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

Cholangiocarcinoma Clinical Trial

— ABC06  

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01926236
• Other study ID #: CFTSp048
• Secondary ID: A162812013-00181
• Status: Completed
• Phase: Phase 3
• Start date: February 2014
• Est. completion date: January 2019

Study information

• Verified date: January 2020
• Source: The Christie NHS Foundation Trust
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 162
• Est. completion date: January 2019
• Est. primary completion date: January 5, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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).

Related Conditions & MeSH terms

• Ampullary Cancer
• Biliary Tract Cancer
• Biliary Tract Neoplasms
• Cholangiocarcinoma
• Gallbladder Cancer
• Gallbladder Neoplasms

Intervention

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
• 5 FU
5 FU 400 mg/m2 (bolus), 2400 mg/m2 (infusion), q 14d, up to 12 cycles
• Oxaliplatin
Oxaliplatin 85mg/m2, q 14d, up to 12 cycles

Locations

Country	Name	City	State
United Kingdom	Queen Elizabeth Hospital	Birmingham
United Kingdom	Bristol Haematology & Oncology Centre	Bristol
United Kingdom	North Cumbria University Hospitals	Carlisle
United Kingdom	Beatson West of Scotland Cancer Centre	Glasgow
United Kingdom	Castle Hill Hospital	Hull
United Kingdom	St James' Hospital	Leeds
United Kingdom	Clatterbridge Cancer Centre	Liverpool
United Kingdom	Guy's and St Thomas' Hospital	London
United Kingdom	Hammersmith Hospital	London
United Kingdom	Royal Free Hospital	London
United Kingdom	University College London	London
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

Sponsors (2)

Lead Sponsor	Collaborator
The Christie NHS Foundation Trust	Cancer Research UK

Country where clinical trial is conducted

United Kingdom, 

Outcome

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

External Links

•   ABC-06 on Cancer Research UK's trial database for patients