AN OPEN-LABEL, NON-RANDOMIZED, MULTICENTER PHASE I/II TRIAL OF RO5424802 GIVEN ORALLY TO NON - SMALL CELL LUNG CANCER PATIENTS WHO HAVE ALK MUTATION AND FAILED CRIZOTINIB TREATMENT
- Conditions
- Non-Small Cell Lung Cancerlung cancer10038667
- Registration Number
- NL-OMON43709
- Lead Sponsor
- Hoffmann-La Roche
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 4
-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.;The midazolam sub-study was included into the main NP28673 protocol, this drug-drug interaction sub-study will only run in a very limited number of countries. The midazolam sub-study will not run in the Netherlands. Therefore new criteria not applicable.
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;The midazolam sub-study was included into the main NP28673 protocol, this drug-drug interaction sub-study will only run in a very limited number of countries. The midazolam sub-study will not run in the Netherlands. Therefore new criteria not applicable.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Part 1<br /><br>1. Determination of a Phase II recommended dose<br /><br>2. Incidence of DLTs by NCI CTCAE v4.03 grade and associated dose of<br /><br>RO5424802 (600 and 900 mg twice a day [BID])<br /><br>3. Plasma PK analysis for RO5424802<br /><br><br /><br>Part 2<br /><br>4. Objective tumor response rate (ORR) (Partial response [PR] and<br /><br>Complete response [CR]) as assessed by an independent radiological<br /><br>review committee using RECIST v1.1</p><br>
- Secondary Outcome Measures
Name Time Method <p>1. ORR (PR and CR) as assessed by IRC using RECIST v1.1 in subjects without<br /><br>prior exposure of cytotoxic chemotherapy treatment(s)<br /><br>2. ORR (PR and CR) as assessed by the investigator using RECIST v1.1<br /><br>3. Disease control rate based on IIRR<br /><br>4. Duration of Response based on IIRR<br /><br>5. Progression Free Survival based on IIRR<br /><br>6. CNS Objective Response Rate in subjects with measurable disease in the CNS<br /><br>metastasis as assessed by IRC<br /><br>7. Duration of CNS Response as assessed by IRC<br /><br>8. CNS progression rate as assessed by IRC<br /><br>9. Overall Survival</p><br>