Trial of Dacarbazine With or Without Genasense in Advanced Melanoma

Melanoma Clinical Trial

— AGENDA  

Official title:

A Multicenter, Randomized, Double-blind Study of Dacarbazine With or Without Genasense in Chemotherapy-naive Subjects With Advanced Melanoma and Low LDH (The AGENDA Trial)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00518895
• Other study ID #: AGENDA
• Secondary ID: GM307
• Status: Completed
• Phase: Phase 3
• First received: August 14, 2007
• Last updated: November 4, 2011
• Start date: July 2007
• Est. completion date: May 2011

Study information

• Verified date: April 2009
• Source: Genta Incorporated
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

This study is being performed to prospectively determine whether dacarbazine plus Genasense is significantly better than dacarbazine plus placebo in chemotherapy-naive patients with advanced melanoma and low baseline LDH (LDH less than or equal to 0.8 times the upper limit of normal). LDH is a biomarker strongly associated with improved outcomes in a recent trial of dacarbazine plus Genasense.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 300
• Est. completion date: May 2011
• Est. primary completion date: May 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Histologically confirmed diagnosis of melanoma

• Progressive disease that is not surgically resectable, or metastatic Stage IV

• Low-normal LDH, defined as = 0.8 times the upper limit of normal

• No prior chemotherapy

• Measurable disease

• ECOG performance status = 1

• At least 4 weeks and recovery from effects of major prior surgery or other therapy, including immunotherapy, radiation therapy, or cytokine, biologic or vaccine therapy

• Prior immunotherapy allowed

• Adequate organ function

Exclusion Criteria:

• Prior cytotoxic chemotherapy, including regional perfusion, or prior Genasense treatment

• Primary ocular or mucosal melanoma

• Bone-only metastatic disease

• History or presence of brain metastasis or leptomeningeal disease

• Significant medical disease other than cancer

• Organ allograft

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Melanoma

Intervention

Drug:
• dacarbazine plus Genasense
Protocol therapy will be administered in 21-day cycles for up to 8 cycles. Subjects in the dacarbazine plus Genasense group will receive Genasense 7 mg/kg/day by continuous intravenous infusion beginning on Day 1 and continuing for 5 days (120 hours) plus dacarbazine 1000 mg/m2 as a 60-minute intravenous infusion immediately following the conclusion of the Genasense infusion. Subjects who are responding or have stable disease after 8 cycles of therapy may, at the Investigator's discretion, continue that same therapy for up to 8 additional cycles.
• dacarbazine plus placebo
Protocol therapy will be administered in 21-day cycles for up to 8 cycles. Subjects in the dacarbazine plus placebo group will receive placebo (that is, locally available commercial 0.9% Sodium Chloride Injection) by continuous intravenous infusion beginning on Day 1 and continuing for 5 days (120 hours) plus dacarbazine 1000 mg/m2 as a 60-minute intravenous infusion immediately following the conclusion of the placebo infusion. Subjects who are responding or have stable disease after 8 cycles of therapy may, at the Investigator's discretion, continue that same therapy for up to 8 additional cycles.

Locations

Country	Name	City	State
Australia	Sydney Cancer Center, Royal Prince Alfred Hospital	Camperdown	New South Wales
Australia	Calvary Mater Newcastle	Newcastle	New South Wales
Australia	Westmead Hospital	Westmead	New South Wales
Austria	Universitatsklinik fur Dermatologie und Venerologie, Medizinische Universitat Innsbruck	Innsbruck
Austria	Landesklinikum St. Polten	St. Polten
Austria	Medical University of Vienna, Vienna General Hospital	Wien
Canada	London Regional Cancer Program	London	Ontario
Canada	Princess Margaret Hospital	Toronto	Ontario
Czech Republic	Charles University, Dermatology Department	Prague
France	CHU Saint Jacques	Besancon
France	Hopital Saint-Andre	Bordeaux
France	CHU Ambroise Pare	Boulogne-Billancourt
France	CHU Hotel Dieu	Clermont Ferrand
France	CHU de Dijon, Hopital du Bocage Sud	Dijon
France	CHU de Grenoble, Hopital Albert Michallon	Grenoble
France	Centre Hospitalier du Mans	Le Mans
France	CHRU de Lille, Hopital Claude Huriez	Lille
France	Hopital de l'Hotel Dieu	Lyon
France	Hopital Sainte Marguerite	Marseille
France	Hopital Saint Eloi	Montpellier
France	CHU Hotel Dieu	Nantes
France	Hopital Saint-Louis	Paris
France	Hopital Robert Debre	Reims
France	CHU CH Nicolle	Rouen
France	Institut Gustave Roussy	Villejuif
Germany	Charite Universitatsmedizin Berlin	Berlin
Germany	Vivantes Klinikum im Friedrichshain	Berlin
Germany	Vivantes Klinikum Neukoln, Klinik fur Dermatologie und Venerologie	Berlin
Germany	Klinik fur Dermatologie und Allergologie der Ruhr-Universitat Bochum	Bochum
Germany	Helios Klinikum Erfurt	Erfurt
Germany	Klinik fur Dermatologie, Allergologie und Venerologie, Universitatsklinikum Essen	Essen
Germany	Universitatsklinikum Freiburg	Freiburg
Germany	Hautklinik Linden	Hannover
Germany	Klinikum der Friedrich-Schiller-Universitat Jena	Jena
Germany	Klinik und Poliklinik fur Dermatologie und Venerologie	Koln
Germany	Universitatklinikum A. o. R.	Leipzig
Germany	Hospital of the University of Schleswig-Holstein	Lubeck
Germany	Universitats-Hautklinik Mainz	Mainz
Germany	Universitatsklinikum Mannheim	Mannheim
Germany	Universitatsklinikum Giessen und Marburg GmbH, Klinik fur Dermatologie und Allergologie	Marburg
Germany	Klinik und Poliklinik fur Hautkrankheiten	Munster
Germany	Helios Vogtland-Klinikum Plauen	Plauen
Germany	Klinikum Quedlinburg	Quedlinburg
Germany	Dermatologische Klinik und Poliklinik	Regensburg
Germany	Hautklinik Universitat Tubingen	Tubingen
Italy	Ospedale San Salvatore	Coppitto-L'Aquila
Italy	Istituto Nazionale dei Tumori	Milano
Italy	Istituto Nazionale dei Tumori "G. Pascale"	Napoli
Italy	IFO Instituto Regina-Elena - IRCCS	Rome
Italy	Istituto Dermopatico dell'Immacolata	Rome
Italy	Azienda Ospedaliera Universitaria di Siena	Siena
Poland	Szpital Akademii Medycznej w Gdansku	Gdansk
Poland	Wielkopolskie Centrum Onkologii	Poznan
Spain	Hospital Clinic I Provincial de Barcelona	Barcelona
Spain	Hospital Germans Trias I Pujol	Barcelona
Spain	Hospital Gregorio Maranon	Madrid
Spain	Clinica Universitaria de Navarra	Navarra
Switzerland	University Hospital Zurich	Zurich
United Kingdom	Guy's Hospital	London
United Kingdom	The Royal Marsden Hospital	London
United Kingdom	Christie Hospital	Manchester
United Kingdom	Nottingham University Hospitals NHS Trust, City Campus	Nottingham
United Kingdom	Weston Park Hospital	Sheffield
United States	St. Luke's Cancer Center	Bethlehem	Pennsylvania
United States	Hematology Oncology Centers of the Northern Rockies	Billings	Montana
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	Texas Oncology - Sammons Cancer Center	Dallas	Texas
United States	San Diego Pacific Oncology and Hematology Associates Inc.	Encinitas	California
United States	MD Anderson Cancer Center at University of Texas	Houston	Texas
United States	The West Clinic	Memphis	Tennessee
United States	University of South Alabama Hospital, Mitchell Cancer Institute	Mobile	Alabama
United States	Morristown Memorial - Atlantic Healthcare System	Morristown	New Jersey
United States	Cancer Care Associates	Oklahoma City	Oklahoma
United States	Thomas Jefferson University Hospital	Philadelphia	Pennsylvania
United States	Redwood Regional Medical Group, Inc.	Santa Rosa	California
United States	Siouxland Hematology Oncology Associates	Sioux City	Iowa
United States	Cancer Care Associates, Site 1	Tulsa	Oklahoma

Sponsors (1)

Lead Sponsor	Collaborator
Genta Incorporated

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Canada,  Czech Republic,  France,  Germany,  Italy,  Poland,  Spain,  Switzerland,  United Kingdom, 

References & Publications (2)

Bedikian AY, Agarwala SS, Gilles E, Itri L, Kay R, Garbe C. The AGENDA Study: A randomized, double-blind study of Genasense plus dacarbazine (DTIC) in chemotherapy-naïve subjects with advanced melanoma and low LDH. Pigment Cell Res. 2007;20:538 [Abstract T-26].

Bedikian AY, Millward M, Pehamberger H, Conry R, Gore M, Trefzer U, Pavlick AC, DeConti R, Hersh EM, Hersey P, Kirkwood JM, Haluska FG; Oblimersen Melanoma Study Group. Bcl-2 antisense (oblimersen sodium) plus dacarbazine in patients with advanced melanoma: the Oblimersen Melanoma Study Group. J Clin Oncol. 2006 Oct 10;24(29):4738-45. Epub 2006 Sep 11. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free survival and overall survival		Every 42 days from date of randomization during protocol therapy	No
Secondary	Response rate, durable response rate, duration of response, safety		Response and progression every 42 days from date of randomization during protocol therapy	Yes