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

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2014 by Christie Hospital NHS Foundation Trust
Sponsor:
Collaborator:
Cancer Research UK
Information provided by (Responsible Party):
Rebecca Robinson, Christie Hospital NHS Foundation Trust
ClinicalTrials.gov Identifier:
NCT01926236
First received: August 17, 2013
Last updated: October 20, 2014
Last verified: October 2014

August 17, 2013
October 20, 2014
February 2014
June 2017   (final data collection date for primary outcome measure)
Overall survival [ Time Frame: Evaluated by monthly follow-up until 12 months after last patient included ] [ Designated as safety issue: No ]
Same as current
Complete list of historical versions of study NCT01926236 on ClinicalTrials.gov Archive Site
  • 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 (Euroqol) [ 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 Euroqol and survival using published utility tariffs
  • 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
Not Provided
Not Provided
 
Active Symptom Control Alone or With mFOLFOX Chemotherapy for Locally Advanced/ Metastatic Biliary Tract Cancers
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.

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.

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Biliary Tract Cancer
  • Gallbladder Cancer
  • Cholangiocarcinoma
  • Ampullary Cancer
  • 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
  • Active Comparator: Arm A: Active symptom control (ASC)
    Active Symptom Control
    Intervention: Other: Active Symptom Control
  • Experimental: Arm B: ASC with OxMdG chemotherapy
    Active Symptom Control with OxMdG chemo (Oxaliplatin, L-folinic acid & 5FU)
    Interventions:
    • Other: Active Symptom Control
    • Drug: L-folinic acid
    • Drug: 5 FU
    • Drug: Oxaliplatin
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
162
June 2017
June 2017   (final data collection date for primary outcome measure)

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).
Both
18 Years and older
No
Contact: Rebecca Robinson ABC06@christie.nhs.uk
United Kingdom
 
NCT01926236
CFTSp048, A16281, 2013-001812-30
Yes
Rebecca Robinson, Christie Hospital NHS Foundation Trust
Christie Hospital NHS Foundation Trust
Cancer Research UK
Principal Investigator: Juan Valle, Prof The Christie NHS Foundation Trust
Christie Hospital NHS Foundation Trust
October 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP