E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Unresectable intrahepatic cholangiocarcinoma |
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E.1.1.1 | Medical condition in easily understood language |
Inoperable bileduct cancer in the liver. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
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 efficacy, expressed by OS, of HAIP chemotherapy and concurrent systemic chemotherapy in patient with unresectable ICC in the Netherlands. |
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E.2.2 | Secondary objectives of the trial |
Secondary objectives include postoperative complications, chemotherapy related adverse events, progression free survival (PFS), response rate, conversion to resection rate, quality of life, and cost-effectiveness. The accuracy of CT angiography to detect extrahepatic perfusion will be measured. Next, we aim to identify predictive biomarkers for the efficacy of HAIP chemotherapy |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Age ≥ 18 years. • ECOG performance status 0 or 1 (Appendix A). • Histologically confirmed diagnosis of intrahepatic cholangiocarcinoma (ICC). • Unresectable ICC confined to the liver (<70% of the liver involved) with or without limited regional lymph node disease (portal) at initial presentation, as confirmed by HPB surgeons. Regional lymph nodes will be allowed, provided it is amenable to resection. Unresectability confirmed: o Radiologically o Or during surgical exploration in patients initially considered candidates for resection • Patient is able to undergo a laparotomy or minimal-invasive surgery for pump placement. • Positioning of a catheter for HAIP chemotherapy is technically feasible (see chapter 5) based on a CT with excellent arterial phase. The default site for the catheter insertion is the gastroduodenal artery (GDA). Accessory or aberrant hepatic arteries are no contraindication for catheter placement. • Adequate bone marrow, liver and renal function as assessed by the following laboratory requirements to be conducted within 15 days prior to inclusion: o absolute neutrophil count (ANC) ≥1.5 x 109/L o platelets ≥100 x 109/L o HB ≥ 5.5 mmol/L o Total bilirubin ≤ 1.5 UNL o ASAT ≤ 5 x UNL o ALAT ≤ 5 x UNL o alkaline phosphatase ≤ 5 x UNL o (calculated) glomerular filtration rate (GFR) >50 ml/min. • Written informed consent must be given according to ICH/GCP, and national/local regulations.
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E.4 | Principal exclusion criteria |
• Presence of extrahepatic disease at the time of first presentation. Patients with limited (portal) lymph node disease, patients with small (≤ 1 cm) extrahepatic lesions that are too small to characterize are eligible. • Second primary malignancy, adequately treated non-melanoma skin cancer, or other malignancy treated at least 5 years previously without evidence of recurrence. • Failure to prior chemotherapeutical regime for cholangiocarcinoma. • Known DYPD deficiency • Prior hepatic radiation, ablation, or resection for cholangiocarcinoma. • Known intolerance to gemcitabine or cisplatin. • Life expectancy of less than 12 weeks • Clinical evidence of portal hypertension (ascites, gastroesophageal varices, or portal vein thrombosis). Surgically related ascites does not exclude the patient. • (Partial) portal vein thrombosis • Pregnant or lactating women. • History of psychiatric disability judged by the investigator to be clinically significant, precluding informed consent or interfering with compliance for HAIP chemotherapy. • Serious concomitant systemic disorders that would compromise the safety of the patient or his/her ability to complete the study, at the discretion of the investigator. • Organ allografts requiring immunosuppressive therapy. • Serious, non-healing wound, ulcer, or bone fracture. • Chronic treatment with corticosteroids (dose of ≥ 10 mg/day methylprednisolone equivalent excluding inhaled steroids). • Serious infections (uncontrolled or requiring treatment). • Participation in another investigational drug or participation in another interventional study. • Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is one-year overall survival (OS). |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1 year after inclusion of the last patient. |
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E.5.2 | Secondary end point(s) |
• Postoperative complications (Clavien-Dindo classification, grade III or higher, appendix F) • Chemotherapy related adverse events (chemotherapy related according CTCAE, grade III or higher, appendix E) • Progression free survival, is defined as the interval between surgery (pump implantation) and the earliest occurrence of disease progression. Either progression based on the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria, or the confirmed emerge of local non-primary, metastastic, or nodal disease. • Response rate, is measured according to the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria. Response rate is defined as a complete reponse, a partial response, or stable disease. • Conversion to resection rate, defined as the rate of patients who will receive a resection of the ICC after study treatment. • Quality of life measured with QLQ-C30 (appendix C), EQ-5D (appendix D) • Cost-effectiveness • Accuracy of CT angiography to detect extrahepatic perfusion • To identify biomarkers that predict the efficacy of HAIP chemotherapy
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
After inclusion of the last patient, one year after inclusion of the last patient, 2 years after inclusion of the last patient and 5 years after inclusion of the last patient. |
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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 | Yes |
E.6.13.1 | Other scope of the trial description |
Predictive value of biomarkers |
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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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
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 | Yes |
E.8.1.7.1 | Other trial design description |
Prospective single-arm interventional study. |
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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.8.3 |
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 | 4 |
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 | 4 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |