Clinical Trials Register

Summary
EudraCT Number:	2014-004653-14
Sponsor's Protocol Code Number:	UoL000097
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:	2015-02-25
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

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

UK - MHRA

A.2

EudraCT number

2014-004653-14

A.3

Full title of the trial

A Phase III, open label, multicentre randomised clinical study comparing Acelarin (NUC-1031) with Gemcitabine in patient with metastatic pancreatic carcinoma.
(ACELARATE)

A.3.1

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

A Phase III, open label, multicentre randomised clinical study comparing Acelarin (NUC-1031) with Gemcitabine in patients with metastatic pancreatic carcinoma.

A.3.2

Name or abbreviated title of the trial where available

ACELARATE

A.4.1

Sponsor's protocol code number

UoL000097

A.5.1

ISRCTN (International Standard Randomised Controlled Trial) Number

ISRCTN16765355

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	The Clatterbridge Cancer Centre NHS Foundation Trust
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	NuCana plc
B.4.2	Country	United Kingdom
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	The Clatterbridge Cancer Centre NHS Foundation Trust
B.5.2	Functional name of contact point	Dr Maria Maguire
B.5.3	Address:
B.5.3.1	Street Address	Clatterbridge Road
B.5.3.2	Town/ city	Bebington
B.5.3.3	Post code	CH63 4JY
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	441515565321
B.5.6	E-mail	maria.maguire2@nhs.net

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.2.1.2	Country which granted the Marketing Authorisation	United Kingdom
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	N/A
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	95058814
D.3.9.4	EV Substance Code	AS1
D.3.10	Strength
D.3.10.1	Concentration unit	mg/g milligram(s)/gram
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	200
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	Gemcitabine (INN) is a pyrimidine analogue.
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	Acelarin
D.3.2	Product code	NUC-1031
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	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/l milligram(s)/litre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	113
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

Metastatic pancreatic carcinoma.

E.1.1.1

Medical condition in easily understood language

Pancreatic carcinoma that has spread to other areas in the body as well as the originating site.

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

To assess whether Acelarin is superior to Gemcitabine in terms of overall survival for treatment of patients with metastatic pancreatic carcinoma.

E.2.2

Secondary objectives of the trial

To compare between the two treatment groups:-
- Progression Free Survival (PFS)
- Radiological Response and disease control rate
- Toxicity and safety
- Quality of Life

Exploratory objectives

To discover possible biomarkers to predict additional benefit of Acelarin over gemcitabine alone for subsequent validation in larger scale studies. Pharmacokinetic analysis will be performed to establish patient to patient variation for both IMPs.

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

Acelarate Study – Peripheral Sub-Study Addendum
Version 1.0, 10-Oct-2016.

This sub-study is designed to explore whether the saline based formulation of Acelarin can be administered by peripheral IV infusion with a manageable amount of local injection site reactions.

This is considered to be important as the majority of patients receiving gemcitabine in the standard of care clinical setting, choose to receive treatment by peripheral intravenous (IV) infusion as an alternative to having a Central Venous Access Device (CVAD) implanted. Therefore it is important to assess the tolerability of Acelarin in this same setting.

The sub-study addendum and supporting documents will only be available to those centres participating in the sub-study. A supplementary greenlight approval process will also be put in place prior to enrolment of sub-study patients.

The sub-study will follow the same schedule as the main ACELARATE study. The only difference that the sub-study addendum will introduce is that Acelarin will be administered via peripheral IV infusion, as opposed to being administered through a central line, as occurs in the main study.

The sub-study will examine whether any local site reactions occur, and if they occur whether they are associated with pain only or pain with associated oedema, lipodystrophy or phlebitis.

For full details please review the following document which is attached to this application:- Acelarate Study – Peripheral Sub-Study Addendum - Version 1.0 dated 10 October 2016.

E.3

Principal inclusion criteria

a) Age ≥ 18 years.
b) Histologically or cytologically proven pancreatic ductal adenocarcinoma or undifferentiated carcinoma of the pancreas.*
c) Metastatic disease precluding curative surgical resection or definitive locally directed therapies such as chemo radiation. Patients who have relapsed following previously resected pancreatic cancer can be included.
d) Contrast enhanced computerised tomography (CT) scan of the thorax, abdomen and pelvis within 28 days prior to commencing treatment
e) Unidimensionally measurable disease.
f) ECOG performance status 0, 1 or 2 where treatment with combination chemotherapy is not deemed appropriate or is declined by the patient.
g) Platelets ≥100 x 109/l; neutrophils ≥ 1.5 x 109/l at entry.
h) Documented life expectancy > 3 months.
i) Informed written consent.

*Patients will be approached for consenting to provide either an additional core of tissue material for biomarker discovery at the same time as a diagnostic biopsy or in those patients that have already had a diagnostic biopsy to undergo a second biopsy after randomisation into the trial. Neither of these biopsies is compulsory. Patients who don't wish to have extra tissue taken for Biomarker discovery will be approached for consent to released surplus tissue from the original diagnostic specimen if this exists.

E.4

Principal exclusion criteria

a) Laboratory results:
• Serum bilirubin ≥ 1.5x the upper limit of reference range (ULRR).
• Haemoglobin < 10G/dl
• Creatinine clearance < 30 mL/minute (calculated by Cockcroft-Gault formula)
• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >2.5 x ULN or > 5x ULN if judged by the investigator to be related to liver metastases.
b) Medical or psychiatric conditions compromising informed consent.
c) Intracerebral metastases or meningeal carcinomatosis.
d) Evidence of severe or uncontrolled systemic disease or any concurrent condition which in the Investigator’s opinion makes it undesirable for the patient to participate in the trial or which would jeopardize compliance with the protocol.
e) Pregnancy or breast feeding.
f) Previous chemotherapy for locally advanced and metastatic disease. Adjuvant chemotherapy for resected pancreatic cancer will be permitted provided that chemotherapy was completed > 12 months previously.
g) Radiotherapy within the last 4 weeks prior to start of study treatment.
h) Concurrent malignancies or invasive cancers diagnosed within past 5 years except for adequately treated basal cell carcinoma of the skin, in situ carcinoma of the uterine cervix or resected pancreatic cancer.
i) Hypersensitivity to gemcitabine or any of the excipients of gemcitabine or Acelarin (NUC-1031).
j) j) All men or women of reproductive potential, unless using at least two contraceptive precautions, one of which must be from the list below, the other must be a condom1 or abstaining from sexual intercourse, until six months after treatment has ended:
o Combined (oestrogen and progesterone containing) hormonal contraception associated with inhibition of ovulation: either oral, intravaginal or transdermal.
o Progesterone-only hormonal contraception associated with inhibition of ovulation: either oral, injectable or implantable.
o Intra-uterine device (IUD)
o Intra-uterine hormone-releasing system (IUS)
o Bilateral tubal occlusion
o Vasectomised partner2
o Sexual abstinence3

1Male or female condom with or without spermicide is not an acceptable method of contraception alone.
2 Vasectomised partner is a highly effective birth control method provided that partner is the sole sexual partner of the woman of childbearing potential trial participant and that the vasectomised partner has received medical assessment of the surgical success.
3 In the context of this guidance sexual abstinence is considered a highly effective method only if defined as refraining from heterosexual intercourse during the entire period of risk associated with the study treatments. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the subject.

E.5 End points

E.5.1

Primary end point(s)

Overall survival (OS) time.

E.5.1.1

Timepoint(s) of evaluation of this end point

When either the target number of events has occurred or 10 months after the last of all patients have been randomised, whichever is earlier.

E.5.2

Secondary end point(s)

1. Progression free survival
2. Radiological response and disease control
3. Quality of life (assessed using the EORTC QLQ-C30 v3 and EORTC QLQ-PAN-26)
4. Safety (occurrence of SAE or grade 3+ toxicity)

E.5.2.1

Timepoint(s) of evaluation of this end point

When either the target number of events for the primary endpoint of survival has occurred or 10 months after the last of all patients have been randomised, whichever is earlier.

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

E.6.12

Pharmacoeconomic

Yes

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)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

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)

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

United States

E.8.7

Trial has a data monitoring committee

Yes

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 the trial is defined to be the date on which data for all participants is frozen and data entry privileges are withdrawn from the trial database. The trial may be closed prematurely by the Trial Steering Committee (TSC), on the recommendation of the Independent Data and Safety Monitoring Committee (IDSMC).

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:

218

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

110

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

F.3.3.2

Women of child-bearing potential using contraception

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

328

F.4.2

For a multinational trial

F.4.2.1

In the EEA

328

F.4.2.2

In the whole clinical trial

328

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)

End of treatment visit with haematology and ECG then a 3 month follow up with quality of life assessment. Treatment as per local standard of care treatment for this cohort of patients otherwise.

G. Investigator Networks to be involved in the Trial
G.4 Investigator Network to be involved in the Trial: 1

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2015-04-17

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2015-04-07

P. End of Trial
P.	End of Trial Status	GB - no longer in EU/EEA

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