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 | 20.0 |
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 | 20.0 |
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 |
The primary objective of this study is to evaluate the efficacy of gemcitabine and cisplatin compared with observation treatment in patients with BTC after complete resection in terms of DFS.
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E.2.2 | Secondary objectives of the trial |
Secondary objectives are safety and tolerability of the treatment as well as OS, quality of life, function of biliodigestive anastomoses, and evaluation of the quantity and quality of information patients have gained after the informed consent as well as of the involvement of patients in the decision-making process (shared decision making). |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Eligibility criteria for treatment phase (before randomization)
1. Histologically confirmed adenocarcinoma of biliary tract (intrahepatic, hilar or extrahepatic cholangiocarcinoma or muscle invasive gallbladder carcinoma) after radical surgical therapy with macroscopically complete resection (mixed tumor entities (HCC/CCA) 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 hematologic function: ANC ≥ 1.5 x 10^9/L, platelets ≥ 100 x10^9/L, hemoglobin ≥ 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 randomization
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 |
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E.4 | Principal exclusion criteria |
1. Prior chemotherapy for biliary tract cancer
2.Previous malignancy within 3 years or concomitant malignancy, except: non-melanomatous skin cancer or adequately treated in situ cervical cancer
3. 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)
4. Psychiatric disorder precluding understanding of information of trial related topics and giving informed consent
5. Serious underlying medical conditions (judged by the investigator), that could impair the ability of the patient to participate in the trial
6. Fertile women (< 1 year after last menstruation) and procreative men not willing or unable to use effective means of contraception (oral contraceptives, intrauterine contraceptive device, barrier method of contraception in conjunction with spermicidal jelly or surgically sterile)
7. Pregnant or lactating women
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E.5 End points |
E.5.1 | Primary end point(s) |
Disease free survival (DFS) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Every three months up to 24 month |
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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 |
Every three months for two years after randomization followed by 6 monthly for 3 years |
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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 | No |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
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 | No |
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 | 2 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
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 | |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |