Thymosin Alpha 1, Interferon Alpha, or Both, in Combination With Dacarbazine in Patients With Malignant Melanoma

A Phase II, Multicentre, Open, Randomised, Dose Ranging Study to Investigate the Efficacy of Combination Therapy Containing Dacarbazine (DTIC) Plus Low Dose Interferon Alpha (aIFN) Plus Thymosin a1 Versus Both DTIC Plus Thymosin a1 and DTIC Plus aIFN in Patients With Advanced -Stage Metastatic Malignant Melanoma

The purpose of the study is to test safety and efficacy of different doses of thymosin alpha 1 (1.6 mg, 3.2 mg, and 6.4 mg) in combination with dacarbazine and with or without Interferon alpha in treating patients affected by stage IV melanoma.

Primary end-point is Tumor Response evaluated according to Response Evaluation Criteria In Solid Tumors (RECIST). Secondary end-points are Overall Survival and Progression Free Survival.

Ninety-five patients are allocated to each arm to test the hypothesis that P0 <= 0.05 vs the alternative hypothesis that P1 >= 0.15 (alpha = 5%, within-group statistical analysis beta = 95%).

Study Overview

• Status: Completed
• Conditions: Malignant Melanoma
• Intervention / Treatment: Biological: Dacarbazine + Interferon alpha + Thymosin-alpha-1 1.6 mg; Biological: Dacarbazine + Interferon alpha + Thymosin-alpha-1 3.2 mg; Biological: Dacarbazine + Interferon alpha + Thymosin-alpha-1 6.4 mg; Biological: Dacarbazine + Thymosin-alpha-1 3.2 mg; Drug: Dacarbazine + Interferon alpha

