when the relapse-free interval is \> 5 years, or the tumor is a cervical carcinoma in situ, a basal cell carcinoma or cutaneous squamous cell carcinoma) * Participants on corticosteroid treatment or treatment with an immunomodulating substance * Preexisting psychiatric illness, particularly serious depression * Prior adjuvant radio-, chemo-, or immuno-therapy * Treatment with an investigational drug within the prior 30 days * Participant history that includes cardiac arrhythmia, cardiac insufficiency requiring treatment, or anthracycline administration * Myocardial infarction within the prior year * An unstable medical condition (apart from the indication) that in the judgment of the investigating physician excludes the participants from the study * Psoriasis (a relative exclusion criterion, since interferon can aggravate psoriasis; decision to be based on risk/benefit analysis)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Disease Recurrence | Throughout 12 months of treatment and 24 months of follow-up | Number of participants with disease recurrence was being measured. |
| Relapse Free Survival Time | Throughout 12 months of treatment and 24 months of follow-up | Median time to recurrence according to Kaplan Maier evaluation |
Participant flow
Recruitment details
Male and female participants, with malignant melanoma Stage II or III (\>1.5 mm tumor thickness, no distant metastasis) or malignant melanoma with evidence of lymph node metastis or lymph node metastasis of malignant melanoma at unknown primary tumor, primary tumor has to be surgically resected within 2 months after first biopsy/excision.
Participants by arm
| Arm | Count |
|---|---|
| Adults With Malignant Melanoma at High Risk of Relapse Adults with malignant melanoma of the following stages:
* II and III (\>/= 1.5 mm Breslow thickness without distant metastases
* melanoma with lymph node metastases | 138 |
| Total | 138 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 27 |
| Overall Study | AE+discontinuation on participants wish | 1 |
| Overall Study | Death | 1 |
| Overall Study | Missing | 9 |
| Overall Study | Not Documented | 1 |
| Overall Study | Participant's Wish | 10 |
| Overall Study | Progressive Desease | 31 |
| Overall Study | Therapy according to protocol + AE | 2 |
Baseline characteristics
| Characteristic | Adults With Malignant Melanoma at High Risk of Relapse |
|---|---|
| Age, Continuous Female | 48.27 participants STANDARD_DEVIATION 12.49 |
| Age, Continuous Male | 49.15 participants STANDARD_DEVIATION 12.91 |
| Age, Continuous Total | 48.83 participants STANDARD_DEVIATION 12.72 |
| Sex: Female, Male Female | 50 Participants 12.49 |
| Sex: Female, Male Male | 88 Participants 12.91 |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 75 / 138 |
| serious Total, serious adverse events | 11 / 138 |
Outcome results
Primary
Number of Participants With Disease Recurrence
Number of participants with disease recurrence was being measured.
Time frame: Throughout 12 months of treatment and 24 months of follow-up
Population: 138 participants with malignant melanoma, 88 male participants and 50 female participants were evaluated.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Adults With Malignant Melanoma at High Risk of Relapse | Number of Participants With Disease Recurrence | 52 participants |
Primary
Relapse Free Survival Time
Median time to recurrence according to Kaplan Maier evaluation
Time frame: Throughout 12 months of treatment and 24 months of follow-up
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Adults With Malignant Melanoma at High Risk of Relapse | Relapse Free Survival Time | 54.1 months |