Clinical Trials Register

Summary
EudraCT Number:	2010-024292-30
Sponsor's Protocol Code Number:	PM1183-B-001-10
National Competent Authority:	UK - MHRA
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2011-03-10
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

UK - MHRA

A.2

EudraCT number

2010-024292-30

A.3

Full title of the trial

A Phase II Study of PM01183 as Second-line Treatment in Patients with Metastatic Pancreatic Cancer

A.3.1

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

Study of PM01183 as Treatment in Patients with Pancreatic Cancer

A.4.1

Sponsor's protocol code number

PM1183-B-001-10

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	Av. de los Reyes, 1. Pol. Ind. "La Mina"
B.5.3.2	Town/ city	Colmenar (Viejo)
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	PM01183
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.3.10	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.3.11 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	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	PM01183
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.3.10	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.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

Metastatic Pancreatic Cancer

E.1.1.1

Medical condition in easily understood language

Pancreatic Cancer

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	LLT
E.1.2	Classification code	10007109
E.1.2	Term	Cancer of pancreas (excl head) metastatic
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

Yes

E.2 Objective of the trial

E.2.1

Main objective of the trial

To evaluate the antitumor activity of PM01183 in terms of overall survival rate at 6 months (OS6) in patients with metastatic pancreatic cancer.

E.2.2

Secondary objectives of the trial

 Progression-free survival (PFS) and progression-free survival rate at three (PFS3) and six months (PFS6).
 Response rate as per the Response Evaluation Criteria in Solid Tumors (RECIST v1.1) and duration of response.
 Tumor marker (CA19-9) evolution during treatment.
 Overall survival (OS) and overall survival rate at 12 months (OS12).
 Safety evaluation in this patient population.
 Pharmacokinetic (PK) analysis in this patient population.
 PK/PD (pharmacokinetic/pharmacodynamic) correlation, if applicable.
 To evaluate the pharmacogenomics (PGx) in prior available tumor samples of treated patients with PM01183 in order to assess potential biomarkers of sensitivity or resistance to PM01183.

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 study (PGx) to evaluate tumor samples of treated patients with PM01183 in order to assess potential biomarkers of sensitivity or resistance to PM01183.

E.3

Principal inclusion criteria

1. Voluntary written informed consent (IC) of the patient obtained before any study-specific procedure.
2. Histologically or cytologically confirmed cancer of the exocrine pancreas.
3. Stage IV disease.
4. Patient must have progressed during or after one prior line of gemcitabine-based therapy.
5. Age ≥ 18 and ≤ 75 years.
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, if clinically indicated); absolute neutrophil count (ANC) ≥ 1.5 x 109/l, and platelet count ≥ 80 x 109/l
b. Alanine aminotransferase (ALT), and aspartate aminotransferase (AST) ≤ 3.0 x upper limit of normality (ULN) (≤ 5.0 ULN if liver metastases are present)
c. Total bilirubin ≤ 1.5 x ULN and direct bilirubin ≤ ULN
d. International Normalized Ratio (INR) <1.5 (except if patient is on oral anticoagulation therapy)
e. Albumin ≥ 3.0 g/dl
f. Calculated creatinine clearance (CrCl)≥30 ml/min (according to the Cockcroft and Gault´s formula)
g. Creatine phosphokinase (CPK) ≤ 2.5 x ULN
8. No prior or concurrent malignant disease unless in complete remission for more than three years, except for adequately treated in situ carcinoma of the cervix, basal or squamous skin cell carcinoma, or in situ transitional bladder cell carcinoma.
9. At least two weeks since last prior therapy (at least four weeks since completion of radiotherapy, if applicable) and recovery to grade ≤ 1 from any adverse event (AE) derived from previous anticancer treatment (excluding alopecia and/or skin toxicity of any grade and asthenia and/or peripheral neuropathy, both grade ≤ 2) according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE, version 4).
10. Women of childbearing potential must have a negative serum pregnancy test before study entry. Both women and men must agree to use a medically acceptable method of contraception throughout the treatment period and for six weeks after discontinuation of treatment.

E.4

Principal exclusion criteria

1. Prior treatment with PM01183.
2. Neuroendocrine differentiation or mucinous subtype on histology.
3. More than one prior systemic line of therapy for advanced disease.
4. Documented brain metastases or leptomeningeal disease involvement.
5. Concomitant diseases/conditions:
a. History, within last year, or presence of unstable angina, myocardial infarction, symptomatic congestive heart failure or asymptomatic left ventricular ejection fraction
(LVEF) ≤45% (assessed by multiple-gated acquisition scan [MUGA] or equivalent by ultrasound [US]) or clinically significant valvular heart disease.
b. Generalized edemas and/or ascites of grade ≥3
c. Immunocompromised patients, including those known to be infected by human immunodeficiency virus (HIV)
d. Chronically active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection
e. Active uncontrolled infection
f. Myopathy or persistent CPK elevations > 2.5 x ULN in two different determinations performed one week apart
g. Limitation of the patient’s ability to comply with the treatment or to follow-up the protocol
h. Any other major illness that, in the Investigator’s judgment, will substantially increase the risk associated with the patient’s participation in this study
6. Uncontrolled ongoing deep venous thrombosis (DVT).
7. Men or women of childbearing potential who are not using an effective method of contraception as previously described; women who are pregnant or breast feeding.
8. Treatment with any investigational product within the period ≤ 5 half-lives prior to the first infusion of PM01183.

E.5 End points

E.5.1

Primary end point(s)

Overall Survival at 6 months, defined as the percentage of patients who are alive six months after the first treatment dose.

E.5.1.1

Timepoint(s) of evaluation of this end point

Along the study durantion

E.5.2

Secondary end point(s)

Overall response rate
Duration of response
Progression Free Survival at 3 and 6 months after the first infusion.
Overall Survival at 12 months
Treatment safety
Pharmacokinetics and Pharmacokinetic/Pharmacodynamic correlation
Pharmacogenomics

E.5.2.1

Timepoint(s) of evaluation of this end point

Along the study durantion

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

E.8.1.1

Randomised

Information not present in EudraCT

E.8.1.2

Open

Information not present in EudraCT

E.8.1.3

Single blind

Information not present in EudraCT

E.8.1.4

Double blind

Information not present in EudraCT

E.8.1.5

Parallel group

Information not present in EudraCT

E.8.1.6

Cross over

Information not present in EudraCT

E.8.1.7

Other

Information not present in EudraCT

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.8.3

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

E.8.6.2

Trial being conducted completely outside of the EEA

Information not present in EudraCT

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

Planned study termination or end of study (EOS) (clinical cutoff) will be nine months after the last patient-last treatment visit in the study, or twelve months after the last patient is included (whichever occurs first).

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

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)

Not applicable

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

2011-04-05

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2011-09-05

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2013-11-28

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