This trial is active, not recruiting.

Condition non-squamous non-small cell lung cancer
Treatments erlotinib [tarceva], ro5452802
Phase phase 2
Targets EGFR, ALK
Sponsor Hoffmann-La Roche
Start date June 2013
End date January 2016
Trial size 154 participants
Trial identifier NCT01801111, 2012-004455-36, NP28673


This open-label, non-randomized, multicenter phase I/II study will evaluate the safety and efficacy of RO5424802 in patients with non-small cell lung cancer who have ALK mutation and failed crizotinib treatment. In Part 1, cohorts of patients will receive escalating doses of RO5424802 orally twice daily. In Part 2, patients will receive the recommended phase II dose of RO5424802 as determined in Part 1. Treatment will continue in Part 1 and Part 2 on the same dose until disease progression. In Part 3, following disease progression, patients without EGFR mutation will be offered continued treatment with RO5424802, patients with EGFR mutations will be offered a combination of RO5424802 and Tarceva (erlotinib).

United States No locations recruiting
Other countries No locations recruiting

Study Design

Allocation non-randomized
Endpoint classification safety/efficacy study
Intervention model single group assignment
Masking open label
Primary purpose treatment
erlotinib [tarceva]
Post progression: Continued treatment with RO542802 after disease progression will be in combination with Tarceva (100 mg orally daily) in patients with EGFR mutations
multiple oral doses

Primary Outcomes

Part 1: Determination of Phase II Recommended Dose
time frame: approximately 24 months
Part 1: Incidence of dose-limiting toxicities (DLTs) by NCI CTCAE v4.03 grade and associated dose of RO5424802
time frame: approximately 24 months
Part 2: Objective response rate (ORR) assessed by independent radiological review committee (IRC) using RECIST v1.1 in patients with and without prior exposure to cytotoxic chemotherapy treatment(s)
time frame: approximately 24 months
Safety: Incidence of adverse events
time frame: approximately 24 months
Pharmacokinetics: Area under the concentration-time curve (AUC)
time frame: 21 days

Secondary Outcomes

Objective response rate (ORR) per investigator review of radiographs using RECIST v1.1
time frame: approximately 24 months
Disease control rate, defined as percentage of patients with partial or complete response or stable disease for at least 16 weeks
time frame: approximately 24 months
Duration of objective response, defined as time from first observation of an objective tumor response to disease progression or death of any cause
time frame: approximately 24 months
Progression-free survival, defined as time from first RO5424802 treatment to disease progression or death from any cause
time frame: approximately 24 months
Central nervous System (CNS) response rate in patients with known CNS lesions who did not receive prior CNS radiation therapy
time frame: approximately 24 months
CNS progressive disease rate
time frame: approximately 24 months
Overall survival, defined as time from treatment initiation to death of any cause
time frame: approximately 24 months

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion Criteria: - Adult patients, >/= 18 years of age - Locally advanced or metastatic non-small cell lung cancer (stage IIIB or IV by AJCC 7th) - Eastern Cooperative Oncology Group (ECOG) performance status 0-2 - Documented ALK rearrangement based on FDA approved test - Prior treatment with crizotinib and progression according to RECIST v1.1 criteria with the last dose of crizotinib within 60 days from enrolment; patients can either be chemotherapy-naïve or have received at least one line of platinum-based chemotherapy - Adequate hematologic, hepatic and renal function - Patients with brain or leptomeningeal metastases are allowed on study if the lesions are asymptomatic without neurological signs and clinically stable for at least 2 weeks - Measurable disease according to RECIST v1.1 prior to administration of study drug Exclusion Criteria: - Receipt of any other ALK inhibitors in addition to crizotinib - Receipt of any prior cytotoxic chemotherapy for ALK-positive NSCLC within 4 weeks prior to Day 1. Patients who received crizotinib or any other tyrosine kinase inhibitors need to have a minimum 2-week washout period before the first dose - Active uncontrolled infectious diseases requiring treatment - NCI CTCAE (version 4.03) Grade 3 or higher toxicities due to prior therapy that have not shown improvement and are considered to interfere with current study medication - History of organ transplant - Co-administration of anti-cancer therapies other than those administered in this study - Baseline QTc > 470 ms or baseline symptomatic bradycardia < 45 beats per minute - Pregnant or breastfeeding women - Known HIV positivity or AIDS-related illness - History of significant drug-related allergy (such as anaphylaxis) - Any clinically significant concomitant disease or condition that could interfere with, or for which treatment might interfere with, the conduct of the study, or absorption of oral medications, or that would, in the opinion of the principal investigator, pose an unacceptable risk to the subject in the study

Additional Information

Trial information was received from ClinicalTrials.gov and was last updated in June 2015.
Information provided to ClinicalTrials.gov by Hoffmann-La Roche.
Location data was received from the National Cancer Institute and was last updated in April 2016.