Trial of Dacarbazine With or Without Genasense in Advanced Melanoma - Full Text View

Sponsor:	Genta Incorporated
Information provided by:	Genta Incorporated
ClinicalTrials.gov Identifier:	NCT00518895

Purpose

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.

Condition	Intervention	Phase
Melanoma	Drug: dacarbazine plus Genasense Drug: dacarbazine plus placebo	Phase III

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Active Control, Parallel Assignment, Safety/Efficacy Study
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)

Resource links provided by NLM:

MedlinePlus related topics: Cancer Melanoma

Drug Information available for: Oblimersen sodium Dacarbazine Sodium chloride

U.S. FDA Resources

Further study details as provided by Genta Incorporated:

Primary Outcome Measures:

Progression-free survival and overall survival [ Time Frame: Every 42 days from date of randomization during protocol therapy ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Response rate, durable response rate, duration of response, safety [ Time Frame: Response and progression every 42 days from date of randomization during protocol therapy ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	300
Study Start Date:	July 2007
Estimated Study Completion Date:	March 2011
Estimated Primary Completion Date:	March 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
A: Experimental Dacarbazine with Genasense	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.
B: Active Comparator Dacarbazine with placebo	Drug: 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.

Arms

Assigned Interventions

A: Experimental

Dacarbazine with Genasense

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.

B: Active Comparator

Dacarbazine with placebo

Drug: 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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00518895

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Locations

United States, Alabama
University of South Alabama Hospital, Mitchell Cancer Institute
Mobile, Alabama, United States, 36607
United States, California
San Diego Pacific Oncology and Hematology Associates Inc.
Encinitas, California, United States, 92024
Redwood Regional Medical Group, Inc.
Santa Rosa, California, United States, 95403
United States, Iowa
Siouxland Hematology Oncology Associates
Sioux City, Iowa, United States, 51101
United States, Massachusetts
Dana Farber Cancer Institute
Boston, Massachusetts, United States, 02115
United States, Montana
Hematology Oncology Centers of the Northern Rockies
Billings, Montana, United States, 59101
United States, New Jersey
Morristown Memorial - Atlantic Healthcare System
Morristown, New Jersey, United States, 07960
United States, Oklahoma
Cancer Care Associates
Oklahoma City, Oklahoma, United States, 73112
Cancer Care Associates, Site 1
Tulsa, Oklahoma, United States, 74104
United States, Pennsylvania
Thomas Jefferson University Hospital
Philadelphia, Pennsylvania, United States, 19107
St. Luke's Cancer Center
Bethlehem, Pennsylvania, United States, 18015
United States, Tennessee
The West Clinic
Memphis, Tennessee, United States, 38120
United States, Texas
MD Anderson Cancer Center at University of Texas
Houston, Texas, United States, 77030-4009
Texas Oncology - Sammons Cancer Center
Dallas, Texas, United States, 75246
Australia, New South Wales
Westmead Hospital
Westmead, New South Wales, Australia
Sydney Cancer Center, Royal Prince Alfred Hospital
Camperdown, New South Wales, Australia, 2050
Calvary Mater Newcastle
Newcastle, New South Wales, Australia
Austria
Medical University of Vienna, Vienna General Hospital
Wien, Austria
Universitatsklinik fur Dermatologie und Venerologie, Medizinische Universitat Innsbruck
Innsbruck, Austria
Landesklinikum St. Polten
St. Polten, Austria
Canada, Ontario
London Regional Cancer Program
London, Ontario, Canada
Princess Margaret Hospital
Toronto, Ontario, Canada
Czech Republic
Charles University, Dermatology Department
Prague, Czech Republic
France
Hopital Sainte Marguerite
Marseille, France
CHU CH Nicolle
Rouen, France
Hopital Robert Debre
Reims, France
Institut Gustave Roussy
Villejuif, France
CHU Ambroise Pare
Boulogne-Billancourt, France
CHU Hotel Dieu
Clermont Ferrand, France
Hopital Saint Eloi
Montpellier, France
Hopital Saint-Andre
Bordeaux, France
Hopital Saint-Louis
Paris, France
CHU de Grenoble, Hopital Albert Michallon
Grenoble, France
CHRU de Lille, Hopital Claude Huriez
Lille, France
CHU Saint Jacques
Besancon, France
Centre Hospitalier du Mans
Le Mans, France
CHU de Dijon, Hopital du Bocage Sud
Dijon, France
Hopital de l'Hotel Dieu
Lyon, France
CHU Hotel Dieu
Nantes, France
Germany
Hautklinik Universitat Tubingen
Tubingen, Germany
Klinik fur Dermatologie und Allergologie der Ruhr-Universitat Bochum
Bochum, Germany
Vivantes Klinikum Neukoln, Klinik fur Dermatologie und Venerologie
Berlin, Germany
Klinik und Poliklinik fur Dermatologie und Venerologie
Koln, Germany
Helios Vogtland-Klinikum Plauen
Plauen, Germany
Klinikum Quedlinburg
Quedlinburg, Germany
Klinik fur Dermatologie, Allergologie und Venerologie, Universitatsklinikum Essen
Essen, Germany
Hautklinik Linden
Hannover, Germany
Vivantes Klinikum im Friedrichshain
Berlin, Germany
Universitats-Hautklinik Mainz
Mainz, Germany
Universitatsklinikum Freiburg
Freiburg, Germany
Universitatklinikum A. o. R.
Leipzig, Germany
Klinik und Poliklinik fur Hautkrankheiten
Munster, Germany
Hospital of the University of Schleswig-Holstein
Lubeck, Germany
Charite Universitatsmedizin Berlin
Berlin, Germany
Dermatologische Klinik und Poliklinik
Regensburg, Germany
Universitatsklinikum Giessen und Marburg GmbH, Klinik fur Dermatologie und Allergologie
Marburg, Germany
Universitatsklinikum Mannheim
Mannheim, Germany
Klinikum der Friedrich-Schiller-Universitat Jena
Jena, Germany
Helios Klinikum Erfurt
Erfurt, Germany
Italy
Istituto Dermopatico dell'Immacolata
Rome, Italy
Istituto Nazionale dei Tumori "G. Pascale"
Napoli, Italy
Azienda Ospedaliera Universitaria di Siena
Siena, Italy
Ospedale San Salvatore
Coppitto-L'Aquila, Italy
IFO Instituto Regina-Elena - IRCCS
Rome, Italy
Istituto Nazionale dei Tumori
Milano, Italy
Poland
Wielkopolskie Centrum Onkologii
Poznan, Poland
Szpital Akademii Medycznej w Gdansku
Gdansk, Poland
Spain
Hospital Germans Trias I Pujol
Barcelona, Spain
Clinica Universitaria de Navarra
Navarra, Spain
Hospital Gregorio Maranon
Madrid, Spain
Hospital Clinic I Provincial de Barcelona
Barcelona, Spain
Switzerland
University Hospital Zurich
Zurich, Switzerland
United Kingdom
Christie Hospital
Manchester, United Kingdom
Nottingham University Hospitals NHS Trust, City Campus
Nottingham, United Kingdom
Weston Park Hospital
Sheffield, United Kingdom
The Royal Marsden Hospital
London, United Kingdom
Guy's Hospital
London, United Kingdom

Sponsors and Collaborators

Genta Incorporated

More Information

Additional Information:

Related Info This link exits the ClinicalTrials.gov site

Publications:

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.

Responsible Party:	Genta Incorporated ( Steven Novick, MD, PhD )
Study ID Numbers:	AGENDA, GM307
Study First Received:	August 14, 2007
Last Updated:	April 7, 2009
ClinicalTrials.gov Identifier:	NCT00518895 History of Changes
Health Authority:	United States: Food and Drug Administration

Keywords provided by Genta Incorporated:

Melanoma
Advanced Melanoma
Malignant Melanoma
Metastatic Melanoma
Skin Cancer
Genasense

oblimersen
antisense
Bcl-2 antisense
G3139
dacarbazine

Additional relevant MeSH terms:

Neoplasms by Histologic Type
Dacarbazine
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Neoplasms, Nerve Tissue
Pharmacologic Actions
Melanoma
Neuroendocrine Tumors

Neuroectodermal Tumors
Neoplasms
Therapeutic Uses
Neoplasms, Germ Cell and Embryonal
Nevi and Melanomas
Antineoplastic Agents, Alkylating
Alkylating Agents

ClinicalTrials.gov processed this record on November 27, 2009