Fotemustine and Dacarbazine Versus Dacarbazine +/- Alpha Interferon in Advanced Malignant Melanoma (SICOG 0109)

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

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

Study Overview

• Status: Completed
• Conditions: Recurrent Melanoma; Malignant Melanoma
• Intervention / Treatment: Drug: Dacarbazine; Drug: Fotemustine; Drug: Interferon Alfa-2b

• Study Type: Interventional
• Enrollment (Actual): 269
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: National Cancer Institute, Naples
• Investigators: Principal Investigator: Paolo A Ascierto, M.D., Ph.D., NCI Naples; Principal Investigator: Antonio Daponte, M.D., NCI Naples; Principal Investigator: Simona Signoriello, M.D., University of Campania "Luigi Vanvitelli"

Publications and helpful links

General Publications

• Daponte A, Signoriello S, Maiorino L, Massidda B, Simeone E, Grimaldi AM, Caraco C, Palmieri G, Cossu A, Botti G, Petrillo A, Lastoria S, Cavalcanti E, Aprea P, Mozzillo N, Gallo C, Comella G, Ascierto PA; Southern Italy Cooperative Oncology Group (SICOG). Phase III randomized study of fotemustine and dacarbazine versus dacarbazine with or without interferon-alpha in advanced malignant melanoma. J Transl Med. 2013 Feb 13;11:38. doi: 10.1186/1479-5876-11-38.

Study record dates

Study Major Dates

• Study Start: April 1, 2002
• Primary Completion (Actual): February 1, 2011
• Study Completion (Actual): February 1, 2011

Study Registration Dates

• First Submitted: May 13, 2011
• First Submitted That Met QC Criteria: May 24, 2011
• First Posted (Estimate): May 25, 2011

Study Record Updates

• Last Update Posted (Actual): April 11, 2023
• Last Update Submitted That Met QC Criteria: March 15, 2023
• Last Verified: September 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Melanoma; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Antineoplastic Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Interferons; Interferon-alpha; Interferon alpha-2; Dacarbazine; Fotemustine
• Other Study ID Numbers: SICOG 0109