A clinical study comparing Acelarin with gemcitabine in patients with metastatic pancreatic carcinoma

ISRCTN	ISRCTN16765355
DOI	https://doi.org/10.1186/ISRCTN16765355
EudraCT/CTIS number	2014-004653-14
ClinicalTrials.gov number	NCT03610100
Secondary identifying numbers	19200

Submission date: 22/07/2015
Registration date: 23/07/2015
Last edited: 19/07/2022

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Cancer

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Record updated in last year

Plain English Summary

http://www.cancerresearchuk.org/about-cancer/find-a-clinical-trial/a-trial-looking-at-acelarin-and-gemcitabine-for-pancreatic-cancer-that-has-spread-acelarate

Contact information

Miss Kellie Platt
Scientific

Liverpool Clinical Trials Centre
University of Liverpool
Block C, Waterhouse Building
1-5 Brownlow St
Liverpool
L69 3GL
United Kingdom

Phone	+44 (0)151 794 8897
Email	Kellie.Platt@liverpool.ac.uk

Study information

Study design	Randomised; Interventional; Design type: Treatment
Primary study design	Interventional
Secondary study design	Randomised controlled trial
Study setting(s)	Hospital
Study type	Treatment
Participant information sheet	Not available in web format, please use contact details to request a participant information sheet
Scientific title	A phase III, open label, multicentre randomised clinical study comparing Acelarin (NUC1031) with gemcitabine in patient with metastatic pancreatic carcinoma (ACELARATE)
Study acronym	ACELARATE
Study hypothesis	To evaluate the efficacy and safety of Acelarin compared with gemcitabine in patients with metastatic pancreatic carcinoma. Exploratory objectives are to discover possible biomarkers to predict additional benefit of Acelarin over gemcitabine for subsequent validation.
Ethics approval(s)	NRES Committee East Midlands - Nottingham 2, 07/04/2015, ref: 15/EM/0095
Condition	Metastatic pancreatic carcinoma
Intervention	Arm 1: Acelarin: 825 mg/m2 administered intravenously on days 1, 8 and 15 of a 28 day cycle. Arm 2: Gemcitabine 1000mg/m2 administered intravenously on days 1, 8 and 15 of a 28 day cycle. Randomisation will be stratified by ECOG performance status (PS) (0/1 vs 2). The planned treatment duration per patient will be until progression of disease, unacceptable toxicity or withdrawal of consent. Participation in the study will be until withdrawal of consent or death. Patients who stop treatment before having developed progressive disease (PD) will be assessed every 12 weeks for response until PD occurs. Patients will receive screening CT scan and ECG. CT scan every 12 weeks after screening until PD as per RECIST 1.1. Optional additional biopsy for translational biomarker analysis. Optional translational blood sample taken at baseline, day 1 of each cycle and end of treatment. Added 20/07/2018: Sub-study Eight of the existing sites are running the peripheral infusion sub-study. This is open to 30 patients who have been randomised onto Arm A: Acelarin first. The purpose of the sub-study is to explore whether a peripheral infusion of Acelarin (NUC-1031) through a vein in the back of the hand or arm is well-tolerated. The bag of Acelarin has 500ml of saline, rather than 250ml for the main study. The sub-study’s purpose is to explore if any sub-study patients encounter any injection site reactions. In the sub-study CTCAE grade 2 pain is split into two levels: Grade 2A for pain only, with no associated phlebitis, lipdostrophy or oedema Grade 2B for pain with associated phlebitis, lipdostrophy or oedema Patients are reviewed for any injection site reactions during the infusion and again one hour after the infusion has completed. Patients who are participating in the sub-study will sign the supplemental appendix to the Patient Information Sheet as well after signing the main study consent form.
Intervention type	Drug
Pharmaceutical study type(s)
Phase	Phase III
Drug / device / biological / vaccine name(s)	Acelarin, gemcitabine
Primary outcome measure	Overall survival; Timepoint(s): Date of randomisation to date of death.
Secondary outcome measures	1. Discover possible biomarkers to predict additional benefit of Acelarin over gemcitabine alone; Timepoint(s): For subsequent validation in larger scale studies 2. Progression Free Survival; Timepoint(s): Date of randomisation to the earlier of date of progressive disease, date of death or censoring date 3. Quality of life; Timepoint(s): Assessed using the EORTC QLQ-C30 v3 and EORTC QLQ-PAN26 throughout the study and 3 monthly follow up 4. Radiological response and disease control rate; Timepoint(s): Objective radiological response is defined as occurrence of complete (CR) or partial responders (PR) 5. Safety; Timepoint(s): Occurrence of SAE or grade 3+ toxicity measured until 30 days after last study treatment
Overall study start date	09/09/2014
Overall study end date	31/12/2020

