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.

• Register: EUCTR
• Last refreshed on: 23 October 2017
• Main ID: EUCTR2012-004455-36-BE
• Date of registration: 03/04/2013
• Prospective Registration: Yes
• Primary sponsor: F.Hoffmann-La Roche Ltd
• Public title: 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.
• Scientific title: 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
• Date of first enrolment: 31/05/2013
• Target sample size: 130
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2012-004455-36
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): yes Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Australia, Belgium, Denmark, France, Germany, Hong Kong, Italy, Luxembourg, Netherlands, Russian Federation, Singapore, Spain, Sweden, Taiwan, United Kingdom, United States

Contacts

• Name: Trial Information Support Line-TISL
• Affiliation: F. Hoffmann-La Roche Ltd

• Name: Trial Information Support Line-TISL
• Affiliation: F. Hoffmann-La Roche Ltd

Key inclusion & exclusion criteria

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


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

ALK-mutated Non-small cell lung cancer
MedDRA version: 16.1 Level: PT Classification code 10061873 Term: Non-small cell lung cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Therapeutic area: Diseases [C] - Cancer [C04]

Intervention(s)

Product Name: ALK Inhibitor
Product Code: RO5424802
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Alectinib
Current Sponsor code: RO5424802/F03
Other descriptive name: ALK Inhibitor
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 150-

Trade Name: Tarceva
Product Name: Tarceva
Product Code: RO0508231/V05
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Erlotinib
CAS Number: 183321-74-6
Current Sponsor code: RO0508231/V05
Other descriptive name: erlotinib hydrochloride
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 25-

Trade Name: Tarceva
Product Name: Tarceva
Product Code: RO0508231/V02
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: ERLOTINIB
CAS Number: 183321-74-6
Current Sponsor code: RO05508231/V02
Other descriptive name: erlotinib hydrochloride
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-

Trade Name: Tarceva
Product Name: Tarceva
Product Code: RO0508231/V03
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: ERLOTINIB
CAS Number: 183321-74-6
Current Sponsor code: RO0508231/V03
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 150-

Primary Outcome(s)

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

Main Objective: The primary objectives for Part 1 of the study are as follows:
-To determine the RP2D of RO5424802 to be used in Part 2 of the study
-To evaluate the safety and tolerability of 600-mg and 900-mg doses of RO5424802 administered twice daily to patients with locally advanced or metastatic NSCLC who have ALK rearrangement and in whom prior crizotinib therapy has failed
-To characterize DLTs, if any, associated with RO5424802 after 21 days of
treatment when administered twice daily at 600- and 900-mg doses to patients with locally advanced or metastatic NSCLC who have ALK re-arrangement and in whom prior crizotinib therapy has failed
-To characterize the 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.

Timepoint(s) of evaluation of this end point: Please refer to E.5.1

Secondary Objective: •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

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Please refer to 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

Secondary ID(s)

NP28673

2012-004455-36-SE

Source(s) of Monetary Support

F. Hoffmann-La Roche Ltd