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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01801111




Registration number
NCT01801111
Ethics application status
Date submitted
20/02/2013
Date registered
28/02/2013
Date last updated
2/11/2018

Titles & IDs
Public title
A Study of Alectinib (RO5424802) in Participants With Non-Small Cell Lung Cancer Who Have Anaplastic Lymphoma Kinase (ALK) Mutation and Failed Crizotinib Treatment
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 Who Have Failed Crizotinib Treatment
Secondary ID [1] 0 0
2012-004455-36
Secondary ID [2] 0 0
NP28673
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Non-Small-Cell Lung Carcinoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lung - Non small cell

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Erlotinib
Treatment: Drugs - Alectinib

Experimental: Alectinib - Participants will receive alectinib treatment continuously starting from Day 1 Cycle 1 (in 28-day cycles) until disease progression, death, or withdrawal for any other reasons, whichever occurs first. After PD, participants without EGFR mutation will continue treatment with alectinib alone and participants with EGFR mutation will receive alectinib in combination with erlotinib as per discretion of the treating physician.


Treatment: Drugs: Erlotinib
Erlotinib will be administered at a dose of 100 mg via tablet, orally, once daily in combination with alectinib to participants who progressed on alectinib alone treatment as per treating physician discretion.

Treatment: Drugs: Alectinib
Alectinib will be administered at a dose of 600 milligrams (mg) via capsule, orally, twice daily.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Recommended Phase 2 Dose (RP2D) of Alectinib
Timepoint [1] 0 0
Cycle 1 (up to 28 days)
Primary outcome [2] 0 0
Percentage of Participants With Dose Limiting Toxicities (DLTs)
Timepoint [2] 0 0
Cycle 1 (up to 28 days)
Primary outcome [3] 0 0
Percentage of Participants Achieving Objective Response (Complete Response [CR] or Partial Response [PR]) as Assessed by Independent Radiological Review Committee (IRC) in Response Evaluable (RE) Population
Timepoint [3] 0 0
Baseline; assessments every 8 weeks post-baseline until progressive disease, unacceptable toxicity, consent withdrawal, death, other reason deemed by investigator, or last tumor assessment (up to approximately 2.5 years)
Primary outcome [4] 0 0
Percentage of Participants Achieving Objective Response (CR or PR) as Assessed by IRC in Chemotherapy-Pretreated Participants
Timepoint [4] 0 0
Baseline; assessments every 8 weeks post-baseline until progressive disease, unacceptable toxicity, consent withdrawal, death, other reason deemed by investigator, or last tumor assessment (up to approximately 2.5 years)
Secondary outcome [1] 0 0
Percentage of Participants Achieving Objective Response (CR or PR) as Assessed by IRC in Chemotherapy-Naive Participants
Timepoint [1] 0 0
Baseline; assessments every 8 weeks post-baseline until progressive disease, unacceptable toxicity, consent withdrawal, death, other reason deemed by investigator, or last tumor assessment (up to approximately 2.5 years)
Secondary outcome [2] 0 0
Percentage of Participants Achieving Objective Response (CR or PR) as Assessed by Investigator in RE Population
Timepoint [2] 0 0
Baseline; assessments every 8 weeks post-baseline until progressive disease, unacceptable toxicity, consent withdrawal, death, other reason deemed by investigator, or last tumor assessment (up to approximately 2.5 years)
Secondary outcome [3] 0 0
Percentage of Participants Achieving Objective Response (CR or PR) as Assessed by Investigator in Chemotherapy-Pretreated Participants
Timepoint [3] 0 0
Baseline; assessments every 8 weeks post-baseline until progressive disease, unacceptable toxicity, consent withdrawal, death, other reason deemed by investigator, or last tumor assessment (up to approximately 2.5 years)
Secondary outcome [4] 0 0
Percentage of Participants Achieving Objective Response (CR or PR) as Assessed by Investigator in Chemotherapy-Naive Participants
Timepoint [4] 0 0
Baseline; assessments every 8 weeks post-baseline until progressive disease, unacceptable toxicity, consent withdrawal, death, other reason deemed by investigator, or last tumor assessment (up to approximately 2.5 years)
Secondary outcome [5] 0 0
Duration of Response (DoR) as Assessed by IRC in RE Population
Timepoint [5] 0 0
Baseline; assessments every 8 weeks post-baseline until progressive disease, unacceptable toxicity, consent withdrawal, death, other reason deemed by investigator, or last tumor assessment (up to approximately 2.5 years)
Secondary outcome [6] 0 0
Percentage of Participants With PD as Assessed by IRC According to RECIST v1.1 or Death From Any Cause in Safety Population
Timepoint [6] 0 0
Baseline; assessments every 8 weeks post-baseline until progressive disease, unacceptable toxicity, consent withdrawal, death, other reason deemed by investigator, or last tumor assessment (up to approximately 2.5 years)
Secondary outcome [7] 0 0
Progression Free Survival (PFS) as Assessed by IRC in Safety Population
Timepoint [7] 0 0
Baseline; assessments every 8 weeks post-baseline until progressive disease, unacceptable toxicity, consent withdrawal, death, other reason deemed by investigator, or last tumor assessment (up to approximately 2.5 years)
Secondary outcome [8] 0 0
Percentage of Participants Who Died of Any Cause
Timepoint [8] 0 0
