Clinical Trials Register

Summary
EudraCT Number:	2016-004156-29
Sponsor's Protocol Code Number:	PRIMUS0022016
National Competent Authority:	UK - MHRA
Clinical Trial Type:	EEA CTA
Trial Status:	GB - no longer in EU/EEA
Date on which this record was first entered in the EudraCT database:	2018-05-21
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

UK - MHRA

A.2

EudraCT number

2016-004156-29

A.3

Full title of the trial

PRIMUS 002: An umbrella phase II study examining two neo-adjuvant regimens (FOLFOX-A and AG) in resectable and borderline resectable Pancreatic Ductal Carcinoma (PDAC), focusing on biomarker and liquid biopsy development

A.3.1

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

A trial looking at two chemotherapy treatments given prior to surgery for pancreatic cancer, looking at biomarker development

A.3.2

Name or abbreviated title of the trial where available

PRIMUS 002

A.4.1

Sponsor's protocol code number

PRIMUS0022016

A.5.1

ISRCTN (International Standard Randomised Controlled Trial) Number

ISRCTN34129115

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	NHS Greater Glasgow and Clyde
B.1.3.4	Country	United Kingdom
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
B.4.2	Country
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	CRUK CTU Glasgow
B.5.2	Functional name of contact point	Judith Dixon-Hughes
B.5.3	Address:
B.5.3.1	Street Address	Level 0, Beatson WoSCC
B.5.3.2	Town/ city	1053 Great Western Road, Glasgow
B.5.3.3	Post code	G12 0YN
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	01413017540
B.5.6	E-mail	judith.dixon@glasgow.ac.uk

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	Abraxane
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.3.1	Product name	Abraxane
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	Paclitaxel Albumin Bound
D.3.9.1	CAS number	33069-62-4
D.3.9.3	Other descriptive name	nab-Paclitaxel
D.3.9.4	EV Substance Code	AS1
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 stabilizing agent. It is derived from human blood subject to approved donor screening and product manufacturing processes
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	Information not present in EudraCT
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.3.4	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	AS2
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	38
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	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	Information not present in EudraCT
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	Oxaliplatin
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.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Oxaliplatin
D.3.9.1	CAS number	61825-94-3
D.3.9.4	EV Substance Code	AS3
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	No
D.IMP: 4
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	Information not present in EudraCT
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	Fluorouracil
D.3.4	Pharmaceutical form	Solution for injection/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	Fluorouracil
D.3.9.1	CAS number	51-21-8
D.3.9.3	Other descriptive name	5FU
D.3.9.4	EV Substance Code	AS4
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	25
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Fluorouracil
D.3.9.1	CAS number	51-21-8
D.3.9.3	Other descriptive name	5FU
D.3.9.4	EV Substance Code	AS5
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	50
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: 5
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	Information not present in EudraCT
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	Folinic acid
D.3.4	Pharmaceutical form	Solution for injection/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	Folinic acid (calcium salt)
D.3.9.1	CAS number	1492-18-8
D.3.9.3	Other descriptive name	Calcium Folinate
D.3.9.4	EV Substance Code	AS8
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	3
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Folinic acid (calcium salt)
D.3.9.1	CAS number	1492-18-8
D.3.9.3	Other descriptive name	Calcium Folinate
D.3.9.4	EV Substance Code	AS9
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	7.5
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Folinic acid (calcium salt)
D.3.9.1	CAS number	1492-18-8
D.3.9.3	Other descriptive name	Calcium Folinate
D.3.9.4	EV Substance Code	AS10
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	10
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Folinic acid (sodium salt)
D.3.9.1	CAS number	163254-40-8
D.3.9.3	Other descriptive name	Disodium Folinate
D.3.9.4	EV Substance Code	AS11
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	50
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Levofolinic acid (sodium salt)
D.3.9.1	CAS number	42476-21-1
D.3.9.3	Other descriptive name	disodium levofolinate
D.3.9.4	EV Substance Code	AS12
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	50
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Levofolinic acid (calcium salt)
D.3.9.1	CAS number	80433-71-2
D.3.9.3	Other descriptive name	calcium levofolinate
D.3.9.4	EV Substance Code	AS13
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	10
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: 6
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	Information not present in EudraCT
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.3.4	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.3.8 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	AS14
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	38
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	AS15
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	40
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	AS16
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	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: 7
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	Information not present in EudraCT
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	Capecitabine
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	Capecitabine
D.3.9.1	CAS number	154361-50-9
D.3.9.4	EV Substance Code	AS17
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	150
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Capecitabine
D.3.9.1	CAS number	154361-50-9
D.3.9.4	EV Substance Code	AS18
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	500
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Capecitabine
D.3.9.1	CAS number	154361-50-9
D.3.9.4	EV Substance Code	AS19
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	300
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
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

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	20.0
E.1.2	Level	LLT
E.1.2	Classification code	10033608
E.1.2	Term	Pancreatic cancer resectable
E.1.2	System Organ Class	100000004864

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

The primary study end-point is progression post FOLFOX-A induction treatment as defined by RECIST 1.1 The association of this with a proposed biomarker of treatment responsiveness will be examined.

The primary translational objective of PRIMUS 002 is to assess efficacy of proposed biomarker(s) in predicting disease progression (treatment failure) rates in FOLFOX-A.

