Clinical Trials Register

Summary
EudraCT Number:	2013-000548-25
Sponsor's Protocol Code Number:	PM1183-B-004-13
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:	2013-07-01
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

2013-000548-25

A.3

Full title of the trial

A Randomized-Controlled Three-arm Phase II Study of Lurbinectedin (PM01183) Alone or In Combination with Gemcitabine and a control arm with Docetaxel as Second-Line Treatment in Unresectable Non-Small Cell Lung Cancer (NSCLC) Patients.

Studio di fase II, controllato e randomizzato, a tre braccia di Lurbinectedin (PM01183) in monoterapia o associato a Gemcitabina ed un braccio di controllo con Docetaxel come trattamento di seconda linea, in pazienti affetti da carcinoma polmonare non a piccole cellule (NSCLC) in stadio avanzato.

A.3.1

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

A Clinical Study in Three-arm of Lurbinectedin (PM01183) alone or in combination with Gemcitabine and a control arm with Docetaxel as second-line treatment in Small Cell Lung Cancer (NSCLC) patients.

Studio a tre braccia di Lurbinectedin (PM01183) in monoterapia o associato a Gemcitabina ed un braccio di controllo con Docetaxel come trattamento di seconda linea, in pazienti affetti da carcinoma polmonare non a piccole cellule (NSCLC).

A.3.2

Name or abbreviated title of the trial where available

Not applicable

A.4.1

Sponsor's protocol code number

PM1183-B-004-13

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	Pharma Mar S.A. Sociedad Unipersonal
B.1.3.4	Country	Spain
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	Pharma Mar, S.A. Sociedad Unipersonal
B.4.2	Country	Spain
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Pharma Mar, S.A. Sociedad Unipersonal
B.5.2	Functional name of contact point	Clinical Trials
B.5.3	Address:
B.5.3.1	Street Address	Avda. De Los Reyes, no 1 Pol. Ind. La Mina
B.5.3.2	Town/ city	Colmenar Viejo (Madrid)
B.5.3.3	Post code	28770
B.5.3.4	Country	Spain
B.5.4	Telephone number	3491846 60 00
B.5.5	Fax number	3491846 60 03
B.5.6	E-mail	clinicaltrials@pharmamar.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	lurbinectedin
D.3.2	Product code	PM01183
D.3.4	Pharmaceutical form	Powder for concentrate for 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	lurbinectedin
D.3.9.1	CAS number	497871-47-3
D.3.9.2	Current sponsor code	PM01183
D.3.9.4	EV Substance Code	SUB31196
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	1
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	lurbinectedin
D.3.9.1	CAS number	497871-47-3
D.3.9.2	Current sponsor code	PM01183
D.3.9.4	EV Substance Code	SUB31196
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	4
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	Comparator
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.2.5	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	Gemcitabine
D.3.2	Product code	Not applicable
D.3.4	Pharmaceutical form	Powder for 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	GEMCITABINE
D.3.9.1	CAS number	95058-81-4
D.3.9.4	EV Substance Code	SUB07892MIG
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: 3
D.1.2 and D.1.3	IMP Role	Comparator
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.2.5	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	Docetaxel
D.3.2	Product code	Not applicable
D.3.4	Pharmaceutical form	Powder for 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	Docetaxel
D.3.9.3	Other descriptive name	DOCETAXEL
D.3.9.4	EV Substance Code	SUB12492MIG
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.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

Unresectable Non-Small Cell Lung Cancer (NSCLC).

E.1.1.1

Medical condition in easily understood language

Unresectable Non-Small Cell Lung Cancer (NSCLC).

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	16.0
E.1.2	Level	PT
E.1.2	Classification code	10061873
E.1.2	Term	Non-small cell lung cancer
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 evaluate the antitumor activity as progression-freesurvival at four months (PFS4) of PM01183 alone or in combination with gemcitabine as second-line treatment in unresectable NSCLC patients, using single agent docetaxel as a reference in the control arm as current standard of care.

E.2.2

Secondary objectives of the trial

*To analyze the following in each of the three treatment arms:
- Time-to-event endpoints, such as: progression-free survival (PFS), overall survival (OS), overall survival rate at 1-year (OS12) and duration of response (DR).
- Antitumor activity, as response rate (RR) evaluated according to the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
- Safety and efficacy profiles of PM01183 alone and in combination with gemcitabine, to be preliminary compared with docetaxel.
- Patients’ quality of life (QoL) assessment.
- To explore the feasibility and safety of a PM01183 maintenance dose in non-progressing NSCLC patients.
- Pharmacokinetics (PK) of PM01183.
- PK/PD (pharmacokinetic/pharmacodynamic)
correlation in PM01183-based treated patients, whenever possible.
*Pharmacogenomics (PGx): To explore potential correlations between molecular parameters found in previous available tumor samples and clinical outcomes
achieved with PM01183-based treatment.

E.2.3

Trial contains a sub-study

Yes

E.2.3.1

Full title, date and version of each sub-study and their related objectives

Pharmacogenomic sub-study.

E.3

Principal inclusion criteria

1) Voluntary written IC of the patient obtained before any study-specific procedure.
2) Histologically or cytologically confirmed unresectable NSCLC.
3) Patients must have failed one prior line of CT-based therapy for unresectable disease.
4) Age between 18 and 75 years, both inclusive.
5) Measurable disease as defined by RECIST v1.1.
6) Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤ 1.
7) Adequate hematological, renal, metabolic and hepatic function:
a) Hemoglobin ≥ 9 g/dl (patients may have received prior red blood cell [RBC] transfusion up to 48 hours before
treatment start, if clinically indicated), absolute neutrophil count (ANC) ≥ 2.0 x 109/l, and platelet count ≥ 100 x 109/l.
b) Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3.0 x upper limit of normal (ULN) (≤ 5.0 x ULN if liver metastases are present).
c) Total bilirubin ≤ ULN, or direct bilirubin ≤ ULN if total bilirubin is > ULN.
d) Albumin ≥ 3.0 g/dl.
e) Calculated creatinine clearance (CrCl) ≥ 30 ml/minute (using Cockcroft and Gault’s formula).
f) Creatine phosphokinase (CPK) ≤ 2.5 x ULN.
8) At least three weeks since the last prior therapy, at least four weeks since completion of any prior radiotherapy and recovery to grade ≤ 1 from any adverse event (AE) derived from previous anticancer treatment, except alopecia, sensory neuropathy, anemia or asthenia (all of which must have recovered to grade ≤ 2) according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE, v.4).
9) Pre-menopausal women must have a negative pregnancy test before treatment start, not be breast feeding and agree to use adequate contraception during the whole length of study participation and for at least six weeks after the last study dose of PM01183.

E.4

Principal exclusion criteria

1) Concomitant diseases/conditions:
a) History (within the last year) or presence of unstable angina, myocardial infarction, symptomatic congestive heart failure or asymptomatic with left ventricular ejection fraction (LVEF) ≤ 50% (assessed by multiple-gated acquisition scan [MUGA] or equivalent by ultrasound [US]) or clinically significant valvular heart disease.
b) Patients with dyspnea at rest or requiring any oxygen support within the last four weeks.
c) Known infection by human immunodeficiency virus (HIV), including seropositive patients without AIDs.
d) Chronically active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection.
e) Active uncontrolled infection; patients undergoing active antibiotherapy for an ongoing infection must have finished treatment at least one week before treatment start.
f) Pleural or pericardial effusions requiring invasive management procedures.
g) Known myopathy of any cause.
h) Limitation of the patient’s ability to comply with the treatment or to follow-up the protocol.
I) Any other major illness that, in the Investigator’s judgment, will substantially increase the risk associated with the patient’s participation in this study.
2) More than one prior line of CT for advanced or unresectable disease.
3) Histological features of neuroendocrine or bronchioalveolar differentiation.
4) Unknown epidermal growth factor receptor (EGFR) mutation status or previously known EGFR mutated status in patients with adenocarcinoma.
5) Prior or concurrent invasive malignant disease, unless in complete remission for more than three years. Exceptions are completely resected or definitively treated squamous cell carcinoma of the cervix or head and neck without lymphatic spread, cutaneous basal cell carcinoma or superficial transitional cell carcinoma of the bladder.
6) Significant cancer-related weight loss (≥10%) within four weeks prior to treatment start.
7) Prior treatment with gemcitabine or docetaxel-containing therapy (one full infusion at least completed).
8) Symptomatic, steroid-requiring or progressive CNS involvement. If there is prior or current, known or suspected CNS involvement, clinical stability and lack of radiological progression of lesions should be demonstrated for at least the immediate six weeks before study entry.
9) Ongoing symptomatic paraneoplastic syndromes.

E.5 End points

E.5.1

Primary end point(s)

Progression-free survival rate at four months (PFS4), defined as the rate estimate of the percentage of patients
who are alive and progression-free at 16 weeks (~4 months) after randomization.

E.5.1.1

Timepoint(s) of evaluation of this end point

December 2015.

E.5.2

Secondary end point(s)

Overall response rate (ORR), Duration of response (DR), Progression-Free Survival (PFS), Overall Survival (OS), Overall Survival rate at 1 year (OS12), Treatment Safety, Quality of Life (QoL), Non-compartmental (NCA) PK parameters, Pharmacogenomics (PGx).

E.5.2.1

Timepoint(s) of evaluation of this end point

December 2015.

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

E.6.11

Pharmacogenomic

Yes

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

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

E.8.2.3

Other

Yes

E.8.2.3.1

Comparator description

Gemcitabine / Docetaxel

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

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

Nine months after the last treatment discontinuation of the last patient, or twelve months after accrual of the last evaluable patient (whichever occurs first), provided all patients who are still alive have had at least 12 months survival follow-up.

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

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

120

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)

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

2013-07-11

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2013-09-18

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