E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
ALK-mutated Non-small cell lung cancer |
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E.1.1.1 | Medical condition in easily understood language |
ALK-mutated Non-small cell lung cancer |
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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 |
The primary objectives for Part 1 of the study are as follows:
To determine the recommended Phase II dose (RP2D) of RO5424802 to be used in Part 2 of the study
• To evaluate the safety and tolerability of 600-mg and 900-mg (if 900 mg is reached) doses of RO5424802 administered twice-daily for 21 days to patients with locally advanced or metastatic NSCLC (stage IIIb or stage IV) who have anaplastic lymphoma kinase (ALK) re-arrangement and in whom prior crizotinib therapy has failed
• To characterize the pharmacokinetics (PK) of RO5424802
The primary efficacy objectives for Part 2 study are as follows:
•To evaluate efficacy of RO5424802 by objective response rate (ORR) as per central independent radiological review committee (IRC) using RECIST criteria version 1.1 in the overall population [with and without prior exposure of cytotoxic chemotherapy treatment(s)].
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E.2.2 | Secondary objectives of the trial |
•To evaluate efficacy of RO5424802 by objective response rate (ORR) as
per central IRC using RECIST criteria version 1.1 in patients without
prior exposure of cytotoxic chemotherapy treatment(s)
•To evaluate efficacy of RO5424802 by ORR per investigator review of
radiographs using RECIST 1.1
•To evaluate disease control rate (DCR) of RO5424802 based on IRC and
investigator review of radiographs |
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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 |
The Roche Clinical Repository (RCR) is a centrally administered group of facilities for
the long-term storage of human biologic specimens, including body fluids, solid tissues, and derivatives thereof (e.g., DNA, RNA, proteins, peptides). The collection and analysis of RCR specimens will facilitate the rational design of new pharmaceutical agents and the development of diagnostic tests, which may allow for individualized drug
therapy for patients in the future. Specimens for the RCR will be collected from patients who give specific consent to
participate in this optional research.
Protocol version : see section A (part of the main protocol) |
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E.3 | Principal inclusion criteria |
1.Patients with locally advanced or metastatic NSCLC (stage IIIB or stage IV by AJCC 7th)
2.Male or female ≥18 years old
3.Life expectancy, in the opinion of the investigator, of at least 12 weeks
4.ECOG Performance Status of 02
5.Histologically confirmed NSCLC
6.Documented ALK rearrangement based on an FDA approved test
7.Prior treatment with crizotinib and progression based on RECIST criteria version 1.1 with the last dose of crizotinib being within 60 days from enrolment. Patients can either be chemotherapy-naïve or have received at least one line of platinum-based chemotherapy
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E.4 | Principal exclusion criteria |
1.Receipt of any other ALK inhibitors in addition to crizotinib
2.Receipt of any prior cytotoxic chemotherapy for ALK-positive NSCLC within 4 weeks prior to Day 1. Patients who received crizotinib or other tyrosine kinase inhibitors need to have a minimum 2-week wash-out period before the first dose
3.A previous malignancy within the past 3 years (other than curatively treated basal cell carcinoma of the skin, early gastrointestinal cancer by endoscopic resection, in situ carcinoma of the cervix or any cured cancer that is considered to have no impact on PFS and OS for the current NSCLC)
4.Active or uncontrolled infectious diseases requiring treatment
5.NCI CTCAE (version 4.03) Grade 3 or higher toxicities due to prior therapy that has not shown improvement and are considered to interfere with current study medication.
6.History of organ transplant
7.Co-administration of anti-cancer therapies other than those administered in this study.
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E.5 End points |
E.5.1 | Primary end point(s) |
Part 1 – Determination of a Phase II recommended dose – Dose Escalation Study
•Incidence of DLTs by NCI CTCAE v4.03 grade and associated dose of RO5424802 (600 and 900 mg BID)
Part 2 – Evaluation of Safety and Efficacy of RO5424802 in ALK-positive NSCLC Patients with ALK Rearrangements.
•Objective tumor response rate (PR and CR) as assessed by an independent radiological review committee using RECIST v1.1
•Objective responses must be confirmed ≥28 days after initial response; [Primary in the “all patients” and “patients who have received at least one line of platinum-based cytotoxic chemotherapy” groups |
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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) |
• To evaluate efficacy of RO5424802 by ORR per investigator review of radiographs using RECIST 1.1
• To evaluate disease control rate (DCR) of RO5424802 based on IRC and investigator review of radiographs
• To assess duration of response (DOR) in patients treated with RO5424802 based on IRC and investigator review of radiographs
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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 | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
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) | 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 |
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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 | Information not present in EudraCT |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
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 | 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 | 13 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 30 |
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 |
Australia |
Canada |
France |
Germany |
Italy |
Netherlands |
Russian Federation |
Spain |
United Kingdom |
United States |
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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
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The end of the study is defined as the date when the last patient, last visit (LPLV) occurs. As patients will be offered continued treatment beyond progression with RO5424802 alone or in combination with erlotinib depending on their EGFR status and whether the treating physicians consider that the patient is still benefiting from RO5424802 treatment, LPLV is expected to occur when the last patient has either died or is lost to follow-up.
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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 |