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

Phase 3

Completed

• Conditions: Ampullary Cancer; Cholangiocarcinoma; Biliary Tract Cancer; Gallbladder Cancer
• Interventions: Other: Active Symptom Control; Drug: L-folinic acid; Drug: 5 FU; Drug: Oxaliplatin

• Registration Number: NCT01926236
• Lead Sponsor: The Christie NHS Foundation Trust

Brief Summary

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.

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...

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2013-08-17
• Study First Submitted QC: 2013-08-19
• Study First Posted: 2013-08-20
• Study Start: 2014-02
• Primary Completion: 2018-01-05
• Study Completion: 2019-01
• Status Verified: 2020-01
• Last Update Submitted: 2020-01-26
• Last Update Posted: 2020-01-28

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 162

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).

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm B: ASC with OxMdG chemotherapy	Active Symptom Control	Active Symptom Control with OxMdG chemo (Oxaliplatin, L-folinic acid \& 5FU)
Arm B: ASC with OxMdG chemotherapy	L-folinic acid	Active Symptom Control with OxMdG chemo (Oxaliplatin, L-folinic acid \& 5FU)
Arm B: ASC with OxMdG chemotherapy	5 FU	Active Symptom Control with OxMdG chemo (Oxaliplatin, L-folinic acid \& 5FU)
Arm B: ASC with OxMdG chemotherapy	Oxaliplatin	Active Symptom Control with OxMdG chemo (Oxaliplatin, L-folinic acid \& 5FU)
Arm A: Active symptom control (ASC)	Active Symptom Control	Active Symptom Control

Primary Outcome Measures

Name	Time	Method
Overall survival	Evaluated by monthly follow-up until 12 months after last patient included

Secondary Outcome Measures

Name	Time	Method
Health status (Euroqol)	Evaluated every 3 months until 12 months after last patient included
Progression-free survival	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.
Response rate (chemotherapy arm only)	After 12 weeks of treatment
Toxicity (frequency of adverse events and serious adverse events)	Evaluated monthly until 12 months after last patient included	Events will be classified according to CTCAE V4.03
Quality of life	Evaluated every 3 months until 12 months after last patient included	Assessed from patient completed questionnaire data: QLQ-C30 and QoL BiL
Costs of health and social care	Evaluated every 3 months until 12 months after last patient included
Quality adjusted life years (QALYs)	Evaluated every 3 months until 12 months after last patient included	Estimated from Euroqol and survival using published utility tariffs

Trial Locations

Locations (17)

North Cumbria University Hospitals; 🇬🇧 Carlisle, United Kingdom

Maidstone Hospital; 🇬🇧 Maidstone, United Kingdom

The Christie NHS Foundation Trust; 🇬🇧 Manchester, United Kingdom

Nottingham City Hospital; 🇬🇧 Nottingham, United Kingdom

Churchill Hospital; 🇬🇧 Oxford, United Kingdom

Weston Park Hospital; 🇬🇧 Sheffield, United Kingdom

Southampton General Hospital; 🇬🇧 Southampton, United Kingdom

Beatson West of Scotland Cancer Centre; 🇬🇧 Glasgow, United Kingdom

Bristol Haematology & Oncology Centre; 🇬🇧 Bristol, United Kingdom

Hammersmith Hospital; 🇬🇧 London, United Kingdom

Queen Elizabeth Hospital; 🇬🇧 Birmingham, United Kingdom

Clatterbridge Cancer Centre; 🇬🇧 Liverpool, United Kingdom

Royal Free Hospital; 🇬🇧 London, United Kingdom

Guy's and St Thomas' Hospital; 🇬🇧 London, United Kingdom

University College London; 🇬🇧 London, United Kingdom

St James' Hospital; 🇬🇧 Leeds, United Kingdom

Castle Hill Hospital; 🇬🇧 Hull, United Kingdom