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

NCT ID: NCT01926236

Last Updated: 2020-01-28

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

162 participants

Study Classification

INTERVENTIONAL

Study Start Date

2014-02-28

Study Completion Date

2019-01-31

Brief Summary

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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

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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.

Conditions

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Biliary Tract Cancer Gallbladder Cancer Cholangiocarcinoma Ampullary Cancer

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Arm A: Active symptom control (ASC)

Active Symptom Control

Group Type ACTIVE_COMPARATOR

Active Symptom Control

Intervention Type OTHER

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.

Arm B: ASC with OxMdG chemotherapy

Active Symptom Control with OxMdG chemo (Oxaliplatin, L-folinic acid \& 5FU)

Group Type EXPERIMENTAL

Active Symptom Control

Intervention Type OTHER

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.

L-folinic acid

Intervention Type DRUG

L-folinic acid 175mg (or folinic acid 350mg) q14d, up to 12 cycles

5 FU

Intervention Type DRUG

5 FU 400 mg/m2 (bolus), 2400 mg/m2 (infusion), q 14d, up to 12 cycles

Oxaliplatin

Intervention Type DRUG

Oxaliplatin 85mg/m2, q 14d, up to 12 cycles

Interventions

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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.

Intervention Type OTHER

L-folinic acid

L-folinic acid 175mg (or folinic acid 350mg) q14d, up to 12 cycles

Intervention Type DRUG

5 FU

5 FU 400 mg/m2 (bolus), 2400 mg/m2 (infusion), q 14d, up to 12 cycles

Intervention Type DRUG

Oxaliplatin

Oxaliplatin 85mg/m2, q 14d, up to 12 cycles

Intervention Type DRUG

Other Intervention Names

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Folinic acid Fluorouracil Eloxatin

Eligibility Criteria

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

* 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).
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Cancer Research UK

OTHER

Sponsor Role collaborator

The Christie NHS Foundation Trust

OTHER

Sponsor Role lead

Responsible Party

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Juan Valle

Medical Oncologist

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Juan Valle, Prof

Role: PRINCIPAL_INVESTIGATOR

The Christie NHS Foundation Trust

Locations

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Queen Elizabeth Hospital

Birmingham, , United Kingdom

Site Status

Bristol Haematology & Oncology Centre

Bristol, , United Kingdom

Site Status

North Cumbria University Hospitals

Carlisle, , United Kingdom

Site Status

Beatson West of Scotland Cancer Centre

Glasgow, , United Kingdom

Site Status

Castle Hill Hospital

Hull, , United Kingdom

Site Status

St James' Hospital

Leeds, , United Kingdom

Site Status

Clatterbridge Cancer Centre

Liverpool, , United Kingdom

Site Status

Guy's and St Thomas' Hospital

London, , United Kingdom

Site Status

Hammersmith Hospital

London, , United Kingdom

Site Status

Royal Free Hospital

London, , United Kingdom

Site Status

University College London

London, , United Kingdom

Site Status

Maidstone Hospital

Maidstone, , United Kingdom

Site Status

The Christie NHS Foundation Trust

Manchester, , United Kingdom

Site Status

Nottingham City Hospital

Nottingham, , United Kingdom

Site Status

Churchill Hospital

Oxford, , United Kingdom

Site Status

Weston Park Hospital

Sheffield, , United Kingdom

Site Status

Southampton General Hospital

Southampton, , United Kingdom

Site Status

Countries

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United Kingdom

References

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Lamarca A, Palmer DH, Wasan HS, Ross PJ, Ma YT, Arora A, Falk S, Gillmore R, Wadsley J, Patel K, Anthoney A, Maraveyas A, Iveson T, Waters JS, Hobbs C, Barber S, Ryder WD, Ramage J, Davies LM, Bridgewater JA, Valle JW; Advanced Biliary Cancer Working Group. Second-line FOLFOX chemotherapy versus active symptom control for advanced biliary tract cancer (ABC-06): a phase 3, open-label, randomised, controlled trial. Lancet Oncol. 2021 May;22(5):690-701. doi: 10.1016/S1470-2045(21)00027-9. Epub 2021 Mar 30.

Reference Type DERIVED
PMID: 33798493 (View on PubMed)

Other Identifiers

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A16281

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

2013-001812-30

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CFTSp048

Identifier Type: -

Identifier Source: org_study_id

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