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	Both
Target number of participants	Planned Sample Size: 328; UK Sample Size: 328; Description: From our own data for recruitment to advanced pancreatic cancer trials (VIP and Telovac), we can estimate that this would require 328 patients in total yielding 270 deaths - assuming that 4 sites opened/month to a total of 40 sites with mean recruitment rate 0.39 pts/site/month, and 36 month study duration inclusive of 10 month minimum follow-up (excluding time for set-up and closedown).
Participant inclusion criteria	1. Aged at least 18 years 2. Histologically or cytologically proven pancreatic ductal adenocarcinoma or undifferentiated carcinoma of the pancreas* 3. 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 4. Contrast enhanced computerised tomography (CT) scan of the thorax, abdomen and pelvis within 28 days prior to commencing treatment 5. Unidimensionally measurable disease 6. ECOG performance status 0, 1 or 2 where treatment with combination chemotherapy is not deemed appropriate or is declined by the patient 7. Platelets =100 x 109/l; neutrophils = 1.5 x 109/l at entry 8. Documented life expectancy > 3 months 9. 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
Participant exclusion criteria	1. Laboratory results: 1.1. Serum bilirubin = 1.5x the upper limit of reference range (ULRR) 1.2. Haemoglobin < 10G/dl 1.3. Creatinine clearance < 30 mL/minute (calculated by CockcroftGault formula) 1.4. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) or alkaline phosphatase (ALP) >2.5 x ULN or > 5x ULN if judged by the investigator to be related to liver metastases. 2. Medical or psychiatric conditions compromising informed consent. 3. Intracerebral metastases or meningeal carcinomatosis. 4. 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. 5. Pregnancy or breast feeding. 6. 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. 7. Radiotherapy within the last 4 weeks prior to start of study treatment. 8. 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. 9. Hypersensitivity to gemcitabine or any of the excipients of gemcitabine or Acelarin (NUC1031). 10. 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 condom (1) or abstaining from sexual intercourse, until six months after treatment has ended: 10.1. Combined (oestrogen and progesterone containing) hormonal contraception associated with inhibition of ovulation: either oral, intravaginal or transdermal. 10.2. Progesterone-only hormonal contraception associated with inhibition of ovulation: either oral, injectable or implantable. 10.3. Intrauterine device (IUD) 10.4. Intrauterine hormonereleasing system (IUS) 10.5. Bilateral tubal occlusion 10.6. Vasectomised partner (2) 10.7. Sexual abstinence (3) (1) Male 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.
Recruitment start date	17/08/2015
Recruitment end date	31/12/2019

Locations

Countries of recruitment

England
United Kingdom

Study participating centre

Liverpool Cancer Trials Unit

Cancer Research UK
University of Liverpool
1st floor Block C, Waterhouse Building
3 Brownlow Street
Liverpool
L69 3GL
United Kingdom

Sponsor information

Clatterbridge Centre for Oncology NHS Trust
Hospital/treatment centre

Clatterbridge Hospital
Clatterbridge Road
Wirral
CH63 4JY
England
United Kingdom

"ROR"	https://ror.org/05gcq4j10

Funders

Funder type

Industry

NuCana BioMed Ltd

No information available

Results and Publications

Intention to publish date	31/10/2022
Individual participant data (IPD) Intention to share	Yes
IPD sharing plan summary	Available on request
Publication and dissemination plan	The trialists intend to publish the study results with regard to the primary and secondary endpoints upon completion of the study. The abstract will be discussed at meetings and will be in peer reviewed papers.
IPD sharing plan	The datasets generated during and/or analysed during the current study are/will be available upon request from the Trial Statistician Dr Richard Jackson (richj23@liverpool.ac.uk).

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
HRA research summary			28/06/2023	No	No

Editorial Notes

19/07/2022: The intention to publish date has been changed from 31/12/2021 to 31/10/2022.
08/07/2022: The public contact has been removed and a scientific contact added.
19/07/2019: ClinicalTrials.gov number added.
03/04/2019: The condition has been changed from "Topic: Cancer; Subtopic: Upper Gastro-Intestinal Cancer; Disease: Pancreas" to "Metastatic pancreatic carcinoma" following a request from the NIHR.
23/07/2018: IPD sharing statement added.
20/07/2018: The following changes were made to the trial record:
1. The recruitment end date was changed from 31/05/2018 to 31/12/2019.
2. The overall trial end date was changed from 31/12/2018 to 31/12/2020.
3. The intention to publish date was added.
4. The interventions were updated.
02/02/2016: Plain English summary link added.