Clinical Trials Register

Summary
EudraCT Number:	2015-002816-34
Sponsor's Protocol Code Number:	2015/8463
National Competent Authority:	Norway - NOMA
Clinical Trial Type:	EEA CTA
Trial Status:	Trial now transitioned
Date on which this record was first entered in the EudraCT database:	2015-10-28
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

Norway - NOMA

A.2

EudraCT number

2015-002816-34

A.3

Full title of the trial

PErsonalized TREatment of high-risk MAmmary Cancer - the PETREMAC
trial

A.3.1

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

Individualized treatment of locally advanced breast cancer based on
molecular biomarkers - the PETREMAC trial

Persontilpasset behandling av pasienter med lokalavansert brystkreft
basert på molekylære prediktive biomarkører (PETREMAC studien)
- in Norwegian (not Swedish)

A.3.2

Name or abbreviated title of the trial where available

PETREMAC trial

A.4.1

Sponsor's protocol code number

2015/8463

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	Helse Bergen, Haukeland University Hospital
B.1.3.4	Country	Norway
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Western Norway Regional Health Authority
B.4.2	Country	Norway
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Helse Bergen, Haukeland University Hospital
B.5.2	Functional name of contact point	Reseach and development dept
B.5.3	Address:
B.5.3.1	Street Address	Haukelandsveien 22
B.5.3.2	Town/ city	Bergen
B.5.3.3	Post code	5021
B.5.3.4	Country	Norway
B.5.6	E-mail	postmottak@helse-bergen.no

D. IMP Identification
D.IMP: 1
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.2.1.1.1	Trade name	Ibrance
D.2.1.1.2	Name of the Marketing Authorisation holder	Pfizer
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	palbociclib
D.3.2	Product code	PD0332991
D.3.4	Pharmaceutical form	Tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
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	Perjeta
D.2.1.1.2	Name of the Marketing Authorisation holder	Roche
D.2.1.2	Country which granted the Marketing Authorisation	Norway
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	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.3.11 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	No
D.IMP: 3
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	Olaparib-Lynparza
D.2.1.1.2	Name of the Marketing Authorisation holder	Astra Zeneca
D.2.1.2	Country which granted the Marketing Authorisation	Norway
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
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
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

Locally advanced breast cancer

E.1.1.1

Medical condition in easily understood language

Breast cancer with large tumors

E.1.1.2

Therapeutic area

Diseases [C] - Cancer [C04]

MedDRA Classification

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

Identify molecular markers of therapy response/resistance and survival
outcome in patients with locally advanced breast cancer

E.2.2

Secondary objectives of the trial

a) To assess changes in genetic/epigenetic disturbances in tumor tissue during therapy
b) The objective response rate (ORR) of personalized medicine, compared to ORR for best standard-of-care using historical data for comparison.
c) Tumor Ki67 reduction after 2 and 5 weeks of treatment in Arm A.
d) To estimate recurrence-free and overall survival when patients are treated with the optimal personalized treatment available as of 2015, using historical data for comparison.
e) To evaluate the percentage of patients completing neoadjuvant treatment as outlined in Figure 1 and completing surgery.
f) Breast conserving surgery rate (potential to avoid mastectomy).
g) To assess the safety and tolerability of the study treatment given.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Previously untreated, histologically confirmed non-inflammatory
breast cancer, >4 cm in diameter and /or metastatic ipsilateral axillary
deposits for which the smallest diameter of the largest node >2 cm by CT
or ultrasound scan.
 WHO performance status 0-1
 Known tumor ER, PGR, HER2 and TP53 status.
 Known tumor Ki67 percentage (if ER/PGR>50% and TP53 wt status).
 Distant metastasis not suspected. Patients will undergo radiology
exams during screening phase, after signing the informed consent.
 Age >18 years
 Patients must have clinically and/or radiographically documented
measurable breast cancer according to RECIST.
 Radiology studies (CT thorax/abdomen and bone scintigraphy/bone
scan) must be performed within 28 days prior to registration.
 Absence of any psychological, familial, sociological or geographical
condition potentially hampering compliance with the study protocol and
follow-up schedule; those conditions should be discussed with the
patient before registration in the trial
 Before patient registration/randomization, written informed consent
must be given according to national and local regulations.
 For arms B-H:
 Neutrophils > 1.5 x 109/L
 Platelets > 100 x 109/L
 Bilirubin < 2 x upper limit normal (ULN). For patients with Gilbert´s
syndrome bilirubin >2 x ULN is accepted if there is no evidence of biliary
obstruction.
 Serum creatinine < 1.5 x ULN
 ALT and Alk Phos (ALP) <2.5 x ULN
 INR < 1.5

E.4

Principal exclusion criteria

Unstable angina pectoris or heart failure
 Pregnant or lactating patients can not be included.
 Clinical evidence of serious coagulopathy. Prior arterial/venous
thrombosis or embolism does not exclude patients from inclusion, unless
patient is considered unfit by study oncologist.
 Patient not able to give an informed consent or comply with study
regulations as deemed by study investigator

E.5 End points

E.5.1

Primary end point(s)

The primary endpoint of this trial is to prospectively evaluate the predictive and prognostic value of pre-treatment assessment of a panel of 300 known potential driver mutations in breast cancer by next generation sequencing of tumor DNA.

E.5.1.1

Timepoint(s) of evaluation of this end point

Annualy

E.5.2

Secondary end point(s)

The secondary endpoints of this trial are;
a) To assess changes in genetic/epigenetic disturbances in tumor tissue during therapy
b) The objective response rate (ORR) of personalized medicine, compared to ORR for best standard-of-care using historical data for comparison.
c) Tumor Ki67 reduction after 2 and 5 weeks of treatment in Arm A.
d) To estimate recurrence-free and overall survival when patients are treated with the optimal personalized treatment available as of 2015, using historical data for comparison.
e) To evaluate the percentage of patients completing neoadjuvant treatment as outlined in Figure 1 and completing surgery.
f) Breast conserving surgery rate (potential to avoid mastectomy).
g) To assess the safety and tolerability of the study treatment given.

E.5.2.1

Timepoint(s) of evaluation of this end point

Side effects: continously.
Efficacy of treatment: interim analysis after first 100 patients, estimated to be after 2 yrs

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

Yes

E.6.13.1

Other scope of the trial description

Identify predictive markers of response to neoadjuvant treatment.

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

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

Yes

E.8.1.7.1

Other trial design description

Single arm, open label

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

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

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 trial is 10 years after the inclusion of last subject on trial.

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

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)

F.1.2.1

Number of subjects for this age range:

150

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

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 2015-10-28.

Yes

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

200

F.4.2

For a multinational trial

F.4.2.1

In the EEA

200

F.4.2.2

In the whole clinical trial

200

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 finishing neoadjuvant therapy on trial, with a curative intent, patients will be operated and receive adjuvant radiotherapy and/or endocrine therapy and/or adjuvant chemotherapy and thereafter observation for 10 years for survival monitoring.

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

2016-02-09

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2015-10-05

P. End of Trial
P.	End of Trial Status	Trial now transitioned

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