Clinical Trials Register

Summary
EudraCT Number:	2013-002291-41
Sponsor's Protocol Code Number:	CC-486-MEL-001
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2013-11-28
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

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A. Protocol Information

A.1

Member State Concerned

Italy - Italian Medicines Agency

A.2

EudraCT number

2013-002291-41

A.3

Full title of the trial

A Randomized, Open Label, Multi-Center Phase 2 Study of nab-Paclitaxel versus Epigenetic Modifying Therapy of CC-486 with nab-Paclitaxel in Subjects with Chemotherapy Naïve Metastatic Melanoma

A.3.1

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

A study in which nab-paclitaxel will be compared to CC-486 with nab-paclitaxel in patients with melanoma which has spread to other organs who have not received chemotherapy

A.4.1

Sponsor's protocol code number

CC-486-MEL-001

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT01933061

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	Celgene Corporation
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	Celgene Corporation
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Celgene Corporation
B.5.2	Functional name of contact point	ClinicalTrialDisclosure
B.5.3	Address:
B.5.3.1	Street Address	9225 Indian Creek Parkway, Suite 900
B.5.3.2	Town/ city	Overland Park, Kansas
B.5.3.3	Post code	66210
B.5.3.4	Country	United States
B.5.4	Telephone number	+1 888 260 1599
B.5.5	Fax number	+1 913 266 0394
B.5.6	E-mail	ClinicalTrialDisclosure@celgene.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	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	Oral Azacitidine
D.3.2	Product code	CC-486
D.3.4	Pharmaceutical form	Film-coated tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	AZACITIDINE
D.3.9.1	CAS number	320-67-2
D.3.9.4	EV Substance Code	SUB05624MIG
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)	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	No
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	Abraxane 5 mg/ml powder for suspension for infusion
D.2.1.1.2	Name of the Marketing Authorisation holder	Celgene Europe Limited
D.2.1.2	Country which granted the Marketing Authorisation	European Union
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	Powder for suspension for injection
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	PACLITAXEL
D.3.9.1	CAS number	33069-62-4
D.3.9.2	Current sponsor code	nab-paclitaxel
D.3.9.4	EV Substance Code	SUB09583MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	5
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)	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	The IMP contains an excipient of biological origin, albumin, a non-active stabilising agent. It is derived from human blood subject to approved donor screening and product manufacturing processes.

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

Chemotherapy naïve metastatic melanoma.

E.1.1.1

Medical condition in easily understood language

Patients with melanoma skin cancer (a type of skin cancer) that has spread to other organs and who have not received prior chemotherapy.

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	10025671
E.1.2	Term	Malignant melanoma stage IV
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 compare treatment arms with respect to antitumor activity as measured by progression-free survival (PFS)

E.2.2

Secondary objectives of the trial

To compare:
- Overall Survival (OS);
- Objective response rate (ORR);
- Disease Control Rate (DCR);
- Duration of response
and to define the safety and tolerability of nab-paclitaxel when administered after CC-486 epigenetic modifying therapy .

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Histologically or cytologically confirmed cutaneous BRAF wild-type
malignant melanoma with evidence of metastasis (Stage IV).
2. No prior cytotoxic chemotherapy for metastatic malignant melanoma
is permitted. No prior adjuvant cytotoxic chemotherapy is permitted.
● Up to one prior regimen with the following classes of agents is
permitted:
o Targeted biologic agents (e.g. interleukin 2 [IL-2], granulocyte macrophage colony stimulating factor [GM-CSF], other cytokines or unarmed monoclonal antibodies)
o Targeted small molecule inhibitors (e.g., kinase inhibitors, heat shock protein [HSP] inhibitors, etc.).
o Immune checkpoint inhibitors (e.g. anti-CTLA4, anti-PD1, anti-PDL1).
o Prior adjuvant therapy with interferon and/or vaccines is permitted.
● Prior treatments should be completed 4 weeks prior to enrollment in the study (ie, randomization).
3. Male or non-pregnant and non-lactating female, and ≥ 18 years of age at the time of signing the informed consent document.
● If heterosexually active, the subject must agree to use medical doctor-approved contraception throughout the study, and for 6 months after last dose of study drug.
4. History of malignancy in the last 5 years; subjects with prior history of in situ cancer or basal or squamous cell skin cancer are eligible.
● Subjects with other malignancies are eligible if they were cured by surgery (with or without radiotherapy) and have been continuously disease-free for at least 5 years.
5. Radiographically-documented measurable disease (defined by the presence of at least one radiographically documented measurable lesion including measurable cutaneous metastasis).
6. Adequate haemtological and biochemical parameters:
● ANC ≥ 1.5 x 109 cells/L.
● Platelets ≥ 100 x 109 cells/L.
● Hgb ≥ 9 g/dL.
● AST (SGOT) or ALT (SGPT) ≥ 2.5x upper limit of normal range (ULN);
o ≤ 5.0 x ULN if hepatic metastases present.
● Total bilirubin ≤ ULN.
● Creatinine ≤ 1.5 mg/dL.
7. ECOG performance status 0 to 1.

