E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Cholangiocarcinoma and gallbladder carcinoma |
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E.1.1.1 | Medical condition in easily understood language |
Carcinoma of the bile ducts and gallbladder carcinoma |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10017620 |
E.1.2 | Term | Gallbladder carcinoma |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10008593 |
E.1.2 | Term | Cholangiocarcinoma |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
We would like to know whether or not treating patients with Cisplatin and Gemcitabine (chemotherapy) helps reduce the risk of biliary tract or gallbladder cancer returning. |
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E.2.2 | Secondary objectives of the trial |
The patient experience during and after chemotherapy is important to describe in the ACTICCA-1 trial. A standard Quality of life (QoL) evaluation will be performed and patients will be requested to complete the QoL form at specific time points during and after treatment. Toxicity and side effects for patients on chemotherapy will be collected and reviewed to ensure patient safety. The collection of biliary and digestive complications relating to patients surgical reconstructions and requirement for further intervention will be performed. The research question will look to compare the impact of chemotherapy against the control group in assessing overall survival. Disease free survival at two years post randomisation will also be analyzed. Where recurrence, and documentation of cancers returning, occurs the locations and patterns for cancers returning will be collated and analyzed. The translational objective will be to build a tissue and sample repository from consented patients t |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
ACTICCA-1 Translational Research substudy Investigation of the information content of the informed consent and the shared decision-making process Substudy. These substudies are integral to the main trial protocol and thus has the same version number and date. |
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E.3 | Principal inclusion criteria |
Eligibility criteria for enrolment phase 1. Suspicion of or histologically/cytologically confirmed adenocarcinoma of biliary tract (intrahepatic, hilar or extrahepatic biliary tract cancer, or muscle invasive gallbladder cancer) scheduled for radical surgical therapy 2. Written informed consent 3. No prior chemotherapy for biliary tract cancer 4. No previous malignancy within 3 years or concomitant malignancy, except: non-melanomatous skin cancer or adequately treated in situ cervical cancer 5. No severe or uncontrolled cardiovascular disease (congestive heart failure NYHA III or IV, unstable angina pectoris, history of myocardial infarction in the last 3 months, significant arrhythmia) 6. Absence of psychiatric disorder precluding understanding of information of trial related topics and giving informed consent 7. No serious underlying medical conditions (judged by the investigator), that could impair the ability of the patient to participate in the trial 8. Fertile women (< 1 year after last menstruation) and procreative men willing and able to use effective means of contraception (oral contraceptives, intrauterine contraceptive device, barrier method of contraception in conjunction with spermicidal jelly or surgically sterile) 9. No pregnancy or lactation Eligibility criteria for treatment phase (before randomisation) 1. Histologically confirmed adenocarcinoma of biliary tract (intrahepatic, hilar or extrahepatic biliary tract cancer or muscle invasive gallbladder cancer) after radical surgical therapy with macroscopically complete resection (mixed hepatocellular tumours are excluded) 2. Macroscopically complete resection (R0/1) within 6 (-16) weeks before scheduled start of chemotherapy 3. ECOG 0-1 4. Age >18 years 5. Adequate haematologic function: ANC ≥1.5 x 109/L, platelets ≥100 x109/L, haemoglobin ≥9 g/dl or ≥5.59 mmol/L 6. Adequate liver function as measured by serum transaminases (AST and ALT) ≤5 x ULN and bilirubin ≤3 x ULN 7. Adequate renal function, i.e. serum creatinine ≤1.5 x ULN, glomerular filtration rate ≥ 60 mL/min (MDRD) 8. No active uncontrolled infection, except chronic viral hepatitis under antiviral therapy 9. No concurrent treatment with other experimental drugs or other anti-cancer therapy, treatment in a clinical trial within 30 days prior to randomisation 10. Negative serum pregnancy test within 7 days of starting study treatment in pre-menopausal women and women <1 year after the onset of menopause (Note: a negative test has to be reconfirmed by a urine test, should the 7-day window be exceeded) 11. Written informed consent 12. No prior chemotherapy for biliary tract cancer 13. No previous malignancy within 3 years or concomitant malignancy, except: non-melanomatous skin cancer or adequately treated in situ cervical cancer 14. No severe or uncontrolled cardiovascular disease (congestive heart failure NYHA III or IV, unstable angina pectoris, history of myocardial infarction in the last 3 months, significant arrhythmia) 15. Absence of psychiatric disorder precluding understanding of information of trial related topics and giving informed consent 16. No serious underlying medical conditions (judged by the investigator), that could impair the ability of the patient to participate in the trial 17. Fertile women (< 1 year after last menstruation) and procreative men willing and able to use effective means of contraception (oral contraceptives, intrauterine contraceptive device, barrier method of contraception in conjunction with spermicidal jelly or surgically sterile) 18. No pregnancy or lactation |
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E.4 | Principal exclusion criteria |
Mixed hepatocellular tumours are excluded. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoint will be disease free survival |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
All Patients will be followed every 3 months via CT or MRI for two years followed by 6 monthly abdominal ultrasound for further 3 years, together with clinical evaluation, and determination of CA 19-9. Additionally patients randomized to receive chemotherapy will have gemcitabine and cisplatin administered every three weeks on days 1 and 8 up to a maximum of 8 cycles. |
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E.5.2 | Secondary end point(s) |
• Disease free survival rate at 24 months (DFSR@24) • Overall survival (OS) • Safety and tolerability of adjuvant chemotherapy • Quality of life (QoL) • Function of biliodigestive anastomosis (in terms of surgical revision, requirement for PTCD) • Rate and severity of biliary tract infections • Patterns of disease recurrence • Locoregional control
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
All Patients will be followed every 3 months via CT or MRI for two years followed by 6 monthly abdominal ultrasound for further 3 years, together with clinical evaluation, and determination of CA 19-9. Additionally patients randomized to receive chemotherapy will have gemcitabine and cisplatin administered every three weeks on days 1 and 8 up to a maximum of 8 cycles. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
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E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 20 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 41 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 5 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 1 |
E.8.9.2 | In all countries concerned by the trial years | 8 |
E.8.9.2 | In all countries concerned by the trial months | 1 |
E.8.9.2 | In all countries concerned by the trial days | 1 |