Fotemustine and Dacarbazine Versus Dacarbazine +/- Alpha Interferon in Advanced Malignant Melanoma

Study Overview
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Brief Summary
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This study evaluated two chemotherapy regimens with and without the addition of interferon in patients with advanced or recurrent melanoma.

Official Title
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Fotemustine and Dacarbazine Versus Dacarbazine +/- Alpha Interferon in Advanced Malignant Melanoma: Phase III Study

Conditions
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Malignant Melanoma, Recurrent Melanoma

Intervention / Treatment
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* Drug: Dacarbazine
* Drug: Fotemustine
* Drug: Interferon Alfa-2b


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed diagnosis of malignant melanoma in advanced stage or recurrent after surgery, and not amenable to further surgery or local therapy. Presence of measurable disease Age > or = 18 years and < or = 75 years Performance status (ECOG) 0 - 2 (Appendix 2) Life expectancy ³ 3 months Adequate bone marrow function (ANC ³ 2,000/mmc; PTL ³ 100,000/mmc; Hb ³ 10 gr/dl), normal liver and renal function (bilirubin < 1.25 x N, creatinine < 1.25 x N, SGOT, SGPT < 3 times upper normal limit of testing laboratory. Written, informed consent prior to study specific procedures, with the understanding that the patient has the right to withdraw from the study at any time, without prejudice. Prior surgery > 3 weeks from initiating . If palliative radiation is needed, in case of non target lesions, it must be given prior to initiating chemotherapy. If palliative radiation is required during the study the patient should be permanently discontinued from further treatment. Adequate contraceptive measures during study participation for sexually active patients of child bearing potential must implement. Exclusion Criteria: Previous or concurrent malignancies at other sites with the exception of surgically cured carcinoma in-site of the cervix and basal or squamous cell carcinoma of the skin. Prior chemo-immunotherapy ( previous adjuvant immunotherapy is allowed) Known HIV disease. Concurrent treatment with other experimental drugs. Concurrent chemotherapy, immunotherapy, hormonal therapy (excluding contraceptives and replacement steroids), radiation therapy Pregnant or lactating females Previous or concurrent malignancies at other sites with the exception of surgically cured carcinoma in-site of the cervix and basal or squamous cell carcinoma of the skin. Prior chemo-immunotherapy ( previous adjuvant immunotherapy is allowed) Known HIV disease. Concurrent treatment with other experimental drugs. Concurrent chemotherapy, immunotherapy, hormonal therapy (excluding contraceptives and replacement steroids), radiation therapy

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A1<br>combination chemotherapy without interferon | Drug: Dacarbazine<br>* 900 mg / m2 every 3 weeks<br>Drug: Fotemustine<br>* 100 mg / m2 every 3 weeks<br>|
| Experimental: A2<br>combination chemotherapy with interferon | Drug: Dacarbazine<br>* 900 mg / m2 every 3 weeks<br>Drug: Fotemustine<br>* 100 mg / m2 every 3 weeks<br>Drug: Interferon Alfa-2b<br>* 5 M units every 3 weeks<br>|
| Active Comparator: B1<br>single agent dacarbazine without interferon | Drug: Dacarbazine<br>* 900 mg / m2 every 3 weeks<br>|
| Experimental: B2<br>single agent dacarbazine plus interferon | Drug: Dacarbazine<br>* 900 mg / m2 every 3 weeks<br>Drug: Interferon Alfa-2b<br>* 5 M units every 3 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) | Overall Survival was defined as the time from the date of randomisation to the date of death from any cause or the date of last follow-up for living patients. OS curves were estimated with the Kaplan - Meier (K-M) method and treatments were compared with a two - sided log - rank test. | 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival (PFS) | Progression Free Survival (PFS) was defined as the time from the date of randomisation to the date of progression of disease or death from any cause, whichever occurred first, or date of last follow-up for patients without progression and alive at the end of the study. PFS curves were estimated with the Kaplan - Meier (K-M) method and treatments were compared with a two-sided log-rank test. | 12 months | 
| Overall Response Rate (ORR) | Overall Response Rate (ORR) included Complete Response (CR) and Partial Response (PR). Complete Response (CR) was defined as disappearance of all symptoms and signs of all measurable disease, lasting for at least four weeks, without appearance of new lesions. Partial Response (PR) was defined as a > 50% reduction in the sum of the products of the perpendicular diameters of all measurable lesions, lasting for at least four weeks, without appearance of new lesions or enlargement of existing lesions. | 18 weeks from start of therapy | 
| Treatment Related Toxicity | worst grade CTC toxicity, for each cycle and overall, will be reported for each treatment arm | at end of each 3 week cycle of therapy up to the discontinuation |