Baseline up to death from any cause (up to approximately 4 years)
Secondary outcome [9] 0 0
Overall Survival (OS)
Timepoint [9] 0 0
Baseline up to death from any cause (up to approximately 4 years)
Secondary outcome [10] 0 0
Percentage of Participants Achieving CR, PR or Stable Disease (SD) According to RECIST v1.1 in RE Population
Timepoint [10] 0 0
Baseline; assessments every 8 weeks post-baseline until progressive disease, unacceptable toxicity, consent withdrawal, death, other reason deemed by investigator, or last tumor assessment (up to approximately 2.5 years)
Secondary outcome [11] 0 0
Percentage of Participants Achieving Central Nervous System (CNS) Objective Response as Assessed by IRC According to RECIST v1.1
Timepoint [11] 0 0
Baseline; assessments every 8 weeks post-baseline until progressive disease, unacceptable toxicity, consent withdrawal, death, other reason deemed by investigator, or last tumor assessment (up to approximately 2.5 years)
Secondary outcome [12] 0 0
Percentage of Participants Achieving CNS Objective Response as Assessed by IRC According to Radiology Assessment in Neuro-Oncology (RANO) Criteria
Timepoint [12] 0 0
Baseline; assessments every 8 weeks post-baseline until progressive disease, unacceptable toxicity, consent withdrawal, death, other reason deemed by investigator; then survival follow-up until cutoff 18 August 2014 (up to approximately 53 weeks)
Secondary outcome [13] 0 0
CNS Duration of Response (CDoR) as Assessed by IRC According to RECIST v1.1
Timepoint [13] 0 0
Baseline; assessments every 8 weeks post-baseline until progressive disease, unacceptable toxicity, consent withdrawal, death, other reason deemed by investigator, or last tumor assessment (up to approximately 2.5 years)
Secondary outcome [14] 0 0
CDoR as Assessed by IRC According to RANO Criteria
Timepoint [14] 0 0
Baseline; assessments every 8 weeks post-baseline until progressive disease, unacceptable toxicity, consent withdrawal, death, other reason deemed by investigator; then survival follow-up until cutoff 18 August 2014 (up to approximately 53 weeks)
Secondary outcome [15] 0 0
Percentage of Participants With CNS Progression as Assessed by IRC According to RECIST v 1.1
Timepoint [15] 0 0
Baseline; assessments every 8 weeks post-baseline until progressive disease, unacceptable toxicity, consent withdrawal, death, other reason deemed by investigator; then survival follow-up until cutoff 18 August 2014 (up to approximately 53 weeks)
Secondary outcome [16] 0 0
Maximum Observed Plasma Concentration (Cmax) of Alectinib
Timepoint [16] 0 0
Pre-dose (0 hours [hrs]), and 0.5, 1, 2, 4, 6, 8, 10, 12 hrs post-dose on Day 1 and Day 21 of Cycle 1
Secondary outcome [17] 0 0
Time to Cmax (Tmax) of Alectinib
Timepoint [17] 0 0
Pre-dose (0 hrs), and 0.5, 1, 2, 4, 6, 8, 10, 12 hrs post-dose on Day 1 and Day 21 of Cycle 1
Secondary outcome [18] 0 0
Time to Last Measurable Plasma Concentration (Tlast) of Alectinib
Timepoint [18] 0 0
Pre-dose (0 hrs), and 0.5, 1, 2, 4, 6, 8, 10, 12 hrs post-dose on Day 1 and Day 21 of Cycle 1
Secondary outcome [19] 0 0
Area Under the Plasma Concentration-Time Curve From Time 0 to 10 Hours Post-dose (AUC[0-10]) of Alectinib
Timepoint [19] 0 0
Pre-dose (0 hrs), and 0.5, 1, 2, 4, 6, 8, 10, 12 hrs post-dose on Day 1 and Day 21 of Cycle 1
Secondary outcome [20] 0 0
Area Under the Plasma Concentration-Time Curve From Time 0 to Tlast (AUC[0-last]) of Alectinib
Timepoint [20] 0 0
Pre-dose (0 hrs), and 0.5, 1, 2, 4, 6, 8, 10, 12 hrs post-dose on Day 1 and Day 21 of Cycle 1
Secondary outcome [21] 0 0
Cmax of Alectinib Metabolite
Timepoint [21] 0 0
Pre-dose (0 hrs), and 0.5, 1, 2, 4, 6, 8, 10, 12 hrs post-dose on Day 1 and Day 21 of Cycle 1
Secondary outcome [22] 0 0
Tmax of Alectinib Metabolite
Timepoint [22] 0 0
Pre-dose (0 hrs), and 0.5, 1, 2, 4, 6, 8, 10, 12 hrs post-dose on Day 1 and Day 21 of Cycle 1
Secondary outcome [23] 0 0
Tlast of Alectinib Metabolite
Timepoint [23] 0 0
Pre-dose (0 hrs), and 0.5, 1, 2, 4, 6, 8, 10, 12 hrs post-dose on Day 1 and Day 21 of Cycle 1
Secondary outcome [24] 0 0
AUC(0-10) of Alectinib Metabolite
Timepoint [24] 0 0
Pre-dose (0 hrs), and 0.5, 1, 2, 4, 6, 8, 10, 12 hrs post-dose on Day 1 and Day 21 of Cycle 1
Secondary outcome [25] 0 0
AUC(0-last) of Alectinib Metabolite
Timepoint [25] 0 0
Pre-dose (0 hrs), and 0.5, 1, 2, 4, 6, 8, 10, 12 hrs post-dose on Day 1 and Day 21 of Cycle 1
Secondary outcome [26] 0 0
Metabolite to Parent Ratio Based on AUC(0-10)
Timepoint [26] 0 0
Pre-dose (0 hrs), and 0.5, 1, 2, 4, 6, 8, 10, 12 hrs post-dose on Day 1 and Day 21 of Cycle 1
Secondary outcome [27] 0 0
Metabolite to Parent Ratio Based on AUC(0-last)
Timepoint [27] 0 0
Pre-dose (0 hrs), and 0.5, 1, 2, 4, 6, 8, 10, 12 hrs post-dose on Day 1 and Day 21 of Cycle 1
Secondary outcome [28] 0 0
Trough Plasma Concentration (Ctrough) of Alectinib
Timepoint [28] 0 0
Pre-dose (0 hrs) on Day 21 of Cycle 1
Secondary outcome [29] 0 0
Ctrough of Alectinib Metabolite
Timepoint [29] 0 0
Pre-dose (0 hrs) on Day 21 of Cycle 1
Secondary outcome [30] 0 0
Peak to Trough Ratio of Alectinib
Timepoint [30] 0 0
Pre-dose (0 hrs), and 0.5, 1, 2, 4, 6, 8, 10, 12 hours post-dose on Day 21 of Cycle 1
Secondary outcome [31] 0 0
Accumulation Ratio of Alectinib
Timepoint [31] 0 0
Pre-dose (0 hrs), and 0.5, 1, 2, 4, 6, 8, 10, 12 hours post-dose on Day 1 and Day 21 of Cycle 1
Secondary outcome [32] 0 0
Accumulation Ratio of Alectinib Metabolite
Timepoint [32] 0 0
Pre-dose (0 hrs), and 0.5, 1, 2, 4, 6, 8, 10, 12 hours post-dose on Day 1 and Day 21 of Cycle 1

Eligibility
Key inclusion criteria
* Locally advanced or metastatic non-small cell lung cancer (stage IIIB or IV by American Joint Committee on Cancer [AJCC])
* Eastern Cooperative Oncology Group (ECOG) performance status 0-2
* Documented ALK rearrangement based on Food and Drug Administration (FDA)-approved test
* Prior treatment with crizotinib and progression according to response evaluation criteria in solid tumors version 1.1 (RECIST v1.1) criteria. Participants had to have a minimum 1-week wash-out period between the last dose of crizotinib and the first dose of study treatment. Participants can either be chemotherapy-naïve or have received at least one line of platinum-based chemotherapy
* Adequate hematologic, hepatic, and renal function
* Participants with brain or leptomeningeal metastases are allowed if protocol defined criteria are met
* Measurable disease according to RECIST v1.1 prior to administration of first dose of study drug
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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 the first dose of study drug
* Participants who received crizotinib or any other tyrosine kinase inhibitors need to have a minimum 1-week washout period before the first dose of study drug
* Active or uncontrolled infectious diseases requiring treatment
* National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03 (NCI CTCAE v4.03) 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 corrected Q-T interval (QTc) greater than (>) 470 milliseconds, or baseline symptomatic bradycardia (less than 45 heart beats per minute)
* Pregnant or breastfeeding women
* Known Human Immunodeficiency Virus (HIV) positivity or Acquired Immunodeficiency Syndrome (AIDS)-related illness
* History of hypersensitivity to any of the additives in the alectinib formulation
* 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 participant in the study

Study design
Purpose of the study
Treatment
Allocation to intervention
Not applicable
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
20/06/2013
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
27/10/2017
Sample size
Target
Accrual to date
Final
138
Recruitment in Australia
Recruitment state(s)
NSW,QLD
Recruitment hospital [1] 0 0
Royal North Shore Hospital - St. Leonards
Recruitment hospital [2] 0 0
Prince Charles Hospital - Chermside
Recruitment hospital [3] 0 0
Townsville General Hospital - Douglas
Recruitment postcode(s) [1] 0 0
2065 - St. Leonards
Recruitment postcode(s) [2] 0 0
4032 - Chermside
Recruitment postcode(s) [3] 0 0
4184 - Douglas
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Illinois
Country [5] 0 0
United States of America
State/province [5] 0 0
Missouri
Country [6] 0 0
United States of America
State/province [6] 0 0
Nevada
Country [7] 0 0
United States of America
State/province [7] 0 0
New York
Country [8] 0 0
United States of America
State/province [8] 0 0
Ohio
Country [9] 0 0
United States of America
State/province [9] 0 0
Texas
Country [10] 0 0
United States of America
State/province [10] 0 0
Virginia
Country [11] 0 0
Belgium
State/province [11] 0 0
Edegem
Country [12] 0 0
Belgium
State/province [12] 0 0
Gent
Country [13] 0 0
Belgium
State/province [13] 0 0
Roeselare
Country [14] 0 0
Denmark
State/province [14] 0 0
Herlev
Country [15] 0 0
France
State/province [15] 0 0
Angers
Country [16] 0 0
France
State/province [16] 0 0
Brest
Country [17] 0 0
France
State/province [17] 0 0
Caen
Country [18] 0 0
France
State/province [18] 0 0
Dijon
Country [19] 0 0
France
State/province [19] 0 0
Grenoble
Country [20] 0 0
France
State/province [20] 0 0
Lille
Country [21] 0 0
France
State/province [21] 0 0
Lyon
Country [22] 0 0
France
State/province [22] 0 0
Marseille cedex 20
Country [23] 0 0
France
State/province [23] 0 0
Pessac
Country [24] 0 0
France
State/province [24] 0 0
Rennes
Country [25] 0 0
France
State/province [25] 0 0
St Herblain
Country [26] 0 0
France
State/province [26] 0 0
Strasbourg
Country [27] 0 0
France
State/province [27] 0 0
Toulouse
Country [28] 0 0
Germany
State/province [28] 0 0
Berlin
Country [29] 0 0
Germany
State/province [29] 0 0
Düsseldorf
Country [30] 0 0
Germany
State/province [30] 0 0
Großhansdorf
Country [31] 0 0
Germany
State/province [31] 0 0
Hemer
Country [32] 0 0
Germany
State/province [32] 0 0
Koeln
Country [33] 0 0
Germany
State/province [33] 0 0
Rheine
Country [34] 0 0
Italy
State/province [34] 0 0
Emilia-Romagna
Country [35] 0 0
Italy
State/province [35] 0 0
Friuli-Venezia Giulia
Country [36] 0 0
Italy
State/province [36] 0 0
Lazio
Country [37] 0 0
Italy
State/province [37] 0 0
Lombardia
Country [38] 0 0
Italy
State/province [38] 0 0
Toscana
Country [39] 0 0
Italy
State/province [39] 0 0
Umbria
Country [40] 0 0
Korea, Republic of
State/province [40] 0 0
Gyeonggi-do
Country [41] 0 0
Korea, Republic of
State/province [41] 0 0
Seoul
Country [42] 0 0
Luxembourg
State/province [42] 0 0
Luxembourg
Country [43] 0 0
Netherlands
State/province [43] 0 0
Amsterdam
Country [44] 0 0
Netherlands
State/province [44] 0 0
Groningen
Country [45] 0 0
Netherlands
State/province [45] 0 0
Maastricht
Country [46] 0 0
Russian Federation
State/province [46] 0 0
Moskovskaja Oblast
Country [47] 0 0
Singapore
State/province [47] 0 0
Singapore
Country [48] 0 0
Spain
State/province [48] 0 0
Alicante
Country [49] 0 0
Spain
State/province [49] 0 0
Barcelona
Country [50] 0 0
Spain
State/province [50] 0 0
Madrid
Country [51] 0 0
Spain
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Malaga
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Spain
State/province [52] 0 0
Zaragoza
Country [53] 0 0
Sweden
State/province [53] 0 0
Stockholm
Country [54] 0 0
Taiwan
State/province [54] 0 0
Taichung
Country [55] 0 0
Taiwan
State/province [55] 0 0
Tainan
Country [56] 0 0
Taiwan
State/province [56] 0 0
Taipei
Country [57] 0 0
United Kingdom
State/province [57] 0 0
Aberdeen
Country [58] 0 0
United Kingdom
State/province [58] 0 0
London