• Study Type: Interventional
• Enrollment (Actual): 488
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • La Tronche, France, 38043
    • CHU de Grenoble Hopital Albert Michallon Service de Dermatologie
  • Limoges, France, 87042
    • CHU de Limoges Hopital Dupuytren Service de Dermatologie
  • Montpellier, France, 34295
    • Hopital Saint-Eloi Service de Dermatologie
  • Rennes, France, 35042
    • Centre Eugene Marquis Departement d'Oncologie Medicale
  • Toulouse, France, 31059
    • Hopital Purpan Service de Dermatologie
• Germany
  • Aachen, Germany, 52074
    • Klinik fur Dermatologie und Allergologie der RWTH Aachen
  • Berlin, Germany, 10117
    • Klinik fur Dermatologie, Venerologie und Allergologie des Campus Charitè Mitte
  • Buxtehude, Germany, 21614
    • Elbeklinikec Buxtehude Dermatologische Zentrum Abteilung fur Dermato-Onkologie
  • Frankfurt, Germany, 60590
    • Zentrum fur Dermatologie und Veneralogie Klinik der Johann-Wolfgang-Goethe-Universitat
  • Hannover, Germany, D-30449
    • Klinikum Hannover, Hautklinik Linden
  • Kiel, Germany, 24105
    • Universitatsklinikum Schlewig-Holstein Klinik fur Dermatologie, Veneralogie und Allergologie Universitats-Hautklinik Kiel
  • Magdeburg, Germany, 39120
    • Universitatsklinik fur Dermatologie und Venerologie Otto-von-Guericke-Universitat Magdeburg
  • Tubingen, Germany, 72076
    • Dermatologische Klinik der Universitat Tubingen
• Hungary
  • Budapest, Hungary, H-1085
    • Orszagos Bor-es Nemikortani Intezet
  • Budapest, Hungary, H-1122
    • Orszagos Onkologiai Intezet Borgyogyaszat
  • Gyor, Hungary, H-9024
    • Petz Aladar Megyei Korhaz, Borgyogyaszat
  • Miskolc, Hungary, H-3501
    • Miskolc Megyei Korhaz Borgyogyaszat
  • Pecs, Hungary, H-7600
    • Pecsi Egyetem Borgyogyaszati Klinika
  • Szeged, Hungary, H-6701
    • Szegedi Egyetem Borgyogyaszati Klinika
• Italy
  • Agrigento, Italy
    • ASL 1 Servizio di Oncologia
  • Caltanissetta, Italy, 93100
    • Azienda Ospedaliera S. Elia, UO di Oncologia
  • Catania, Italy, 95126
    • Azienda Ospedaliera Garibaldi, UO Oncologia Medica
  • Chieti, Italy, 66100
    • Università "G. D'Annunzio" Facoltà di Medicina e Chirurgia, Clinica Dermatologica
  • Enna, Italy, 94100
    • Azienda Ospedaliera Umberto I° UO Servizio di Oncologia e Chemioterapia
  • Firenze, Italy, 50121
    • Università di Firenze Dipartimento di Scienze Dermatologiche
  • Forli, Italy, 47100
    • Ospedale Pierantoni, Divisione Oncologia Medica
  • Genova, Italy, 16132
    • Istituto NazionaleRicerca sul Cancro, Dipartimento di Oncologia Medica 1
  • Milano, Italy, 20141
    • Istituto Europeo di Oncologia, Divisione di Chirurgia Generale
  • Milano, Italy, 20159
    • Casa di Cura San Pio X, UO Oncologia Medica
  • Ragusa, Italy, 97100
    • Ospedale Civile, UO di Oncologia
  • Reggio Calabria, Italy, 89100
    • Azienda Ospedaliera Bianchi-Melacrino-Morelli, Oncologia Medica
  • Roma, Italy, 00133
    • Università di Roma "Tor Vergata" Oncologia Complementare, Dipartimento di Chirurgia
  • Roma, Italy, 00144
    • IFO Polo Oncologico Ist. Regina Elena, Divisione di Oncologia Medica A
  • Roma, Italy, 00157
    • Ospedale Sandro Pertini, Oncologia Medica
  • Roma, Italy, 00161
    • Università "La Sapienza" Dipartimento di Malattie Cutanee-Veneree e Chirurgia Plastica Ricostruttiva
  • Roma, Italy, 00167
    • Istituto Dermopatico dell'Immacolata, Dipartimento di Immunodermatologia
  • Siena, Italy, 53100
    • Policlinico "Le Scotte" Dipartimento di Medicina Clinica, Scienze Immunologiche Applicate, Divisione di Dermatologia
  • Siena, Italy, 53100
    • U.O. Complessa, Immunoterapia Oncologica, Policlinico "Le Scotte"
  • Siracusa, Italy, 96100
    • Ospedale Umberto I°, Divisione di Oncologia Medica
  • Viterbo, Italy, 01100
    • Ospedale Bel Colle UO di Oncologia
  • Frosinone
    • Sora, Frosinone, Italy, 03039
      • Ospedale SS Trinità Oncologia
  • Messina
    • Taormina, Messina, Italy, 98039
      • Ospedale San Vincenzo U.O. Oncologia Medica
  • Roma
    • Albano Laziale, Roma, Italy, 00041
      • UO Complessa Aziendale Nettuno/Albano/Frascati Day-Hospital di Oncologia Ospedale S. Giuseppe
  • Venezia
    • Noale, Venezia, Italy, 30033
      • Ospedale PF Calvi Dipartimento di Oncologia
• Poland
  • Gdansk, Poland, 80-211
    • Katedra i Klinika Onkologii i Radioterapii Akademia Medyczna
  • Krakow, Poland, 31-115
    • Instytut Onkologii im. Marii Sklodowskiej-Curie, Oddzial w Krakowie, Klinika Chemioterapii
  • Lodz, Poland, 93-509
    • Wojewodzki Szpital Specjalistyczny im. M. Kopernika, Klinika Chemioterapii Oncologicznej
  • Lublin, Poland, 20-081
    • Samodzielny Publiczny Szpital Kliniczny nr 1, Klinika Chirurgii Onkologicznej
  • Poznan, Poland, 61-868
    • Wielkopolskie Centrum Onkologii, Zaklad Immunologii Nowotworow Katedry Onkologii AM
  • Szczecin, Poland, 71-730
    • Oddzial Chemioterapii
  • Warszawa, Poland
    • Klinika Onkologii Centralnego Szpitala WAM
  • Wroclaw, Poland, 53-439
    • Dolnoslakie Centrum Transplantacji Komorkowych z Krajowym Bankiem Dawcow Szpiku
• Portugal
  • Lisboa, Portugal, 1099-023
    • Instituto Portugues de Oncologia de Francisco Gentil, Centro Regional de Oncologia de Lisboa S.A., Servicio de Medicina Oncologica 1, Pavilhao C
  • Porto, Portugal, 4200
    • Instituto Portugues de Oncologia de Francisco Gentil, Centro Regional de Oncologia do Porto S.A., Servicio de Medicina Oncologica, Piso 3
• Spain
  • Barcelona, Spain, 08036
    • Hosp. Clinic i Provincial Servicio de Oncologia
  • Jaen, Spain, 23007
    • Hosp. Universitario de Jaen Servicio de Oncologia
  • Madrid, Spain, 28040
    • Hosp. Clinico San Carlos Servicio de Oncologia, Pabellon B, Ala Sur-Sotano
  • Malaga, Spain, 29010
    • Hosp. Virgen de la Victoria de Malaga Servicio de Oncologia 1a planta Campus Universitario de Teatinos
  • Sevilla, Spain, 41013
    • Hosp. Virgen del Rocio Servicio de Oncologia, Planta Baja - Centro de Diagnostico
  • Valencia, Spain, 46009
    • Instituto Valenciano Oncologico
  • Valencia, Spain, 46014
    • Hospital General Universitario de Valencia Unidad de Oncologia Medica
  • Barcelona
    • L'hospitalet de Llobregat, Barcelona, Spain, 08907
      • Instituto Catalan Oncologico, Servicio de Oncologia
  • Santa Cruz de Tenerife
    • La Laguna, Santa Cruz de Tenerife, Spain, 38320
      • Hosp. Univ. de Canarias Servicio de Oncologia Medica
• Switzerland
  • Aarau, Switzerland, CH-5001
    • Zentrum fur Onkologie Hematologie und Transfusionsmedizin am Kantonsspital Aarau

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 71 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Have read and signed the informed consent form
• 18 years <=Age<= 75 years
• Adequate contraception practice (fertile female patient)
• Confirmed diagnosis of metastatic melanoma (stage IV) with unresectable metastases and >= 1 measurable lesion
• Adequate renal function as demonstrated by serum creatinine level < 1.5 mg/deciliter (dl)
• Absolute Neutrophil Count (ANC) >= 1.5 x 10000000000/L ; platelets >= 100 x 10000000000/Liter (L)
• Good performance status: PS <= 1 (ZUBROD-ECOG-WHO scale)
• At least 12 week life expectancy

Exclusion Criteria:

• Clinical diagnosis of autoimmune disease
• Transplant recipient
• Pregnancy documented by a urine pregnancy test or lactation
• Previous treatment with thymosin alpha 1
• Previous treatment with chemotherapy
• Presence of Central Nervous System (CNS) metastases
• Concomitant or prior history of malignancy other than melanoma
• Participation in another investigational trial within 30 days of study entry
• Active infectious process that is not of self-limiting nature

Study Plan

How is the study designed?

Design Details

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

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dacarbazine + Interferon alpha + thymosin-alpha-1 1.6 mg; Dacarbazine 800 mg/m2 IV on day 1; Interferon alpha 3MIU SC on day 11 and 18; Thymosin-alpha-1 1.6 mg SC from day 8 to 11 and from day 15 to 18 of each 28 day cycle up to 6 cycles or until progression or unacceptable toxicity develops.	Biological: Dacarbazine + Interferon alpha + Thymosin-alpha-1 1.6 mg; Dacarbazine 800 mg/m2 IV on day 1;Interferon alpha 3MIU SC on day 11 and 18; Thymosin-alpha-1 1.6 mg SC from day 8 to 11 and from day 15 to 18 of each 28 day cycle up to 6 cycles or until progression or unacceptable toxicity develops.; Other Names: Deticene; Zadaxin; Roferon; Thymalfasin; ST1472
Experimental: Dacarbazine + Interferon alpha + Thymosin-alpha-1 3.2 mg; Dacarbazine 800 mg/m2 IV on day 1; Interferon alpha 3MIU SC on day 11 and 18; Thymosin-alpha-1 3.2 mg SC from day 8 to 11 and from day 15 to 18 of each 28 day cycle up to 6 cycles or until progression or unacceptable toxicity develops.	Biological: Dacarbazine + Interferon alpha + Thymosin-alpha-1 3.2 mg; Dacarbazine 800 mg/m2 IV on day 1; Interferon alpha 3MIU SC on day 11 and 18; Thymosin-alpha-1 3.2 mg SC from day 8 to 11 and from day 15 to 18 of each 28 day cycle up to 6 cycles or until progression or unacceptable toxicity develops.; Other Names: Deticene; Zadaxin; Roferon; Thymalfasin; ST1472
Experimental: Dacarbazine + Interferon alpha + Thymosin-alpha-1 6.4 mg; Dacarbazine 800 mg/m2 IV on day 1; Interferon alpha 3MIU SC on day 11 and 18; Thymosin-alpha-1 6.4 mg SC from day 8 to 11 and from day 15 to 18 of each 28 day cycle up to 6 cycles or until progression or unacceptable toxicity develops.	Biological: Dacarbazine + Interferon alpha + Thymosin-alpha-1 6.4 mg; Dacarbazine 800 mg/m2 IV on day 1; Interferon alpha 3MIU SC on day 11 and 18 Thymosin-alpha-1 6.4 mg SC from day 8 to 11 and from day 15 to 18 of each 28 day cycle up to 6 cycles or until progression or unacceptable toxicity develops.; Other Names: Deticene; Zadaxin; Roferon; Thymalfasin; ST1472
Experimental: Dacarbazine + Thymosin-alpha-1 3.2 mg; Dacarbazine 800 mg/m2 IV on day 1; Thymosin-alpha-1 3.2 mg SC from day 8 to 11 and from day 15 to 18 of each 28 day cycle up to 6 cycles or until progression or unacceptable toxicity develops.	Biological: Dacarbazine + Thymosin-alpha-1 3.2 mg; Dacarbazine 800 mg/m2 IV on day 1; Thymosin-alpha-1 3.2 mg SC from day 8 to 11 and from day 15 to 18 of each 28 day cycle up to 6 cycles or until progression or unacceptable toxicity develops.; Other Names: Deticene; Zadaxin; Thymalfasin; ST1472
Active Comparator: Dacarbazine + Interferon alpha; Dacarbazine 800 mg/m2 IV on day 1; Interferon alpha 3MIU SC on day 11 and 18 of each 28 day cycle up to 6 cycles or until progression or unacceptable toxicity develops.	Drug: Dacarbazine + Interferon alpha; Dacarbazine 800 mg/m2 IV on day 1; Interferon alpha 3MIU SC on day 11 and 18 of each 28 day cycle up to 6 cycles or until progression or unacceptable toxicity develops.; Other Names: Deticene; Roferon

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Tumor Response	Tumor response is measured according to Response Evaluation Criteria In Solid Tumors (RECIST) computing number of Complete Response plus Partial Response	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival	The survival time for each patient is defined as the time between randomization and death. Patients lost to follow-up or still alive at the date of last evaluation have been censored.	2 years
Progression Free Survival	Progression Free Survival is defined as the time from the randomization to progression or death	2 years

Collaborators and Investigators

• Sponsor: sigma-tau i.f.r. S.p.A.
• Investigators: Principal Investigator: Virginia Ferraresi, MD, IFO Polo Oncologico Ist. Regina Elena, Divisione Oncologia Medica A - ROMA; Study Director: Roberto Camerini, MD, Sigma-tau SPA

Study record dates

Study Major Dates

• Study Start: July 1, 2002
• Primary Completion (Actual): September 1, 2007
• Study Completion (Actual): September 1, 2007

Study Registration Dates

• First Submitted: February 26, 2009
• First Submitted That Met QC Criteria: April 7, 2009
• First Posted (Estimate): June 2, 2009

Study Record Updates

• Last Update Posted (Estimate): July 9, 2009
• Last Update Submitted That Met QC Criteria: July 1, 2009
• Last Verified: July 1, 2009

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; Adjuvants, Immunologic; Interferons; Interferon-alpha; Interferon alpha-2; Dacarbazine; Thymalfasin
• Other Study ID Numbers: ST1472DM01012