E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
ADVANCED BILIARY TRACT CANCER |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | HLGT |
E.1.2 | Classification code | 10019815 |
E.1.2 | Term | Hepatobiliary neoplasms malignant and unspecified |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Determine the efficacy of VANDETANIB monotherapy or VANDETANIB plus GEMCITABINE or PLACEBO plus GEMCITABINE in prolonging the progression-free survival (PFS) at the trial closure in patients with advanced (unresectable or metastatic) biliary tract cancer. |
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E.2.2 | Secondary objectives of the trial |
1.To define the Objective Response Rate (complete response [CR] and partial response [PR]) according to RECIST criteria for VANDETANIB monotherapy or VANDETANIB plus GEMCITABINE or PLACEBO plus GEMCITABINE 2.To define the Disease control rate (CR, PR and stable disease [SD]) according to RECIST criteria for VANDETANIB monotherapy or VANDETANIB plus GEMCITABINE or PLACEBO plus GEMCITABINE 3.To determine the overall survival (OS) at trial closure for VANDETANIB monotherapy or VANDETANIB plus GEMCITABINE or PLACEBO plus GEMCITABINE 4.To determine the Duration of response (CR, PR) for VANDETANIB monotherapy or VANDETANIB plus GEMCITABINE or PLACEBO plus GEMCITABINE 5.To assess the performance status of patients treated with VANDETANIB plus GEMCITABINE or PLACEBO plus GEMCITABINE or VANDETANIB monotherapy 6.To study the safety and tolerability of GEMCITABINE, VANDETANIB monotherapy and VANDETANIB / PLACEBO in combination with GEMCITABINE. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1.Provision of informed consent 2.Male or Female aged 18 years and over 3.Histologically or citologically-confirmed advanced (unresectable or metastatic) biliary tract cancer (gallbladder cancer, cancer of the extrahepatic bile duct, intrahepatic cholangiocarcinoma and ampullary carcinoma) excluding small cell (oat cell) carcinoma of the hepatobiliary tract. 4.Patients must have measurable or evaluable but non-measurable disease, defined as follows: - Measurable Disease - Patients with measurable disease as defined by the modified Response Evaluation Criteria in Solid Tumors (RECIST) criteria, i.e., the presence of at least one measurable lesion. A measurable lesion is one that can be accurately measured in at least one dimension with the longest diameter ≥ 20 mm using conventional techniques or ≥ 10 mm using spiral Computed Tomography (CT) scan. Clinical lesions will only be considered measurable when they are superficial (e.g., skin nodules, palpable lymph nodes). - Evaluable but Non-measurable Disease - Patients with all lesions below the limits defined above for measureable disease (i.e., longest diameter < 20 mm with conventional techniques or < 10 mm with spiral CT) excluding those patients with only a primary non-measurable lesion and/or with only non-evaluable cancer such as bone metastases, ascites, pleural or pericardia effusions, lymphangitic carcinomatosis of the skin or lung, previously irradiated lesions not in progression, or peritoneal carcinomatosis < 10 mm in diameter with conventional imaging techniques. 5.Chemotherapy-naïve (prior chemotherapy in the adjuvant setting completed more than 3 months before the trial entry is accepted). 6.WHO performance status 0 to 2: patients must have a WHO PS ≤ 2 7.Life expectancy of at least 12 weeks. 8.Negative pregnancy test for women of childbearing potential 9.Provision of informed consent for biomarker research (optional) |
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E.4 | Principal exclusion criteria |
1.Histologically or citologically-confirmed small cell (oat cell) carcinoma of the hepatobiliary tract is to be excluded. 2.Patients must not have received prior systemic therapy for advanced (unresectable or metastatic) disease; prior chemotherapy in the adjuvant setting within 3 months before the trial entry is accepted. 3.Prior treatment with VEGFR TKIs (previous treatment with bevacizumab [Avastin] is permitted) 4.Prior unanticipated severe reaction to GEMCITABINE therapy or known sensitivity to GEMCITABINE. 5.Radiation therapy within 4 weeks before the start of study therapy, not including local palliative radiation. Prior radiotherapy is accepted as long as target lesions have not been irradiated. Lesions that have received radiation in the advanced setting cannot be included as target lesions unless clear tumour progression has been documented in the lesions since the end of radiation therapy 6.Major surgery within 4 weeks, or incompletely healed surgical incision before starting study therapy or serious, non-healing wound, ulcer, or bone fracture. Insertion of a vascular access device is not considered major/minor surgery. 7.Inadequate end-organ function 8.Known brain metastases or carcinomatous meningitis. Patients with known brain metastases should be excluded from this clinical trial unless asymptomatic or with evidence of clinically SD (no steroid therapy or steroid dose being tapered) for at least 28 days. 9.Evidence of severe or uncontrolled systemic disease or any concurrent condition which in the Investigators opinion makes it undesirable for the patient to participate in the trial or which would jeopardize compliance with the protocol |
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E.5 End points |
E.5.1 | Primary end point(s) |
Progression free survival |
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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 | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | Yes |
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) | 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 | 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 | Yes |
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) | Yes |
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 | 18 |
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 | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | No |
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 | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 0 |