Safety and efficacy study of RO5424802 in patients with non-small cell lung cancer with ALK mutation that did not respond or stop responding to crizotinib.

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 130

Inclusion Criteria

1.Patients with locally advanced (AJCC stage IIIB) not amenable to curative therapy) or metastatic AJCC stage IV
2.NSCLC2.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 0>2
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. Patients need to have a minimum 1-week wash-out period between the last dose of crizotinib and the first dose of study treatment (for patients enrolled in the midazolam substudy). Patients can either be chemotherapynaïve or have received at least one line of platinum-based chemotherapy for locally advanced or metastatic disease
8- Specific Inclusion Criteria Specific to Midazolam DDI Substudy Patients
· Patients with measurable or non-measurable disease
· Patients will require a minimum 2-week washout from crizotinib or other tyrosine kinase inhibitor prior to the dose of midazolam on Day -1
· Liver function tests at baseline (AST, ALT, and bilirubin) within normal limits (WNL)
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 112
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 18

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 the first dose of study treatment. Patients who received crizotinib or other tyrosine kinase inhibitors need to have a minimum 1-week wash-out period before the first dose of study treatment
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.
8 Specific Exclusion Criteria Specific to Midazolam DDI Substudy Patients
· Patients without a minimum of 2-week washout from crizotinib or other tyrosine kinase inhibitor prior to the dose of midazolam on Day -1
· History of hypersensitivity to midazolam or benzodiazepines or any contraindications to midazolam use including acute narrow angle glaucoma, myasthenia gravis, sleep apnea syndrome, etc. (see midazolam prescribing information: Roxane Laboratorie, 2007)
· Consumption of any CYP3A modulating agents including herbal supplements or foods (e.g. grapefruit, pomelo, star fruit or Seville orange containing products) within 2 weeks or 5 half-lives (whichever is longer) before the first dose of midazolam treatment and during the evaluation of the DDI (at least up to Day 22 of Cycle 1)
· Consumption of any concomitant medication with a reported serious drug interaction or which is contraindicated with midazolam within 2 weeks or 5 half-lives (whichever is longer) before the first dose of midazolam

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

Updated 10/9/2017

Safety and efficacy study of RO5424802 in patients with non-small cell lung cancer with ALK mutation that did not respond or stop responding to crizotinib.

Recruitment & Eligibility

Study & Design

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