E.4

Principal exclusion criteria

1. History of or current evidence of symptomatic brain metastases (brain Computed Tomography (CT)/Magnetic Resonance Imaging (MRI) is needed to exclude brain metastasis), including leptomeningeal involvement.
2. Subject has pre-existing peripheral neuropathy of National Cancer Institute NCI Common Terminology Criteria for Adverse Events (NCI CTCAE) Scale of Grade ≥ 2.
3. Prior radiation to a target lesion is permitted only if there has been clear progression of the lesion since radiation was completed.

E.5 End points

E.5.1

Primary end point(s)

Progression-free survival (PFS) based on a blinded radiology assessment of response

E.5.1.1

Timepoint(s) of evaluation of this end point

Response assessments for each subject every 6 weeks until documented disease progression. At least 62 PFS events are required for the final analysis.

E.5.2

Secondary end point(s)

- Overall survival.
- Progression-free survival based on investigator assessment.
- Number (%) of subjects who achieve an objective complete or partial response (objective response rate [ORR])
- Number (%) of subjects with SD for ≥ 18 weeks, or complete or partial response (disease control rate (DCR)).
- Duration of response in responding subjects.
- Incidence and severity of neutropenia and other hematologic and non-hematologic treatment-emergent adverse events (AEs) and serious adverse events (SAEs), laboratory abnormalities.
- Incidence of subjects experiencing dose modifications, dose interruptions, and/or premature discontinuation of study drug.

E.5.2.1

Timepoint(s) of evaluation of this end point

Safety related endpoints (incidence and severity of neutropenia, other hematologic, non-hematologic treatment-emergent AEs and SAEs, lab. abnormalities; incidence of subjects experiencing dose modifications, interruptions, and/or premature discontinuation of IMP) will be evaluated on an ongoing basis.
Subject survival will be monitored on a monthly basis for 6 months from discontinuation from the study and every 3 months thereafter, until death or study termination in all subjects.
Response related endpoints (PFS based on Inv. assessment; % of subjects who achieve ORR; % of subjects with SD for ≥ 18 weeks, complete or partial response; duration of response) will be evaluated every 6 weeks from the start of treatment until progressive disease is documented.

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

Yes

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

Yes

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

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

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)

Yes

E.8.2.2

Placebo

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

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.8.5.1

Number of sites anticipated in the EEA

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

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

France

Germany

Italy

United Kingdom

United States

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

Either as the date of the last visit of the last subject to complete the study, or the date of receipt of the last data point from the last subject that is required for primary, secondary and/or exploratory analysis, as pre-specified in the protocol and/or the Statistical Analysis Plan (SAP), whichever is the later date.

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

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

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

Yes

F.3.3.6.1

Details of subjects incapable of giving consent

Consent signed by legally authorized representative: see inclusion criterion #10, protocol section 7.2.

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

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)

After the subject has ended the participation in the trial he or she will receive standard of care.

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

2014-01-19

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2013-12-17

P. End of Trial
P.	End of Trial Status	Prematurely Ended

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