E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Advanced solid tumors and hematological malignancies with ALK genetic alteration and/or overexpression |
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E.1.1.1 | Medical condition in easily understood language |
Specific tumors that are characterized by ALK genetic alteration (and/or overexpression in some diseases) |
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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 | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To assess the antitumor activity of ceritinib as measured by DCR determined by investigators |
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E.2.2 | Secondary objectives of the trial |
- To assess the antitumor activity of ceritinib as measured by ORR, DOR, TTR as determined by investigators
- To assess the antitumor activity of ceritinib as measured by PFS determined by investigators
- To assess the safety and tolerability of ceritinib. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Written informed consent for the main study obtained prior to any screening procedure.
- Patient must provide an archival or fresh tumor tissue before the first dose of the study drug for ALK testing at a Novartis designated central laboratory by a comparative technology: the confirmation of ALK positivity is not required for enrollment if other inclusion and exclusion criteria are fulfilled
- Patient is 18 years or older at the time of informed consent.
- Patient has WHO performance status ≤ 2.
- Patient has at least one measurable lesion as defined by appropriate guidelines. A lesion at a previously irradiated site may only be counted as a target lesion if there is clear sign of progression since the irradiation
Other protocol related inclusion criteria may apply |
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E.4 | Principal exclusion criteria |
1. Patient with ALK+ lung cancer.
2. Patient with known hypersensitivity to any of the excipients of LDK378.
3. Patient with symptomatic CNS metastases who are neurologically unstable or have required increasing doses of steroids within the 2 weeks prior to study entry to manage CNS symptoms.
4. History of carcinomatous meningitis.
5. Patient with diarrhea CTCAE ≥ grade 2; or patients with neuropathy CTCAE ≥ grade 2
Other protocol related exclusion criteria may apply. |
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E.5 End points |
E.5.1 | Primary end point(s) |
DCR, defined as the proportion of patients with best overall response of CR, PR, or SD ≥ 16 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) |
1. ORR, defined as the proportion of patients with a best overall response defined as CR or PR; (CR+PR)
2. The following endpoints will be evaluated by investigator assessment :
– DOR, defined as the time from date of first documented CR or PR to date of first documented disease progression or death due to any cause
- TTR, defined as the time from date of the first dose to date of first documented response (CR or PR)
– PFS, defined as time from date of the first dose to date of first documented disease progression or date of death due to any cause
3. ECG, Performance status, Vital signs, Physical examination; AEs, and laboratory (hematology, biochemistry, urinalysis, coagulation, pregnancy test and hormones (males only)
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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 | Yes |
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 | 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 | 5 |
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 | 15 |
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 |
Argentina |
Belgium |
Czech Republic |
France |
Germany |
Israel |
Korea, Republic of |
Netherlands |
Thailand |
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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
|
The study will end approximately 38 weeks after the last patient treated in the study or once at least 75% of patients have died or have been lost to follow-up.
Novartis may continue to supply ceritinib to patients who may benefit from continued treatment as per the Investigator’s opinion. |
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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 | 40 |
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 | 9 |