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

This study is currently recruiting participants.
Verified March 2014 by Christie Hospital NHS Foundation Trust
Sponsor:
Collaborator:
Cancer Research UK
Information provided by (Responsible Party):
Juan Valle, Christie Hospital NHS Foundation Trust
ClinicalTrials.gov Identifier:
NCT01926236
First received: August 17, 2013
Last updated: March 29, 2014
Last verified: March 2014
  Purpose

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.


Condition Intervention Phase
Biliary Tract Cancer
Gallbladder Cancer
Cholangiocarcinoma
Ampullary Cancer
Other: Active Symptom Control
Drug: L-folinic acid
Drug: 5 FU
Drug: Oxaliplatin
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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.

Resource links provided by NLM:


Further study details as provided by Christie Hospital NHS Foundation Trust:

Primary Outcome Measures:
  • Overall survival [ Time Frame: Evaluated by monthly follow-up until 12 months after last patient included ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Progression-free survival [ Time Frame: Evaluated by monthly follow-up until 12 months after last patient included ] [ Designated as safety issue: No ]
    Clinical progression assessed monthly, radiological progression assessed to RECIST criteria every 12 weeks for patients in the chemotherapy arm.

  • Response rate (chemotherapy arm only) [ Time Frame: After 12 weeks of treatment ] [ Designated as safety issue: No ]
  • Toxicity (frequency of adverse events and serious adverse events) [ Time Frame: Evaluated monthly until 12 months after last patient included ] [ Designated as safety issue: Yes ]
    Events will be classified according to CTCAE V4.03

  • Quality of life [ Time Frame: Evaluated every 3 months until 12 months after last patient included ] [ Designated as safety issue: No ]
    Assessed from patient completed questionnaire data: QLQ-C30 and QoL BiL

  • Costs of health and social care [ Time Frame: Evaluated every 3 months until 12 months after last patient included ] [ Designated as safety issue: No ]
  • Health status (Eurqol) [ Time Frame: Evaluated every 3 months until 12 months after last patient included ] [ Designated as safety issue: No ]
  • Quality adjusted life years (QALYs) [ Time Frame: Evaluated every 3 months until 12 months after last patient included ] [ Designated as safety issue: No ]
    Estimated from Eurqol and survival using published utility tariffs


Estimated Enrollment: 162
Study Start Date: February 2014
Estimated Study Completion Date: June 2017
Estimated Primary Completion Date: June 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: Folinic acid
Drug: 5 FU
5 FU 400 mg/m2 (bolus), 2400 mg/m2 (infusion), q 14d, up to 12 cycles
Other Name: Fluorouracil
Drug: Oxaliplatin
Oxaliplatin 85mg/m2, q 14d, up to 12 cycles
Other Name: Eloxatin

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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 umol/L and ALT, AST & alkaline phosphatase <= 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 not have a history of other malignant diseases other than adequately treated non-melanotic skin cancer or in-situ carcinoma of the uterine cervix
  • Patients must have given written informed consent
  • Patients must be randomised within 4 weeks of the diagnosis of radiological progression; and patients 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].
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01926236

Contacts
Contact: Helen Flight ABC06@christie.nhs.uk
Contact: Rebecca Robinson ABC06@christie.nhs.uk

Locations
United Kingdom
Queen Elizabeth Hospital Not yet recruiting
Birmingham, United Kingdom
Principal Investigator: Yuk Ting Ma, Dr         
Bristol Haematology & Oncology Centre Not yet recruiting
Bristol, United Kingdom
Principal Investigator: Stephen Falk, Dr         
Addenbrooke's Hospital Not yet recruiting
Cambridge, United Kingdom
Principal Investigator: Pippa Corrie, Dr         
North Cumbria University Hospitals Recruiting
Carlisle, United Kingdom
Principal Investigator: Jonathan Nicoll, Dr         
Cheltenham General Hospital Not yet recruiting
Cheltenham, United Kingdom
Principal Investigator: Sean Elyan, Dr         
Castle Hill Hospital Not yet recruiting
Hull, United Kingdom
Principal Investigator: Anthony Maraveyas, Dr         
St James' Hospital Not yet recruiting
Leeds, United Kingdom
Principal Investigator: Fiona Collinson, Dr         
Clatterbridge Cancer Centre Recruiting
Liverpool, United Kingdom
Principal Investigator: Daniel Palmer, Prof         
University College London Not yet recruiting
London, United Kingdom
Principal Investigator: John Bridgewater, Dr         
Royal Free Hospital Not yet recruiting
London, United Kingdom
Principal Investigator: Roopinder Gillmore, Dr         
Guy's and St Thomas' Hospital Not yet recruiting
London, United Kingdom
Principal Investigator: Paul Ross, Dr         
Hammersmith Hospital Not yet recruiting
London, United Kingdom
Principal Investigator: Harpreet Wasan, Dr         
Maidstone Hospital Not yet recruiting
Maidstone, United Kingdom
Principal Investigator: Justin Waters, Dr         
The Christie NHS Foundation Trust Recruiting
Manchester, United Kingdom
Principal Investigator: Juan Valle, Prof         
Nottingham City Hospital Not yet recruiting
Nottingham, United Kingdom
Principal Investigator: Vicky Brown, Dr         
Churchill Hospital Not yet recruiting
Oxford, United Kingdom
Principal Investigator: Kinnari Patel, Dr         
Weston Park Hospital Not yet recruiting
Sheffield, United Kingdom
Principal Investigator: Jonathan Wadsley, Dr         
Southampton General Hospital Recruiting
Southampton, United Kingdom
Principal Investigator: Tim Iveson, Dr         
Great Western Hospital Not yet recruiting
Swindon, United Kingdom
Principal Investigator: Claire Blesing, Dr         
Sponsors and Collaborators
Christie Hospital NHS Foundation Trust
Cancer Research UK
Investigators
Principal Investigator: Juan Valle, Prof The Christie NHS Foundation Trust
  More Information

Additional Information:
No publications provided

Responsible Party: Juan Valle, Professor of Medical Oncology, Christie Hospital NHS Foundation Trust
ClinicalTrials.gov Identifier: NCT01926236     History of Changes
Other Study ID Numbers: CFTSp048, A16281, 2013-001812-30
Study First Received: August 17, 2013
Last Updated: March 29, 2014
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

Additional relevant MeSH terms:
Gallbladder Neoplasms
Cholangiocarcinoma
Biliary Tract Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Biliary Tract Diseases
Digestive System Diseases
Gallbladder Diseases
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Fluorouracil
Oxaliplatin
Leucovorin
Folic Acid
Levoleucovorin
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antimetabolites, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Vitamin B Complex
Vitamins
Micronutrients

ClinicalTrials.gov processed this record on April 17, 2014