Active Symptom Control Alone or With mFOLFOX Chemotherapy for Locally Advanced/ Metastatic Biliary Tract Cancers (ABC06)

January 26, 2020 updated by: Juan Valle, The Christie NHS Foundation Trust

A Phase III, Randomised, Multicentre Open-label Study of Active Symptom Control (ASC) Alone or ASC With Oxaliplatin/ 5F-U Chemotherapy for Patients With Locally Advanced/ Metastatic Biliary Tract Cancers Previously Treated With Cisplatin/ Gemcitabine Chemotherapy.

The purpose of this study is to determine whether fit patients (with ECOG performance score of 0-1) with advanced biliary tract cancer (ABC) benefit from chemotherapy in the second-line setting (after prior therapy with cisplatin and gemcitabine) in terms of overall survival.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Active chemotherapy drugs for the treatment of ABC include gemcitabine, fluoropyrimidines and platinum agents. The randomized NCRN phase III ABC-02 trial provided level A evidence supporting first-line combination cisplatin and gemcitabine (CisGem) chemotherapy in ABC. To date, there is no randomized data to support the use of second-line chemotherapy in ABC. In this setting only a small number of retrospective and prospective (phase II) studies employing multiple different chemotherapy schedules have been conducted (level C). Thus, active symptom control (ASC) is the current standard of care after development of resistance to first-line chemotherapy. Oxaliplatin has activity in several gastrointestinal tumours and has synergistic activity with a favourable toxicity profile when used in combination with 5-FU. Several studies using mFOLFOX for biliary tract tumours have provided promising efficacy data and acceptable toxicity.

The aim of this trial is to determine if patients with ABC benefit with respect to survival from the addition of mFOLFOX chemotherapy to ASC in the second-line setting after progression to first-line treatment with CisGem. This study will establish the standard of care for patients with ABC who have progressed on first line CisGem chemotherapy.

This is a randomised phase III, multi-centre, controlled, open-label trial of patients with advanced biliary tract cancer with evidence of disease progression after prior CisGem chemotherapy treatment. Eligible patients (ECOG 0-1, adequate haematological, renal and liver function, adequate biliary drainage, with no evidence of ongoing infection) will be randomized to receive either ASC ("standard" arm) or ASC with oxaliplatin/5-FU chemotherapy ("experimental" arm). The total number of participants planned is 162 (randomized 1:1). At randomisation the following factors will be controlled for: serum albumin level, platinum sensitivity (determined from first-line therapy) and locally advanced vs metastatic disease.

The primary end point is overall survival. Quality of life and economic evaluation will assess the impact on patients and relative cost effectiveness of the intervention. Archival paraffin-embedded tissue will be collected at baseline and prospective blood samples (whole blood, serum and plasma) will be collected for translational research.

Study Type

Interventional

Enrollment (Actual)

162

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United Kingdom
      • Birmingham, United Kingdom
        • Queen Elizabeth Hospital
      • Bristol, United Kingdom
        • Bristol Haematology & Oncology Centre
      • Carlisle, United Kingdom
        • North Cumbria University Hospitals
      • Glasgow, United Kingdom, G12 0YN
        • Beatson West of Scotland Cancer Centre
      • Hull, United Kingdom
        • Castle Hill Hospital
      • Leeds, United Kingdom
        • St James' Hospital
      • Liverpool, United Kingdom
        • Clatterbridge Cancer Centre
      • London, United Kingdom
        • University College London
      • London, United Kingdom
        • Royal Free Hospital
      • London, United Kingdom
        • Hammersmith Hospital
      • London, United Kingdom
        • Guy's and St Thomas' Hospital
      • Maidstone, United Kingdom
        • Maidstone Hospital
      • Manchester, United Kingdom
        • The Christie NHS Foundation Trust
      • Nottingham, United Kingdom
        • Nottingham City Hospital
      • Oxford, United Kingdom
        • Churchill Hospital
      • Sheffield, United Kingdom
        • Weston Park Hospital
      • Southampton, United Kingdom
        • Southampton General Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Histologically / cytologically verified, non-resectable or recurrent / metastatic cholangiocarcinoma, gallbladder or ampullary carcinoma.
  • Patients must have failed no more than one prior course of chemotherapy (gemcitabine and cisplatin) with clear evidence of disease progression.
  • ECOG performance status 0-1.
  • Age >=18 years and life expectancy >3 months.
  • Adequate renal function with serum urea and serum creatinine < 1.5 times upper limit of normal (ULN) and creatinine clearance >= 30ml/min
  • Adequate haematological function: Hb >= 100g/l, WBC >= 3.0 x 10*9/L, ANC >= 2 x 10*9/L, platelet count >= 100 x 10*9/L
  • Adequate liver function: total bilirubin < 60 μmol/L and ALP, along with AST and/or ALT ≤ 5 x ULN
  • Adequate biliary drainage, with no evidence of ongoing infection (patients on maintenance antibiotics are eligible when acute sepsis has resolved).
  • Women of child bearing age must have a negative pregnancy test prior to study entry and be using an adequate contraception method, which must be continued for 4 months after the study, unless child bearing potential has been terminated by surgery/radical radiotherapy
  • Men must be willing to use an adequate method of contraception during chemotherapy and until 6 months after chemotherapy
  • Patients must have given written informed consent
  • Patients must be randomised and those allocated chemotherapy must start treatment within 6 weeks of diagnosis of disease progression

Exclusion criteria:

  • Incomplete recovery from previous therapy or unresolved biliary tree obstruction (includes ongoing neuropathy of grade >1 from cisplatin)
  • Any evidence of severe or uncontrolled systemic diseases which, in the view of the investigator, makes it undesirable for the patient to participate in the trial
  • Evidence of significant clinical disorder or laboratory finding which, in the opinion of the investigator makes it undesirable for the patient to participate in the trial
  • Any patient with a medical or psychiatric condition that impairs their ability to give informed consent
  • Any other serious uncontrolled medical conditions
  • Clinical evidence of metastatic disease to brain
  • Any pregnant or lactating woman

  • Clinically significant cardiovascular disease. [i.e. active; or <12 months since e.g. cerebrovascular accident, myocardial infarction, unstable angina, New York Heart Association (NYHA) grade II or greater congestive heart failure, serious cardiac arrhythmia requiring medication, uncontrolled hypertension].

    **Hypertension grading of ≥ 3 is an exclusion criteria (CTCAE v4.03). However, patients who have controlled hypertension with medication and/or diet may be included at the investigator's discretion. (This should be noted in the medical history section of the CRF).

  • Patients must not have a history of other malignant diseases within the last 5 years (other than adequately treated non-melanotic skin cancer or in-situ carcinoma of the uterine cervix).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Arm A: Active symptom control (ASC)
Active Symptom Control
Other: Active Symptom Control
Active Symptom Control: monthly clinical review and active symptom control as needed, including biliary drainage, antibiotics, analgesia, steroids, anti-emetics, other palliative treatment for symptom control, palliative radiotherapy, blood transfusion.
Experimental: Arm B: ASC with OxMdG chemotherapy
Active Symptom Control with OxMdG chemo (Oxaliplatin, L-folinic acid & 5FU)
Other: Active Symptom Control
Active Symptom Control: monthly clinical review and active symptom control as needed, including biliary drainage, antibiotics, analgesia, steroids, anti-emetics, other palliative treatment for symptom control, palliative radiotherapy, blood transfusion.
Drug: L-folinic acid
L-folinic acid 175mg (or folinic acid 350mg) q14d, up to 12 cycles
Other Names:
  • Folinic acid
Drug: 5 FU
5 FU 400 mg/m2 (bolus), 2400 mg/m2 (infusion), q 14d, up to 12 cycles
Other Names:
  • Fluorouracil
Drug: Oxaliplatin
Oxaliplatin 85mg/m2, q 14d, up to 12 cycles
Other Names:
  • Eloxatin

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Overall survival
Time Frame: Evaluated by monthly follow-up until 12 months after last patient included
Evaluated by monthly follow-up until 12 months after last patient included

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression-free survival
Time Frame: Evaluated by monthly follow-up until 12 months after last patient included
Clinical progression assessed monthly, radiological progression assessed to RECIST criteria every 12 weeks for patients in the chemotherapy arm.
Evaluated by monthly follow-up until 12 months after last patient included
Response rate (chemotherapy arm only)
Time Frame: After 12 weeks of treatment
After 12 weeks of treatment
Toxicity (frequency of adverse events and serious adverse events)
Time Frame: Evaluated monthly until 12 months after last patient included
Events will be classified according to CTCAE V4.03
Evaluated monthly until 12 months after last patient included
Quality of life
Time Frame: Evaluated every 3 months until 12 months after last patient included
Assessed from patient completed questionnaire data: QLQ-C30 and QoL BiL
Evaluated every 3 months until 12 months after last patient included
Costs of health and social care
Time Frame: Evaluated every 3 months until 12 months after last patient included
Evaluated every 3 months until 12 months after last patient included
Health status (Euroqol)
Time Frame: Evaluated every 3 months until 12 months after last patient included
Evaluated every 3 months until 12 months after last patient included
Quality adjusted life years (QALYs)
Time Frame: Evaluated every 3 months until 12 months after last patient included
Estimated from Euroqol and survival using published utility tariffs
Evaluated every 3 months until 12 months after last patient included

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

The Christie NHS Foundation Trust

Collaborators

Cancer Research UK

Investigators

  • Principal Investigator: Juan Valle, Prof, The Christie NHS Foundation Trust

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

February 1, 2014

Primary Completion (Actual)

January 5, 2018

Study Completion (Actual)

January 1, 2019

Study Registration Dates

First Submitted

August 17, 2013

First Submitted That Met QC Criteria

August 19, 2013

First Posted (Estimate)

August 20, 2013

Study Record Updates

Last Update Posted (Actual)

January 28, 2020

Last Update Submitted That Met QC Criteria

January 26, 2020

Last Verified

January 1, 2020

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CFTSp048
  • A16281 (Other Grant/Funding Number: Cancer Research UK (CTAAC))
  • 2013-001812-30 (EudraCT Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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