Clinical Trials Register

Summary
EudraCT Number:	2007-003340-30
Sponsor's Protocol Code Number:	GM307
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2008-02-20
Trial results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Italy - Italian Medicines Agency

A.2

EudraCT number

2007-003340-30

A.3

Full title of the trial

A multicenter, randomized, double-blind study of dacarbazine with or without Genasense in chemotherapy naïve subjects with advanced melanoma and low LDH (The AGENDA Trial)

A.3.2

Name or abbreviated title of the trial where available

AGENDA

A.4.1

Sponsor's protocol code number

GM307

A.5.1

ISRCTN (International Standard Randomised Controlled Trial) Number

A.7

Trial is part of a Paediatric Investigation Plan

Information not present in EudraCT

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Genta Incorporated
B.1.3.4	Country	United States
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support
B.4.2	Country
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation
B.5.2	Functional name of contact point

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Genasense
D.3.2	Product code	GM307
D.3.4	Pharmaceutical form	Solution for infusion
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	OBLIMERSEN
D.3.9.1	CAS number	190977-41-4
D.3.9.2	Current sponsor code	oblimersen, G3139
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	300
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	Information not present in EudraCT
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	Information not present in EudraCT
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	Information not present in EudraCT
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	Yes
D.3.11.13.1	Other medicinal product type	Non Applicabile
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Information not present in EudraCT
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Dacarbazine
D.3.4	Pharmaceutical form	Powder and solvent for solution for infusion
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Dacarbazine
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	100
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	Information not present in EudraCT
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	Information not present in EudraCT
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	Information not present in EudraCT
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	Yes
D.3.11.13.1	Other medicinal product type	Non Applicabile

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Solution for infusion
D.8.4	Route of administration of the placebo	Intravenous use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

naïve subjects with advanced melanoma and low LDH.

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	9.1
E.1.2	Level	LLT
E.1.2	Classification code	10025650
E.1.2	Term	Malignant melanoma

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

The primary objective of this study is to compare progression-free survival and overall survival in the dacarbazine plus Genasense treatment group and the dacarbazine plus placebo treatment group.

E.2.2

Secondary objectives of the trial

The secondary objectives of this study are to compare the 2 treatment groups with respect to the percentages of subjects with response and durable response, duration of response, and the safety of the 2 treatment regimens.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

The following criteria must be met before registration not more than 15 days prior to randomisation: 1. Histologically confirmed diagnosis of melanoma 2. Progressive disease that is not surgically resectable, or metastatic Stage IV disease 3. LDH </= 0.8 x ULN 4. Chemotherapy naïve Note: Prior immunotherapy, radiotherapy, or cytokine, biologic, or vaccine therapy is permitted. 5. Measurable disease defined as at least 1 tumor lesion that can be accurately and serially measured in at least 1 dimension (longest diameter to be recorded) and is >/= 20 mm with conventional techniques and >/= 10 mm with spiral CT, based on Response Evaluation Criteria in Solid Tumors (RECIST) Lesions that are considered nonmeasurable include: Bone lesions, Ascites and pleural/pericardial effusions; Lymphangitis cutis/pulmonis ; Abdominal masses not confirmed and not followed by imaging studies; Cystic lesions; Tumors treated by irradiation or intra-tumor injection therapy without progression in that area or measurable disease outside that area 6. ECOG performance status </= 1 7. At least 4 weeks and recovery from effects of prior surgery or other therapy, including immunotherapy, radiotherapy, or cytokine, biologic, or vaccine therapy 8. Adequate organ function, defined as: a. Absolute neutrophil count (ANC) >/= 1500/mm3 b. Platelet count >/= 100,000/mm3 c. Hemoglobin >/= 11 g/dL without need for hematopoietic growth factor or transfusion support d. Serum creatinine </= 1.5 x ULN or 24-hour creatinine clearance >/= 50 mL/min e. Serum bilirubin </= 1.5 x ULN f. Aspartate aminotransferase (AST) </= 2.5 x ULN g. Alanine aminotransferase (ALT) </= 2.5 x ULN h. Alkaline phosphatase </= 2.5 x ULN i. Serum albumin >/= 3.0 g/dL j. Prothrombin time (PT) </= 1.5 x ULN (or international normalized ratio [INR] </= 1.3) k. Partial thromboplastin time (PTT) </= 1.5 x ULN 9. At least 18 years of age 10. Venous access adequate to maintain a 5-day continuous intravenous infusion 11. Intellectual, emotional, and physical ability to maintain an ambulatory infusion pump

E.4

Principal exclusion criteria

1. Prior cytotoxic chemotherapy, including regional perfusion, or prior Genasense treatment 2. Need for other anticancer treatment (such as chemotherapy, radiation, or biologic or investigational therapies) while receiving protocol therapy in this study 3. Primary ocular or mucosal melanoma 4. Bone-only metastatic disease 5. History or presence of brain metastasis or leptomeningeal disease 6. History of second cancer (except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer for which the patient has been disease-free for 5 or more years) 7. Significant medical disease other than cancer, such as: uncontrolled congestive heart failure; active symptoms of coronary artery disease (defined as uncontrolled arrhythmias or recurrent chest pain despite prophylactic medication); New York Heart Association Class III or IV disease; cardiovascular signs and symptoms >/= Grade 2 by common toxicity criteria (CTC) during the 4-week period prior to initiation of protocol therapy; uncontrolled seizure disorder; history of chronic hepatitis or cirrhosis; active infection; uncontrolled diabetes mellitus; requirement for chronic corticosteroid treatment with an average dose >/= 20 mg/day of prednisone (or equivalent); requirement for concurrent immunosuppressive drug(s); active autoimmune disease 8. Organ allograft 9. Known human immunodeficiency virus infection 10. Pregnancy or lactation;
- Women of childbearing potential and sexually active males must be advised to take precautions to prevent pregnancy during protocol therapy.
- All subjects must use an effective form of birth control during protocol therapy (except if the women is post menopause for > 1 year or surgically sterile). 11. Known hypersensitivity to dacarbazine or phosphorothioate-containing oligonucleotides 12. Use of any experimental therapy within 3 weeks prior to screening evaluations 13. Need for concomitant anticoagulant therapy with the exception of 1 mg/day of warfarin for central-line prophylaxis

E.5 End points

E.5.1

Primary end point(s)

The primary endpoint is progression-free survival.

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

Yes

E.8.2.3

Other

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

Information not present in EudraCT

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

E.8.7

Trial has a data monitoring committee

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

The end of trial is defined as when the last patient completes 24 months after randomisation.

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

F. Population of Trial Subjects
F.1 Age Range
F.1.1	Trial has subjects under 18	No
F.1.1.1	In Utero	No
F.1.1.2	Preterm newborn infants (up to gestational age < 37 weeks)	No
F.1.1.3	Newborns (0-27 days)	No
F.1.1.4	Infants and toddlers (28 days-23 months)	No
F.1.1.5	Children (2-11years)	No
F.1.1.6	Adolescents (12-17 years)	No
F.1.2	Adults (18-64 years)	Yes
F.1.3	Elderly (>=65 years)	Yes
F.2 Gender
F.2.1	Female	Yes
F.2.2	Male	Yes
F.3 Group of trial subjects
F.3.1	Healthy volunteers	No
F.3.2	Patients	Yes
F.3.3	Specific vulnerable populations	Yes
F.3.3.1	Women of childbearing potential not using contraception For clinical trials recorded in the database before the 10th March 2011 this question read: "Women of childbearing potential" and did not include the words "not using contraception". An answer of yes could have included women of child bearing potential whether or not they would be using contraception. The answer should therefore be understood in that context. This trial was recorded in the database on 2008-02-20.	Yes
F.3.3.2	Women of child-bearing potential using contraception	Information not present in EudraCT
F.3.3.3	Pregnant women	No
F.3.3.4	Nursing women	No
F.3.3.5	Emergency situation	No
F.3.3.6	Subjects incapable of giving consent personally	No
F.3.3.7	Others	No
F.4 Planned number of subjects to be included
F.4.1	In the member state	30
F.4.2	For a multinational trial
F.4.2.1	In the EEA	200
F.4.2.2	In the whole clinical trial	300

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2008-04-03

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2007-10-18

P. End of Trial
P.	End of Trial Status	Ongoing

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