Safety and efficacy study of RO5424802 in subjects with non-small cell lung cancer with ALK mutation that did not respond or stop responding to crizotinib.
- Conditions
- ALK positive Non-Small cell lung cancerMedDRA version: 19.0Level: PTClassification code 10061873Term: Non-small cell lung cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2012-004455-36-NL
- Lead Sponsor
- F. Hoffmann-La Roche Ltd
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 138
-Patients with locally advanced (AJCC stage IIIB) not amenable to curative therapy or metastatic (AJCC stage IV) NSCLC
-Male or female =18 years old
-Life expectancy, in the opinion of the investigator, of at least 12 weeks
-Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2
-Histologically confirmed NSCLC
-Documented ALK rearrangement based on a Food and Drug Administration (FDA) approved test
-Prior treatment with crizotinib and progression based on RECIST criteria version 1.1. Subjects 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). Subjects can either be chemotherapynaïve or have received at least one line of
platinum-based chemotherapy for locally advanced or metastatic disease
-Adequate hematologic function
-Adequate hepatic function
-Adequate renal function
-Recovery from effects of any major surgery or significant traumatic injury at least 28 days before the first dose of study treatment
-Subjects with brain or leptomeningeal metastases are allowed on study if they have previously been treated with Whole brain radiotherapy (WBRT) or gamma-knife radiosurgery. Subjects must have completed treatment, be clinically stable and have discontinued the use of corticosteroids for this indication for>=2 weeks. If not previously treated with WBRT or gamma-knife radiosurgery, subjects must have been asymptomatic without neurological signs and clinically stable for >=2 weeks without steroid treatment prior to first dose
-Measurable disease (by RECIST criteria version 1.1) prior to the first dose of study treatment
-Negative pregnancy test within 10 days of first dose for women of child bearing potential
-For women of childbearing potential: agreement to remain abstinent or use contraceptive methods that result in a failure rate of < 1% per year during the treatment period and for at least 3 months after the last dose of study drug
-For men: agreement to use a barrier method of contraception during the treatment period and for at least 3 months after the last dose
Specific Inclusion Criteria Specific to Midazolam DDI Substudy subjects
-Subjects with measurable or non-measurable disease
-Subjects 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
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.National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (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. Baseline QTc >470 ms, or baseline symptomatic bradycardia <45 beats per minute
9. Known HIV positivity or AIDS-related illness
10. Any significant concomitant disease
11. Administration of strong/ potent CYP3A inhibitors or inducers within 14 days prior to first administration of study drug
12. History of hypersensitivity to any of the additives in the RO5424802 formulation
13. Any clinically significant concomitant disease
14. Any psychological, familial, sociological or geographical condition
Specific Exclusion Criteria Specific to Midazolam DDI Substudy Subjects
· 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