E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
non-squamous non-small cell lung cancer (NSCLC) |
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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 | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10061873 |
E.1.2 | Term | Non-small cell lung cancer |
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 |
To compare the antitumor activity of LDK378 versus reference chemotherapy, as measured by PFS determined by a BIRC |
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E.2.2 | Secondary objectives of the trial |
Key secondary:
- To compare OS in patients treated with LDK378 versus reference chemotherapy
Other secondary:
1. To assess the antitumor activity of LDK378 versus reference chemotherapy, as measured by ORR, DOR, DCR, and TTR determined by BIRC and by investigators
2. To assess the antitumor activity of LDK378 versus reference chemotherapy, as measured by PFS determined by investigators
3. To evaluate the safety profile of LDK378 versus reference chemotherapy
4. To assess the effect of LDK378 versus reference chemotherapy on PROs, including disease related symptoms, functioning, and health-related quality of life
5. To characterize the PK of LDK378 in this patient population
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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: Complementary study of assessment of biomarker included in the original protocol "A phase III multicenter, randomized study of oral LDK378 versus standard chemotherapy in previously untreated adult patients with ALK rearranged (ALK-positive), stage IIIB or IV, non-squamous non-small cell lung cancer." Version: 00
Date: 21-03-2013 Objectives: To determine changes in genes and proteins to better understand how LDK378 acts on the body and the tumor. Therefore the purpose of this additional study is to investigate the mechanism of action of the drug and its activity and / or to the tumor.
Title: Complementary study of extensive ECG evaluation that includes additional pharmacokinetics sampling included in the original protocol "A phase III multicenter, randomized study of oral LDK378 versus standard chemotherapy in previously untreated adult patients with ALK rearranged (ALK-positive), stage IIIB or IV, non-squamous non-small cell lung cancer." Version: 00
Date: 21-03-2013 Objectives: This additional study has two purposes: 1. Compare the effect on cardiac activity in patients taking LDK378 than cardiac activity in patients taking standard chemotherapy (pemetrexed in combination with cisplatin or carboplatin) 2. Evaluate the safety in use of LDK378 by measuring the concentrations of LDK378 in blood and correlating these concentrations to heart activity recorded at the same time. |
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E.3 | Principal inclusion criteria |
1. Patient has a histologically or cytologically confirmed diagnosis of non-squamous NSCLC that is ALK positive as assessed by the Ventana IHC test. The test will be performed at Novartis designated central laboratories.
2. Patient has newly diagnosed stage IIIB or IV NSCLC or relapsed locally advanced or metastatic NSCLC not previously treated with any systemic anti-cancer therapy (e.g. cytotoxic drugs, monoclonal antibody therapy, crizotinib or other ALK inhibitors, or other targeted therapies, either experimental or not), with exception of neo-adjuvant or adjuvant therapy as depicted in criterion 6. (For AJCC stage groupings and TNM definitions, refer to NCI 2012 guidelines)
3. Patient has at least one measurable lesion as defined by RECIST 1.1. A previously irradiated site lesion may only be counted as a target lesion if there is clear sign of progression since the irradiation.
Other protocol-defined inclusion criteria may apply |
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E.4 | Principal exclusion criteria |
1. Patient with known hypersensitivity to any of the excipients of LDK378 (microcrystalline cellulose, mannitol, crospovidone, colloidal silicon dioxide and magnesium stearate)
2. Patient with a history of severe hypersensitivity reaction to platinum containing drugs, pemetrexed or any known excipients of these drugs.
3. Patient with symptomatic CNS metastases who is neurologically unstable or has required increasing doses of steroids within the 2 weeks prior to screening to manage CNS symptoms.
Other protocol-defined exclusion criteria may apply
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E.5 End points |
E.5.1 | Primary end point(s) |
progression free survival (PFS), defined as time from date of randomization to date of first documented disease progression (as assessed by BIRC per RECIST 1.1) or date of death due to any cause |
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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) |
key secondary:
- overall survival (OS), defined as time from date of randomization to date of death due to any cause
other secondary:
1. The following endpoints will be evaluated by BIRC and by investigator assessment per RECIST 1.1:
– a ORR, defined as the proportion of patients with a best overall response defined as CR or PR; (CR+PR)
– b DOR, defined as the time from date of first documented CR or PR to date of first documented disease progression or death due to underlying cancer
– c DCR, defined as the proportion of patients with best overall response of CR, PR, or SD
– d TTR, defined as the time from date of randomization to date of first documented response (CR or PR)
Other secondary endpoints as per full protocol may apply |
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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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
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 | Yes |
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.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 21 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 130 |
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 |
Austria |
Belgium |
Brazil |
Canada |
China |
Colombia |
Denmark |
Finland |
France |
Germany |
Greece |
Hungary |
India |
Italy |
Japan |
Korea, Republic of |
Lebanon |
Netherlands |
Norway |
Peru |
Poland |
Russian Federation |
Singapore |
Spain |
Sweden |
Taiwan |
Thailand |
Turkey |
United Kingdom |
United States |
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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 study will end once the final OS analysis is performed (see Section 10.5.1 of the protocol). Patients deriving benefit from treatment will be enrolled in a separate protocol. |
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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 | 1 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |