E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Advanced stage RET-rearranged NSCLC |
|
E.1.1.1 | Medical condition in easily understood language |
Lung cancer called "non-small cell lung cancer (NSCLC)" that has spread to other parts of the Body (metastatic) and that has a rearrangment in the RET gene |
|
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 | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10029522 |
E.1.2 | Term | Non-small cell lung cancer stage IV |
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 | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To assess the efficacy of alectinib in terms of best overall response (OR) assessed by RECIST 1.1. |
|
E.2.2 | Secondary objectives of the trial |
The secondary objectives are to evaluate secondary measures
of clinical efficacy including disease control, progression-free survival (PFS), and overall survival (OS) as well as to assess safety and tolerability of the treatment and to describe the
association of primary and secondary outcomes with tumour characteristics. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Histologically or cytologically-documented non-small cell lung carcinoma
- Advanced disease defined as recurrent stage IV (according to 8th TNM classification) or recurrent or progressive disease following multimodal therapy (radiation therapy, surgical
resection, or definitive chemo-radiation therapy for locally advanced disease)
- RET rearrangement detected by FISH, Nanostring or by parallel-sequencing on FFPE tumour tissue (biopsy, resection or cytoblock) assessed locally.
- Availability of FFPE tumour material for central confirmation of RET-rearrangement
- At least one prior platinum-based systemic regimen: Adjuvant or neoadjuvant or definitive platinum-based chemo-radiotherapy treatments are considered as a line of treatment only if completed less than 6 months before enrolment. Maintenance therapy following platinum doublet-based chemotherapy is not considered a separate regimen of therapy.
- Measurable or non-measurable, but radiologically evaluable (except for skin lesions) disease according to RECIST v1.1 criteria
- Adequate haematological, renal and liver function
- ECOG Performance Status 0-2 |
|
E.4 | Principal exclusion criteria |
- Untreated, active CNS metastases
- Carcinomatous meningitis
- Baseline symptomatic bradycardia
- Prior treatment with any RET TKI or RET targeted therapy
- Known EGFR, ALK, ROS, and BRAF mutation (in addition to RET rearrangement)
- Any GI disorder that may affect absorption of oral medications, such as malabsorption syndrome or status post-major bowel resection
- History of hypersensitivity to any of the additives in the alectinib drug formulation
- Pregnant or lactating women
- Known HIV positivity or AIDS-related illness
- Any concurrent systemic anticancer therapy
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
Best overall response (OR = CR or PR), per investigator assessment, according to RECIST 1.1. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
from the start of trial treatment across all time points until the end of trial
treatment. |
|
E.5.2 | Secondary end point(s) |
-Best Overall (OR) response per independent review
-Disease control (DC): best overall response of CR or PR, or SD (or non-CR/non-PD in the case of non-measurable disease only)
-Progression-free survival (PFS)
-Overall survival (OS)
-Safety and tolerability |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
-OR: from the start of trial treatment across all time points until the end of trial Treatment
-DC: measured at 24 weeks
-PFS: time from the date of enrolment until documented progression or death, if progression is not documented
-OS: time from the date of enrolment until death from any cause
-Safety and tolerability: from the date of signature of informed consent until 30 days after all trial treatment discontinuation, regardless of whether it is considered related to a medication |
|
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 | No |
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 | Yes |
E.8.1.7.1 | Other trial design description |
|
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.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 23 |
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 |
Ireland |
Italy |
Netherlands |
Portugal |
Slovenia |
Spain |
Switzerland |
|
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
|
The trial ends when both of the following criteria are satisfied:
- The trial is mature for the analysis of the primary endpoint, according to protocol specifications.
- The cleaning procedure of the database is completed and database is ‘frozen’.
The total duration of the trial is expected to be 5 years, including a run-in period of 6 months and an additional 6 months for the final analysis report. |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 5 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 5 |