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Acelarin First Line Randomised Pancreatic Study (ACELARATE)

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ClinicalTrials.gov Identifier: NCT03610100
Recruitment Status : Recruiting
First Posted : August 1, 2018
Last Update Posted : August 1, 2018
Sponsor:
Collaborators:
Cancer Research UK
University of Liverpool
Information provided by (Responsible Party):
The Clatterbridge Cancer Centre NHS Foundation Trust

Brief Summary:

The primary purpose of this study is to assess whether Acelarin (NUC-1031) is superior to gemcitabine in terms of overall survival for treatment of patients with metastatic pancreatic carcinoma. In addition disease progression, quality of life and comparative safety will be evaluated. Secondary objectives are to compare between the two treatment groups the following:

  • Progression Free Survival (PFS)
  • Radiological Response and disease control rate
  • Toxicity and safety
  • Quality of Life

Additional, exploratory objectives are to discover and validate possible biomarkers to predict additional benefit of Acelarin (NUC-1031) over gemcitabine alone.


Condition or disease Intervention/treatment Phase
Pancreatic Acinar Carcinoma Pancreatic Neoplasms Drug: Acelarin Drug: Gemcitabine Phase 2 Phase 3

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 328 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase III, Open Label, Multicentre Randomised Clinical Study Comparing Acelarin (NUC-1031) With Gemcitabine in Patients With Metastatic Pancreatic Carcinoma
Study Start Date : December 2015
Estimated Primary Completion Date : September 2019
Estimated Study Completion Date : December 2019


Arm Intervention/treatment
Experimental: Acelarin (NUC-1031)

825 mg/m2 administered intravenously over 15 to 30 minutes on days 1, 8 and 15 of a 28 day cycle.

Patients will be seen on a weekly basis during the time they are on active treatment and will be treated until disease progression.

Drug: Acelarin
825 mg/m2 administered intravenously over 15 to 30 minutes on days 1, 8 and 15 of a 28 day cycle. Number of Cycles: until disease progression or unacceptable toxicity develops.
Other Name: NUC-1031

Active Comparator: Gemcitabine

Gemcitabine: 1000mg/m2 administered intravenously as a 30 minute infusion on days 1, 8 and 15 of a 28 day cycle.

Patients will be seen on a weekly basis during the time they are on active treatment and will be treated until disease progression.

Drug: Gemcitabine
1000 mg/m2 administered intravenously as a 30 minute infusion on days 1, 8 and 15 of a 28 day cycle. Number of Cycles: until disease progression or unacceptable toxicity develops.
Other Name: Gemzar




Primary Outcome Measures :
  1. Number of participants that have survived throughout treatment and also into follow-up, as measured by the primary cause of death and date of death CRFs. [ Time Frame: 4 years ]

Secondary Outcome Measures :
  1. Number of participants that survive progression-free and for how long, as assessed by 12-weekly CT scan assessments per RECIST v1.1 and end of study CRF to capture the reasons for coming off study. [ Time Frame: 4 years ]
  2. Number of participants that show an objective response, as demonstrated by 12-weekly CT scan assessments per RECIST v1.1. [ Time Frame: 4 years ]
  3. Number of participants deemed to have disease control, as demonstrated by 12-weekly CT scan assessments per RECIST v1.1. [ Time Frame: 4 years ]
  4. Number of patients with treatment-related adverse events as assessed by CTCAE v4.03. Toxicity is assessed by CTCAE v4.03 alongside Quality of Life Questionnaires, QLQ-C30 and QLQ-PAN26. [ Time Frame: 4 years ]

Other Outcome Measures:
  1. Discovery of possible biomarkers which may predict any additional benefit of Acelarin over gemcitabine. These will be assessed from plasma, cell pellet and serum samples collected from participants throughout the trial. [ Time Frame: 4 years ]
    To validate candidate predictive biomarkers, baseline patient samples will be analysed by Luminex technology. Paraffin embedded formalin fixed pancreatic cancer biopsy tissue samples will be used for analysis of candidate predictive biomarkers. Transcripts that will be assayed with RNAScope and scored for staining are: hENT1; CDA, dCK; RRM1 & RRM2. RNAscope will be used to detect mRNA expression by using a site directed probe, to a particular sequence in the gene of interest, which is then amplified and stained. This enables quantification of the mRNA expression and allows subsequent survival analysis.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age ≥ 18 years.
  • Histologically or cytologically proven pancreatic ductal adenocarcinoma or undifferentiated carcinoma of the pancreas.
  • 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.
  • Contrast enhanced computerised tomography (CT) scan of the thorax, abdomen and pelvis within 28 days prior to commencing treatment.
  • Unidimensionally measurable disease.
  • ECOG performance status 0, 1 or 2 where combination chemotherapy is not deemed appropriate or is declined by the patient.
  • Platelets ≥100 x 109/l; WBC ≥ 3 x 109/l; neutrophils ≥ 1.5 x 109/l at entry.
  • Documented life expectancy > 3 months.
  • Informed written consent.

Exclusion Criteria:

  • 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.
  • Medical or psychiatric conditions compromising informed consent.
  • Intracerebral metastases or meningeal carcinomatosis.
  • 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 study or which would jeopardize compliance with the protocol.
  • Pregnancy or breast feeding.
  • 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.
  • Radiotherapy within the last 4 weeks prior to start of study treatment.
  • 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.
  • Hypersensitivity to gemcitabine or any of the excipients of gemcitabine or Acelarin (NUC-1031).
  • 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* or abstaining from sexual intercourse, until six months after treatment has ended:

    • Combined (oestrogen and progesterone containing) hormonal contraception associated with inhibition of ovulation: either oral, intravaginal or transdermal.
    • Progesterone-only hormonal contraception associated with inhibition of ovulation: either oral, injectable or implantable.
    • Intra-uterine device (IUD)
    • Intra-uterine hormone-releasing system (IUS)
    • Bilateral tubal occlusion
    • Vasectomised partner *Male or female condom with or without spermicide is not an acceptable method of contraception alone.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03610100


Contacts
Contact: Rachael E Baxter 44 151 794 8284 rbaxter@liverpool.ac.uk
Contact: Charlotte Rawcliffe 44 151 794 8167 C.Rawcliffe@liverpool.ac.uk

Locations
United Kingdom
Cancer Research UK Liverpool Cancer Trials Unit Recruiting
Liverpool, Merseyside, United Kingdom, L69 3GL
Contact: Rachael E Baxter    44 151 794 8284    rbaxter@liverpool.ac.uk   
Sponsors and Collaborators
The Clatterbridge Cancer Centre NHS Foundation Trust
Cancer Research UK
University of Liverpool
Investigators
Principal Investigator: Daniel H Palmer, BSC, PhD University of Liverpool

Publications:
Von Hoff DD, Ervin TJ, Arena FP, et al: "Randomized phase III study of weekly nab-paclitaxel plus gemcitabine versus gemcitabine alone in patients with metastatic adenocarcinoma of the pancreas (MPACT)". 2013 Gastrointestinal Cancers Symposium. J Clin Oncol 31, 2013 (suppl 4; abstract: LBA148)
Ghazaly, E.A. et al. "ProGem1: Phase I first-in-human study of the novel nucleotide NUC-1031 in adult patients with advanced solid tumors" J Clin Oncol 31, 2013 (suppl; abstr 2576)
Ghazaly, E.A. et al. "ProGem1: A phase I/II study of a first-in-class nucleotide, Acelarin, in patients with advanced solid tumors" J Clin Oncol 32:5s, 2014 (suppl; abstr 2531)

Responsible Party: The Clatterbridge Cancer Centre NHS Foundation Trust
ClinicalTrials.gov Identifier: NCT03610100     History of Changes
Other Study ID Numbers: ISRCTN16765355
First Posted: August 1, 2018    Key Record Dates
Last Update Posted: August 1, 2018
Last Verified: July 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Keywords provided by The Clatterbridge Cancer Centre NHS Foundation Trust:
Pancreatic
Neoplasms
Metastatic
Gemcitabine
Gemzar
Phosphoramidate
Cytidine Aminohydrolase
Deoxycytidine Kinase
Nucleoside Transport Proteins
hENT1 protein, human

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Acinar Cell
Pancreatic Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Adenocarcinoma
Gemcitabine
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs