Clinical Trials Register

Summary
EudraCT Number:	2005-003416-30
Sponsor's Protocol Code Number:	ML18727
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2006-03-15
Trial results	View 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

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

Italy - Italian Medicines Agency

A.2

EudraCT number

2005-003416-30

A.3

Full title of the trial

Phase II study of Dacarbazine with the anti-vascular endothelial growth factor antibody (Bevacizumab) in patients with unresectable/metastatic melanoma.

Studio di fase II sull`associazione di Dacarbazina e l`anticorpo anti-fattore di crescita dell`endotelio vascolare (Bevacizumab) in pazienti con melanoma non resecabile/metastatico.

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

A.3.2

Name or abbreviated title of the trial where available

Avastin+DTIC in Melanoma

A.4.1

Sponsor's protocol code number

ML18727

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	ROCHE
B.1.3.4	Country	Italy
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	ROCHE S.p.A.
B.4.2	Country	Italy
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Roche S.p.A.
B.5.2	Functional name of contact point	Medical Affairs&Clinical Operations
B.5.3	Address:
B.5.3.1	Street Address	V.le G. B. Stucchi, 110
B.5.3.2	Town/ city	Monza
B.5.3.3	Post code	20900
B.5.3.4	Country	Italy
B.5.4	Telephone number	0392475070
B.5.5	Fax number	0392475085
B.5.6	E-mail	ITALY.INFO_CTA@ROCHE.COM

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	Yes
D.2.1.1.1	Trade name	Avastin
D.2.1.1.2	Name of the Marketing Authorisation holder	ROCHE REGISTRATION LTD
D.2.1.2	Country which granted the Marketing Authorisation	United Kingdom
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.3.4	Pharmaceutical form	Solution for infusion
D.3.4.1	Specific paediatric formulation	No
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	Bevacizumab
D.3.9.1	CAS number	216974-75-3
D.3.9.2	Current sponsor code	RO 4876646-000
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.3	Concentration number	100
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
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	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
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	No
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	Yes
D.2.1.1.1	Trade name	Avastin
D.2.1.1.2	Name of the Marketing Authorisation holder	ROCHE REGISTRATION LTD
D.2.1.2	Country which granted the Marketing Authorisation	United Kingdom
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.3.4	Pharmaceutical form	Solution for infusion
D.3.4.1	Specific paediatric formulation	No
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	Bevacizumab
D.3.9.1	CAS number	216974-75-3
D.3.9.2	Current sponsor code	RO 4876646-000
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.3	Concentration number	400
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
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	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
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	No
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

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Patients with clinical evidence of metastatic melanoma and/or unresectable regional lymphatic disease and/or extensive in transit recurrent disease.

Pazienti con evidenza clinica di melanoma metastatico e/o metastasi linfatica regionale non resecabile e/o malattia estensiva ricorrente

E.1.1.1

Medical condition in easily understood language

Metastatic melanoma

Melanoma metastatico

E.1.1.2

Therapeutic area

Diseases [C] - Cancer [C04]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	14.1
E.1.2	Level	PT
E.1.2	Classification code	10027480
E.1.2	Term	Metastatic malignant melanoma
E.1.2	System Organ Class	10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

To assess the preliminary antitumor activity in terms of overall response rate (complete and partial responses) of bevacizumab in combination with dacarbazine.

Determinare il tasso globale di risposte obiettive (risposte complete e parziali) in pazienti con melanoma non resecabile/metastatico trattati con bevacizumab in associazione a dacarbazina.

E.2.2

Secondary objectives of the trial

- To evaluate toxicity and the safety profile of the combination. - To evaluate duration of response (DR), time to progression (TTP), time to treatment failure (TTF) and overall survival.

- Valutare il profilo di tossicita` e sicurezza della combinazione.- Valutare la durata della risposta (DR),il tempo alla progressione (TTP),il tempo al fallimento terapeutico (TTF) e la sopravvivenza globale (OS).

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Histologically or cytologically confirmed cutaneous malignant melanoma 2. Clinical evidence of metastatic disease and/or unresectable regional lymphatic disease and/or extensive in transit recurrent disease 3. Age ≥ 18 4. ECOG Performance Status 0-1 5. Life expectancy of at least 12 weeks 6. Measurable and/or evaluable lesions according to RECIST criteria 7. Laboratory requirements: − Neutrophils ≥1.5 x 109/L and Platelets ≥100 x 109/L − Total bilirubin ≤1.5 time the upper-normal limits (UNL) of the Institutional normal values and ASAT (SGOT) and/or ALAT (SGPT) ≤2.5 x UNL, or ≤5 x UNL in case of liver metastases, alkaline phosphatase ≤2.5 x UNL, ≤ 5 x UNL in case of liver metastases, ≤10 x UNL in case of bone metastases. − Creatinine clearance >50 mL/min or serum creatinine ≤1.5 x UNL) − Urine dipstick of proteinuria <2+. Patients discovered to have ≥2+ proteinuria on dipstick urinalysis at baseline, should undergo a 24-hour urine collection and must demonstrate ≤1 g of protein/24 hr. 8. Written informed consent. 9. Patients must be accessible for treatment and follow up. Patients registered on this trial must be treated and followed at the participating center

