E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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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 | 19.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10073071 |
E.1.2 | Term | Hepatocellular carcinoma |
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 |
Determine the recommended phase II dose (RP2D) of MSC2156119J.
Evaluate efficacy of MSC2156119J in subjects with MET+ advanced HCC pretreated with sorafenib and
Child Pugh class A liver function.
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E.2.2 | Secondary objectives of the trial |
Characterize the single and multiple dose pharmacokinetics (PK) of MSC2156119J.
Assess antitumor activity and biochemical response of MSC2156119J.
Evaluate safety and tolerability of MSC2156119J.
Evaluate the safety and tolerability of MSC2156119J.
Evaluate antitumor activity and biochemical response of MSC2156119J |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Histologically or cytologically confirmed HCC;
2. Child Pugh Class A liver function score;
3. For phase II only: MET+ status
4. Male or female, 18 years of age or older;
5. Measurable disease in accordance with RECIST Version 1.1;
6. Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1
(inclusive);
7. Previously treated with sorafenib for ≥ 4 weeks and discontinued sorafenib treatment
at least 14 days prior to Day 1 due to either intolerance or radiographic progression;
8. Signed and dated informed consent indicating that the subject (or legally acceptable
representative if applicable by local laws) has been informed of all the pertinent
aspects of the trial prior to enrollment;
9. Willingness and ability to comply with scheduled visits, treatment plans, laboratory
tests and other trial procedures; and
10. Life expectancy of at least 3 months as judged by the investigator. |
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E.4 | Principal exclusion criteria |
1. Prior systemic anticancer treatment for advanced HCC (except for sorafenib as
described in the inclusion criteria);
2. Prior treatment with any agent targeting the HGF/c-Met pathway;
3. Local-regional therapy within 4 weeks before Day 1
4. Impaired cardiac function
5. Additional exclusion criteria could apply. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Phase Ib: Number of DLTs occuring in Cycle 1
Phase II: Progression-free survival (PFS) status at 12 weeks |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
- Time to Progression according to RECIST v. 1.1
-Progression free survival according to RECIST v. 1.1 and mRECIST for HCC
-Time-to-symptomatic progression according to RECIST v. 1.1
-Overall survival
-Best overall response rate
-Disease control rate
-Biological response rate
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | Yes |
E.7.1.3.1 | Other trial type description |
• To determine the recommended phase II dose (RP2D) of MSC2156119J |
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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 | 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 | 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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 20 |
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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The end of the trial will be defined as 12 months after the last subject’s first dose of MSC2156119J. Subjects who are on active treatment with MSC2156119J at the time of end of the trial will be offered further treatment with MSC2156119J and assessments will be made as appropriate to determine whether a potential benefit from further treatment is seen. |
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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 | 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 |