E.2.2

Secondary objectives of the trial

1. Translational research assessment of (1) clonal evolution and acquired resistance mechanisms due to treatment, (2) feasibility and accuracy of liquid biopsies
2. Response based on RECIST 1.1 post neo-adjuvant chemotherapy
3. CAP tumour regression grade post surgery
4. R0 rate post surgery
5. Overall survival
6. Disease free survival
7. Safety and tolerability of study drugs as assessed by NCI CTCAE 4.03
8. Safety and tolerability of CRT as assessed by NCI CTCAE 4.03
9. Rate of surgical complicatons as assessed by NCI CTCAE 4.03
10. Neurotoxicity as assessed by GOG NTX4
11. QoL as assessed by EORTC QLQ-C30 version 3 and the pancreatic-specific QLQ-PAN26 QOL module
12. Health economics as assessed by EQ-5D-5L and resource use

There are also some exploratory endpoints
• Exploratory analysis to define biomarkers of therapeutic responsiveness of AG, by comparing the AG responders to non-responders.

The below exploratory endpoints relate to the PET sub-study only
• Do patients with at

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

There is a sub study regarding PET scanning. Approximately 100 patients from the Beatson West of Scotland Cancer Centre will be approached to take part in this sub-study via a PET sub-study specific consent. The patients will be asked to undergo a PET scan at baseline and one pre surgery. For the patients proceeding to chemo-radiotherapy a third PET scan will take place prior to chemo-radiotherapy begining

E.3

Principal inclusion criteria

1 Patient has been enrolled in the Precision-Panc Master Protocol and their tissue
has been deemed suitable for NGS analysis (a Precision-Panc Master Protocol
identifier will be required at the time of study enrolment)
2 Signed informed consent given for PRIMUS 002 study
3 Age ≥ 16 years
4 Resectable or borderline resectable pancreatic cancer as defined by NCCN criteria
following discussion at the Multi Disciplinary Team (MDT)
5 Measurable Disease as per RECIST 1.1
6 Histological or cytologically proven pancreatic ductal adenocarcinoma (including
variants)
7 Able to undergo biliary drainage using a covered or partially covered
self-expanding metal stent if jaundiced
8 ECOG performance status 0 and 1
9 Adequate liver/bone marrow function as defined by:
a. Neutrophils (ANC) ≥ 1.5 x 109/l
b. Platelets ≥ 100 x 109/l
c. Haemoglobin ≥ 9.0g/dL
d. White Blood Cells (WBC) ≥ 3 x 109/l
e. Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN) unless
bilirubin rise is due to Gilbert’s syndrome
f. Aspartate transaminase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x
ULN (or <5 x ULN in the presence of liver metastases)
g. Estimated creatinine clearance ≥ 60 mL/min (as calculated by Cockcroft
and Gault or Wright formula or measured by EDTA clearance)
10 Negative serum Human Chorionic Gonadotropin (HCG) test for females with child
bearing potential. Postmenopausal women must have been amenorrhoeic for at least
12 months to be considered of non-childbearing potential
11 Woman of child bearing potential, and men with female partners of child bearing
potential, must agree to use adequate contraceptive measures (see section 8.1.8.1)
for the duration of the study and for up to 6 months after the completion of study
treatment.
12 Able to comply with protocol requirements and deemed fit for surgical resection,
chemotherapy and CRT

E.4

Principal exclusion criteria

1 Distant metastatic disease
2 History of previous or concurrent malignancy diagnosis (except curatively treated
basal cell carcinoma of skin or carcinoma in situ of cervix)
3 Prior chemotherapy or CRT for pancreatic cancer
4 Known hypersensitivity for any component of any study drug
5 Active infection including Herpes Zoster and chickenpox
6 Uncontrolled congestive heart failure (CHF), or history of myocardial ischemia
(MI), unstable angina, stroke, or transient ischemia within previous 6 months.
7 Serious medical or psychological condition precluding neo-adjuvant treatment and
surgical resection
8 New York Heart Association Classification Grade III or IV
9 Body Mass Index (BMI) >35
10 Liver Cirrhosis (except for Child-Pugh A)
11 CPET results outwith appropriate level for surgical resection. AT < 10 or METS < 5 12 Major surgery within 28 days prior to trial entry
13 Any patients receiving treatment with brivudin, sorivudin and analogues
14 Any patient with severe diarrhoea (defined as ≥grade 3 diarrhoea despite maximum
supportive measures and exclusion of underlying infection)
15 Patients with known malabsorption
16 Patients with known or suspected dihydropyrimidine dehydrogenase (DPD) deficiency.
17 Grade ≥ 2 peripheral neuropathy
18 Administration of any investigational drug within 28 days or 5 half-lives,
whichever is longer, prior to receiving the first dose of trial treatment

E.5 End points

E.5.1

Primary end point(s)

Disease progression (treatment failure) post FOLFOX-A treatment

E.5.1.1

Timepoint(s) of evaluation of this end point

RECIST reported CT scans will take place at baseline, prior to the patient's radiotherapy and prior to the patient's planned surgery.

E.5.2

Secondary end point(s)

E.5.2.1

Timepoint(s) of evaluation of this end point

1 – Assessed by analysis of baseline biopsy (taken under Precision-Panc) and subsequent biopsies and paired blood samples
2 – CT scan prior to post chemo visit
3 & 4 & 9 – Post surgery visit
7 – AEs will be assessed at all chemotherapy visits and all subsequent visits until resolutons
8 – AEs will be assessed daily during CRT and at FUP visits
5 & 6 – patients will be followed up on a 6 monthly basis
10 & 11 – Day 1 of chemo cycles, pre CRT, end of CRT , pre surgery visit and at each FUP visit
12 – Day I of chemo cycles, pre CRT, weekly while receiving CRT, pre surgery visit and at each FUP visit

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

Yes

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

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

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

The end of trial is defined as after the last registered patients is 12 months from the date of registration.

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

Yes

F.1.1