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

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ClinicalTrials.gov Identifier: NCT01926236
Recruitment Status : Completed
First Posted : August 20, 2013
Last Update Posted : January 28, 2020
Sponsor:
Collaborator:
Cancer Research UK
Information provided by (Responsible Party):
Juan Valle, The Christie NHS Foundation Trust

Study Description
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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.

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

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.

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 162 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (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.
Study Start Date : February 2014
Actual Primary Completion Date : January 5, 2018
Actual Study Completion Date : January 2019

Resource links provided by the National Library of Medicine

Drug Information available for: Oxaliplatin

Arms and Interventions
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Arm Intervention/treatment
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


Outcome Measures
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Primary Outcome Measures :
  1. Overall survival [ Time Frame: Evaluated by monthly follow-up until 12 months after last patient included ]

Secondary Outcome Measures :
  1. Progression-free survival [ Time Frame: 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.

  2. Response rate (chemotherapy arm only) [ Time Frame: After 12 weeks of treatment ]
  3. Toxicity (frequency of adverse events and serious adverse events) [ Time Frame: Evaluated monthly until 12 months after last patient included ]
    Events will be classified according to CTCAE V4.03

  4. Quality of life [ Time Frame: Evaluated every 3 months until 12 months after last patient included ]
    Assessed from patient completed questionnaire data: QLQ-C30 and QoL BiL

  5. Costs of health and social care [ Time Frame: Evaluated every 3 months until 12 months after last patient included ]
  6. Health status (Euroqol) [ Time Frame: Evaluated every 3 months until 12 months after last patient included ]
  7. Quality adjusted life years (QALYs) [ Time Frame: Evaluated every 3 months until 12 months after last patient included ]
    Estimated from Euroqol and survival using published utility tariffs


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
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 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).
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01926236


Locations
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Sponsors and Collaborators
The Christie NHS Foundation Trust
Cancer Research UK
Investigators
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Principal Investigator: Juan Valle, Prof The Christie NHS Foundation Trust
More Information
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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Juan Valle, Medical Oncologist, The Christie NHS Foundation Trust
ClinicalTrials.gov Identifier: NCT01926236    
Other Study ID Numbers: CFTSp048
A16281 ( Other Grant/Funding Number: Cancer Research UK (CTAAC) )
2013-001812-30 ( EudraCT Number )
First Posted: August 20, 2013    Key Record Dates
Last Update Posted: January 28, 2020
Last Verified: January 2020
Additional relevant MeSH terms:
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Cholangiocarcinoma
Biliary Tract Neoplasms
Gallbladder Neoplasms
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Biliary Tract Diseases
Digestive System Diseases
Gallbladder Diseases
Leucovorin
Folic Acid
 Fluorouracil
Oxaliplatin
Levoleucovorin
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Antineoplastic Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antidotes
Protective Agents
Vitamin B Complex
Vitamins
Micronutrients