Locally advanced biliary tract cancer MedDRA version: 21.0 Level: LLT Classification code 10004586 Term: Bile duct adenocarcinoma non-resectable System Organ Class: 100000004864 MedDRA version: 20.0 Level: LLT Classification code 10008594 Term: Cholangiocarcinoma non-resectable System Organ Class: 100000004864
Conditions
Interventions
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: cisplatin
CAS Number: 15663-27-1
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentrati
Sponsors
University College London
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. A histopathological/cytological diagnosis of locally advanced, non-resectable biliary tract carcinoma (intra- or extra-hepatic), (excluding cancer of the gall bladder and ampullary carcinoma) 2. Not suitable for radical surgery, or medically unfit for surgery as decided by a hepatobiliary MDT 3. Tumour visible on cross-sectional imaging 4. Measurable disease (according to RECIST criteria v1.1). (If disease is not measurable using RECIST v1.1, the tumour must be visible for targeting with radiation). 5. Tumour (and nodes if involved) must be =12 cm in the longest dimension. For patients with non-measurable disease, sites should use the CT reconstructions (coronal or sagittal views) to measure tumour size. 6. Adequate biliary drainage 7. WHO PS 0 or 1 8. Adequate haematological function: • Haemoglobin = 100 g/L (the use of transfusion to achieve desired Hb is acceptable) • White blood cell count (WBC) = 3.0 x 109/L • Absolute neutrophil count (ANC) =1.5 x 109/L • Platelet count = 100 x 109/L 9. Adequate liver function: • Total bilirubin =3.0 x ULN. Total bilirubin levels must be considered stable by the treating clinician e.g. more than one reading is required to show they are stable. Exceptions are possible for patients with known documented cases of Gilbert’s syndrome, as long as the Bilirubin is stable and the treating clinician feels that the increased bilirubin is not due to obstruction or cholangitis. • ALT and/or AST = 2.5 x ULN • ALP = 5 x ULN • Albumin > 25 g/L 10. Adequate renal function: • Serum urea 12 weeks 12. 16 years of age or over 13. Patients may have had prior chemotherapy as long as patient meets all other inclusion/exclusion criteria. 14. Patient must have given written informed consent Are the trial subjects under 18? yes Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 40 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 40
Exclusion criteria
Exclusion criteria: 1. Metastatic disease 2. Direct tumour extension in the duodenum, stomach, small bowel or large bowel. 3. Previous abdominal radiotherapy or previous selective internal radiotherapy such as hepatic arterial Yttrium therapy 4. Previous hypersensitivity to platinum salts 5. 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 (including diabetes with established sensory peripheral neuropathy, unstable or uncompensated respiratory, cardiac, hepatic or renal disease) 5. 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 (including diabetes with established sensory peripheral neuropathy, unstable or uncompensated respiratory, cardiac, hepatic or renal disease) 6. Patients who have a concurrent malignancy that is clinically unstable and requires tumour-directed treatment are not eligible. Exceptions include low grade malignancies that do not require active treatment, such as early prostate cancer under surveillance or chronic lymphocytic leukaemia. 7. History of prior malignancy that could interfere with the response evaluation or survival. Exceptions include: • in-situ carcinoma of the cervix treated by cone-biopsy/resection, • non-metastatic basal and/or squamous cell carcinomas of the skin, • any early stage malignancy diagnosed over two years ago and radically treated. 7 8. Other concomitant anti-cancer therapy (except steroids) 9. Any psychiatric or other disorder likely to impact on informed consent. 10. Women who are pregnant or breast feeding NB. Whilst not excluded, patients with significant hearing impairment must be made aware of potential ototoxicity and may choose not to be included. If included, it is recommended that audiograms be carried out at baseline and prior cycle 2 of CisGem
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Feasibility: The main objective of the feasibility part of the trial is to determine if it is feasible to deliver SBRT in a multicentre trial setting in a rare disease. In particular, will clinicians recruit to the trial and will sufficient patients accept randomisation. Phase II: The main objective of this trial to find out if giving SBRT after chemotherapy is better than giving chemotherapy on its own to treat patients with locally advanced biliary tract cancer (BTC).;Secondary Objective: Feasibility: Compare the side effects in each arm To find out if giving SBRT after chemotherapy is better than giving chemotherapy on its own To find out if giving chemotherapy followed by SBRT can make disease which is inoperable operable following treatment To compare the quality of life in each arm Phase II Compare the side effects in each arm To find out if giving chemotherapy followed by SBRT can make disease which is inoperable operable following treatment To compare the quality of life in each arm ;Primary end point(s): Feasibility: An average recruitment rate of at least 1 patient per month once 6 sites have been activated. Phase II: Progression free survival ;Timepoint(s) of evaluation of this end point: Feasibility: The primary endpoint is the monthly rate of recruitment into the trial once all required sites have been activated (approximately 6 months after activation of the first site). The decision to move from feasibility into the full randomised phase II will be based upon achieving the target recruitment rate of 1 patient/month. In February 2017 the TMG agreed to expand the patient population to include patients with tumours up to 12 cm. The change in this inclusion criteria has no effect on the sample size assumptions and therefore there is no change to the sample size required. If the target recruitment remains unachievable after approximately 18 months recruitment in total, then we would conclude that the trial is not feasible. | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: Worse grade of AE (CTCAE 4.03)- Days 1 & 8 of chemotherapy, pre and during SBRT, end of treatment and at 3 month and 6 month follow up Pattern of treatment failure- end of treatment Best overall response- Every 3 months until progression Progression Free Survival - 9 months after randomisation Overall Survival- death Quality of Life- Every 3 months until progression Downstaging permitting surgery- 1 month post SBRT Time to treatment failure - very 3 months until progression/death/patient starts new treatment ;Secondary end point(s): Feasibility: Worse grade of AE (CTCAE 4.03) Pattern of treatment failure Best overall response (RECIST v1.1) Progression Free Survival at 9 months after randomisation Progression Free Survival Overall Survival Quality of Life Achieving downstaging permitting surgery Time to treatment failure Phase II: Worse grade of AE (CTCAE 4.03) Pattern of treatment failure Best overall response (RECIST v1.1) Duration of response Progression Free Survival at 9 months after randomisation Overall Survival Quality of Life Downstaging permitting surgery Time to treatment failure | — |
Countries
United Kingdom
Contacts
Public ContactABC-07 Trial Coordinator
CR UK & UCL Cancer Trials Centre
Outcome results
None listed