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Hoffmann-La Roche
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This open-label, non-randomized, multicenter, Phase 1/2 study will evaluate the safety and efficacy of alectinib in participants with non-small cell lung cancer who have ALK mutation and failed crizotinib treatment. In Part 1, cohorts of participants will receive escalating doses of alectinib orally twice daily. In Part 2, participants will receive the recommended phase 2 dose (RP2D) of alectinib 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, participants without epidermal growth factor receptor (EGFR) mutation will be offered continued treatment with alectinib, participants with EGFR mutations will be offered a combination of alectinib and erlotinib.
Trial website
https://clinicaltrials.gov/study/NCT01801111
Trial related presentations / publications
Ou SI, Gadgeel SM, Barlesi F, Yang JC, De Petris L, Kim DW, Govindan R, Dingemans AM, Crino L, Lena H, Popat S, Ahn JS, Dansin E, Mitry E, Muller B, Bordogna W, Balas B, Morcos PN, Shaw AT. Pooled overall survival and safety data from the pivotal phase II studies (NP28673 and NP28761) of alectinib in ALK-positive non-small-cell lung cancer. Lung Cancer. 2020 Jan;139:22-27. doi: 10.1016/j.lungcan.2019.10.015. Epub 2019 Oct 14.
Morcos PN, Nueesch E, Jaminion F, Guerini E, Hsu JC, Bordogna W, Balas B, Mercier F. Exposure-response analysis of alectinib in crizotinib-resistant ALK-positive non-small cell lung cancer. Cancer Chemother Pharmacol. 2018 Jul;82(1):129-138. doi: 10.1007/s00280-018-3597-5. Epub 2018 May 10.
Gadgeel SM, Shaw AT, Govindan R, Gandhi L, Socinski MA, Camidge DR, De Petris L, Kim DW, Chiappori A, Moro-Sibilot DL, Duruisseaux M, Crino L, De Pas T, Dansin E, Tessmer A, Yang JC, Han JY, Bordogna W, Golding S, Zeaiter A, Ou SI. Pooled Analysis of CNS Response to Alectinib in Two Studies of Pretreated Patients With ALK-Positive Non-Small-Cell Lung Cancer. J Clin Oncol. 2016 Dec;34(34):4079-4085. doi: 10.1200/JCO.2016.68.4639. Epub 2016 Oct 31. Erratum In: J Clin Oncol. 2017 May 10;35(14):1631. doi: 10.1200/JCO.2017.73.5142.
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Trials
Address 0 0
Hoffmann-La Roche
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT01801111