1. Melanoma maligno confermato citologicamente o istologicamente 2. Malattia metastatica e/o malattia linfonodale non resecabile e/o malattia in transit non resecabile 3. Eta` > 18 4. ECOG Performance Status 0-1 5. Attesa di vita di almeno 12 settimane 6. Lesioni misurabili e/o valutabili secondo i criteri RECIST 7. Parametri di laboratorio:  Neutrofili >1.5 x 109/L e Piastrine >100 x 109/L  Bilirubina tot. <1.5 volte i limiti di norma (UNL) e ASAT (SGOT) e/o ALAT (SGPT) <2.5 x UNL, o <5 x UNL in caso di metastasi epatiche, fosfatasi alcalina <2.5 x UNL, < 5 x UNL in caso di metastasi epatiche, <10 x UNL in caso di metastasi ossee.  Clearance di creatinina >50 mL/min o creatinina <1.5 x UNL)  Urine dipstick per proteinuria <2+. Pazienti con >2+ proteinuria al dipstick basale, dovrebbero sottoporsi ad una rccolta urine di 24 ore ed avere <1 g di proteine/24 ore. 8. Consenso informato scritto. 9. I pazienti devono poter accedere al centro per i trattamenti e per le visite di follow-up. I pazienti registrati in questo trial devono essere trattati e seguiti dal centro.

E.4

Principal exclusion criteria

1. At least 4 weeks since prior adjuvant therapy with interferon alfa 2. Prior interferon alfa and/or cytokine therapy (e.g., high dose interleukin-2) for metastatic disease 3. Prior investigational antiangiogenic agents 4. Prior chemotherapy regimen for metastatic disease 5. Radiotherapy to any site within 4 weeks before the study. 6. Symptomatic and/or unstable pre-existing brain metastases (CT or MRI of the head is required within 4 weeks prior to treatment start). 7. History of inflammatory bowel disease and/or acute/subacute bowel occlusion. 8. Serious non-healing wound or ulcer. 9. Evidence of bleeding diathesis or coagulopathy. 10. Uncontrolled hypertension. 11. Clinically significant (i.e. active) cardiovascular disease for example cerebrovascular accidents (≤6 months), myocardial infarction (≤ 6 months), unstable angina, New York Heart Association (NYHA) grade II or greater congestive heart failure, serious cardiac arrhythmia requiring medication. 12. Current or recent (within 10 days prior to study treatment start) ongoing treatment with anticoagulants for therapeutic purposes. 13. Chronic, daily treatment with high-dose aspirin (>325 mg/day) or other medications known to predispose to gastrointestinal ulceration. 14. Patients with known allergy to Chinese hamster ovary cell proteins, or any of the components of the study medications 15. Other co-existing malignancies or malignancies diagnosed within the last 5 years with the exception of basal cell carcinoma or cervical cancer in situ 16. Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to study treatment start, or anticipation of the need for major surgical procedure during the course of the study. 17. Pregnant or lactating women. Women of childbearing potential with either a positive or no pregnancy test at baseline. Postmenopausal women must have been amenorrheic for at least 12 months to be considered of non-childbearing potential. Sexually active males and females (of childbearing potential) unwilling to practice contraception during the study.

1. Almeno 4 settimane dall`ultimo trattamento con interferon alfa adiuvante 2. Precedente interferon alfa e/o citochine (e.g., interleukin-2 alte dosi) per la malattia metastatica 3. Precedenti trattamenti sperimentali con agenti anti-angiogenici 4. Precedente chemioterapia per la malattia metastatica 5. Radioterapia entro 4 settimane prima dello studio 6. Metastasi cerebrali sintomatiche 7. Anamnesi di malattia infiammatorie dell`intestino e/o occlusione intestina acuta/subacuta. 8. Ulcere o ferite che non guariscono 9. Evidenza di sanguinamento e di coagulopatia 10. Ipertensione incontrollata 11. Patologie cardiovascolari clinicamente significative 12. Trattamento in corso o recente (entro 10 giorni dall`inizio della terapia) con anticoagulanti a fini terapeutici. 13. Alte dosi quotidiane croniche di aspirina (>325 mg/die) o altre medicamenti che predispongono a ulcerazione gastrointestinali. 14. Pazienti allergici alle proteine delle cellule ovariche di hamster cinese 15. Altre neoplsie diagnosticate negli ultimi 5 anni eccetto basalioma o carcinoma in situ della cervice. 16. Chirurgie maggiori, biopsie a cielo aperto, o lesioni traumatiche significative negli ultimi 28 giorni prima del trattamento oppure necessita` di chirurgia maggiore durante lo studio. 17. Donne gravide o in allattamento

E.5 End points

E.5.1

Primary end point(s)

Best tumor response at any time during therapy.

Migliore risposta al trattamento in qualsiasi fase della terapia

E.5.1.1

Timepoint(s) of evaluation of this end point

E.5.2

Secondary end point(s)

E.5.2.1

Timepoint(s) of evaluation of this end point

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)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

E.8.1.1

Randomised

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

Yes

E.8.1.7.1

Other trial design description

studio prospettico, in aperto

...

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

Information not present in EudraCT

E.8.2.2

Placebo

Information not present in EudraCT

E.8.2.3

Other

Information not present in EudraCT

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

Yes

E.8.4

The trial involves multiple sites in the Member State concerned

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

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

End of study: 6 months after the last treatment of the last treated patient.

Fine studio: 6 mesi dopo l`ultimo trattamento dell`ultimo paziente

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

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1

Number of subjects for this age range:

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

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

2006-02-22

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2006-01-11

P. End of Trial
P.	End of Trial Status	Completed

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials