E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
advanced or metastatic cholangiocarcinoma
FGFR2 gene fusion,
FGFR genetic alteration |
|
E.1.1.1 | Medical condition in easily understood language |
|
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 | 17.0 |
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) |
|
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 |
To evaluate the efficacy of single agent BGJ398 in patients with advanced or metastatic cholangiocarcinoma with FGFR2 gene fusions/translocations or other FGFR genetic alterations assessed by investigator as per RECIST v1.1. |
|
E.2.2 | Secondary objectives of the trial |
-To further evaluate the efficacy of single agent BGJ398 as measured by
progression free survival, best overall response, disease control rate,
overall survival assessed by investigator as per RECIST 1.1
- To characterize the safety and tolerability of single agent BGJ398 by the type, frequency and severity of AEs & SAEs.
- To determine selected trough and 2-hr plasma concentrations of BGJ398 |
|
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 |
Title:Optional Tumor Biomarker assessment
Version: 00
Date: 21-02-2014
Objective: Evaluation of tumor biomarkers |
|
E.3 | Principal inclusion criteria |
- Patients with histologically or cytologically confirmed cholangiocarcinoma at the time of diagnosis.
- Patients must have received at least one prior regimen containing gemcitabine with or without cisplatin for advanced or metastatic disease. Patient must have evidence of progressive disease following prior regimen.
Other protocol defined criteria may apply |
|
E.4 | Principal exclusion criteria |
- Prior or current treatment with an FGFR inhibitor
- insufficient organ function •ANC < 1,000/mm3 [1.0 x 10E9/L] •Platelets < 75,000/mm3 [75 x 10E9/L] •Hemoglobin < 9.0 g/dL •Total bilirubin > 1.5x ULN •AST/SGOT and ALT/SGPT > 2.5x ULN (AST and ALT > 5x ULN in the presence of liver metastases) •Serum creatinine > ULN and/or calculated
or measured creatinine clearance < 75% LLN •Inorganic phosphorus outside of normal limits •Total and ionized serum calcium outside of normal limits
Other protocol defined criteria may apply |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Overall response rate (ORR) is defined as the proportion of patients with a best overall response of Complete Response (CR) or Partial Response (PR), as
per RECIST version 1.1. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Baseline, then every 8 weeks, until disease progression or study discontinuation |
|
E.5.2 | Secondary end point(s) |
1- Overall survival
2- Progression free survival
3- Best overall response
4- Disease control rate
5- Number of participants with adverse events (AEs) and serious adverse events (SAEs) as a measure of safety and tolerability
6-Selected trough and 2-hr Plasma concentration profile |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
1- Every 4 months for one year after discontinuation of study treatment
2- Baseline, then every 8 weeks until disease progression or the initiation of subsequent anticancer therapies or death whichever occurs first
3- Baseline, then every 8 weeks, until disease progression or study discontinuation
4- Baseline, then every 8 weeks, until disease progression or study discontinuation
5- Starting from date of signing the consent form to 30 days afer the last
dose
6- From First dose of study treatment
to study discontinuation |
|
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 | Yes |
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) | 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 | 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 | 1 |
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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 4 |
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 |
Belgium |
France |
Germany |
Italy |
Japan |
Korea, Republic of |
Russian Federation |
Singapore |
Spain |
Taiwan |
Thailand |
Turkey |
United Kingdom |
United States |
|
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
|
End of study is defined as the time when the last patient completes the survival follow-up as described in the protocol or when the last patient on study has expired, been lost to follow up, or withdraws consent, whichever occurs first or when the study is terminated early. |
|
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 | 0 |
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 |
E.8.9.2 | In all countries concerned by the trial days | 0 |