Clinical trial NCT01871805: A Study of Alectinib (CH5424802/RO5424802) in Participants With Anaplastic Lymphoma Kinase (ALK)-Rearranged Non-Small Cell Lung Cancer (NSCLC)
Official title: A Phase I/II Study of the ALK Inhibitor CH5424802/ RO5424802 in Patients With ALK-Rearranged Non-Small Cell Lung Cancer Previously Treated With Crizotinib
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Non-Small Cell Lung Cancer
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2013-06-07
Enrollment: 134
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This non-randomized, open-label, multicenter study will evaluate the safety and efficacy of alectinib in participants with ALK-rearranged non-small cell lung cancer who failed crizotinib treatment. In Phase I, cohorts of participants will receive escalating doses of alectinib orally twice daily. In Phase II, patients who failed crizotinib treatment will receive the recommended phase II dose.


Eligibility criteria: Inclusion Criteria:

* Histologically confirmed, locally advanced, not amenable to curative therapy, or metastatic NSCLC
* ALK-rearrangement confirmed by the Food and Drug Administration (FDA) approved test
* NSCLC that has failed crizotinib treatment
* Measurable disease as defined by RECIST v1.1
* Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to (\<=) 2
* Adequate hematologic, hepatic and renal function

Exclusion Criteria:

* Prior therapy with ALK inhibitor other than crizotinib
* Brain or leptomeningeal metastases that are symptomatic and/or requiring treatment
* History of serious cardiac dysfunction
* History of or current active infection with hepatitis B, hepatitis C or human immunodeficiency virus (HIV)
* Clinically significant gastrointestinal abnormality that would affect absorption of the drug
* Pregnant or lactating women

Primary outcomes:
measure: Number of Participants With Dose Limiting Toxicities (DLTs): Phase I
timeFrame: Throughout Cycle 1 of Phase I (21 days)
measure: Recommended Phase II Dose (RP2D): Phase I
timeFrame: Throughout Cycle 1 of Phase I (21 days)
measure: Percentage of Participants With Objective Response According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) by Independent Review Committee (IRC): Phase II
timeFrame: Cycle 1 Day 1 up to 194 weeks (assessed at every 6 weeks from Cycle 1 Day 1, at Cycles 2, 4, and 6 between Days 14-21, and every 3 cycles thereafter) (1 cycle = 21 days)
Secondary outcomes:
measure: Percentage of Participants With Objective Response According to RECIST v1.1 by Investigator: Phase I
timeFrame: Every 6 weeks from Cycle 1 Day 1, at Cycles 2, 4, and 6 between Days 14-21, and every 3 cycles thereafter (assessed up to 194 weeks) (1 cycle = 21 days)
measure: Duration of Response (DOR) According to RECIST v1.1 by Investigator: Phase I
timeFrame: Every 6 weeks from Cycle 1 Day 1, at Cycles 2, 4, and 6 between Days 14-21, and every 3 cycles thereafter (assessed up to 194 weeks) (1 cycle = 21 days)
measure: Percentage of Participants With Objective Response According to RECIST v1.1 by Investigator: Phase II
timeFrame: Every 6 weeks from Cycle 1 Day 1, at Cycles 2, 4, and 6 between Days 14-21, and every 3 cycles thereafter (assessed up to 194 weeks) (1 cycle = 21 days)
measure: Percentage of Participants With Disease Control According to RECIST v1.1 by Investigator: Phase II
timeFrame: Every 6 weeks from Cycle 1 Day 1, at Cycles 2, 4, and 6 between Days 14-21, and every 3 cycles thereafter (assessed up to 194 weeks) (1 cycle = 21 days)
measure: Percentage of Participants With Disease Progression According to RECIST v1.1 by IRC or Death : Phase II
timeFrame: Every 6 weeks from Cycle 1 Day 1, at Cycles 2, 4, and 6 between Days 14-21, and every 3 cycles thereafter (assessed up to 194 weeks) (1 cycle = 21 days)
measure: Progression-Free Survival (PFS) According to RECIST v1.1 by IRC: Phase II
timeFrame: Every 6 weeks from Cycle 1 Day 1, at Cycles 2, 4, and 6 between Days 14-21, and every 3 cycles thereafter (assessed up to 194 weeks) (1 cycle = 21 days)
measure: Percentage of Participants With Disease Progression According to RECIST v1.1 by Investigator or Death : Phase II
timeFrame: Every 6 weeks from Cycle 1 Day 1, at Cycles 2, 4, and 6 between Days 14-21, and every 3 cycles thereafter (assessed up to 194 weeks) (1 cycle = 21 days)
measure: PFS According to RECIST v1.1 by Investigator: Phase II
timeFrame: Every 6 weeks from Cycle 1 Day 1, at Cycles 2, 4, and 6 between Days 14-21, and every 3 cycles thereafter (assessed up to 194 weeks) (1 cycle = 21 days)
measure: Percentage of Participants Who Died Due to Any Cause: Phase II
timeFrame: Baseline up to death (any cause) (maximum follow up 284 weeks)
measure: Overall Survival (OS) Time: Phase II
timeFrame: Baseline up to death (any cause) (maximum follow up 284 weeks)
measure: DOR According to RECIST v1.1 by IRC: Phase II
timeFrame: Every 6 weeks from Cycle 1 Day 1, at Cycles 2, 4, and 6 between Days 14-21, and every 3 cycles thereafter (assessed up to 194 weeks) (1 cycle = 21 days)
measure: DOR According to RECIST v1.1 by Investigator: Phase II
timeFrame: Every 6 weeks from Cycle 1 Day 1, at Cycles 2, 4, and 6 between Days 14-21, and every 3 cycles thereafter (assessed up to 194 weeks) (1 cycle = 21 days)
measure: Percentage of Participants With Central Nervous System Objective Response (COR) According to RECIST v1.1 by IRC: Phase II
timeFrame: Every 6 weeks from Cycle 1 Day 1, at Cycles 2, 4, and 6 between Days 14-21, and every 3 cycles thereafter (assessed up to 194 weeks) (1 cycle = 21 days)
measure: Percentage of Participants With COR According to Response Assessment in Neuro-Oncology (RANO) Criteria by IRC: Phase II
timeFrame: Every 6 weeks from Cycle 1 Day 1, at Cycles 2, 4, and 6 between Days 14-21, and every 3 cycles thereafter (assessed up to 194 weeks) (1 cycle = 21 days)
measure: CNS Duration of Response (CDOR) According to RECIST v1.1 by IRC: Phase II
timeFrame: Every 6 weeks from Cycle 1 Day 1, at Cycles 2, 4, and 6 between Days 14-21, and every 3 cycles thereafter (assessed up to 194 weeks) (1 cycle = 21 days)
measure: CDOR According to RANO Criteria by IRC: Phase II
timeFrame: Every 6 weeks from Cycle 1 Day 1, at Cycles 2, 4, and 6 between Days 14-21, and every 3 cycles thereafter (assessed up to 194 weeks) (1 cycle = 21 days)
measure: Percentage of Participants With CNS Progression According to RECIST v1.1 by IRC: Phase II
timeFrame: Every 6 weeks from Cycle 1 Day 1, at Cycles 2, 4, and 6 between Days 14-21, and every 3 cycles thereafter (assessed up to 194 weeks) (1 cycle = 21 days)
measure: Percentage of Participants With CNS Progression According to RANO Criteria by IRC: Phase II
timeFrame: Every 6 weeks from Cycle 1 Day 1, at Cycles 2, 4, and 6 between Days 14-21, and every 3 cycles thereafter (assessed up to 194 weeks) (1 cycle = 21 days)
measure: Maximum Observed Plasma Concentration (Cmax) After Single Dose of Alectinib: Phase I
timeFrame: Pre-dose (0 hour), 0.5, 1, 2, 4, 6, 8, 10, 24, 32 and 48 hours post-dose on Cycle 1 Day -3 (1 cycle = 21 days)
measure: Cmax After Multiple Dose of Alectinib: Phase I
timeFrame: Pre-dose (0 hour), 0.5, 1, 2, 4, 6, 8 and 10 hours post-dose on Cycle 2 Day 1 (1 cycle = 21 days)
measure: Area Under the Plasma Concentration (AUC) Versus Time Curve Extrapolated to Infinity (AUCinf) After Single Dose of Alectinib: Phase I
timeFrame: Pre-dose (0 hour), 0.5, 1, 2, 4, 6, 8, 10, 24, 32 and 48 hours post-dose on Cycle 1 Day -3 (1 cycle = 21 days)
measure: AUC From Time Zero to Last Measurable Concentration (AUClast) After Multiple Dose of Alectinib: Phase I
timeFrame: Pre-dose (0 hour), 0.5, 1, 2, 4, 6, 8 and 10 hours post-dose on Cycle 2 Day 1 (1 cycle = 21 days)
measure: Ctrough After Multiple Dose of Alectinib: Phase II
timeFrame: Pre-dose (0 hour) on Day 1 of Cycles 2, Cycle 3, Cycle 4, Cycle 5 (1 cycle = 21 days)
measure: Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30): Phase II
timeFrame: Baseline, Weeks 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48, 51, 54, 57, 60, 63, 66, 69, 72, 75, 78, 81, 84, 87, 90, 93, 96, 99, 105, 111, 117, last visit (up to 194 weeks)
measure: Change From Baseline in EORTC Quality of Life Questionnaire Lung Cancer 13 (EORTC QLQ-LC13): Phase II
timeFrame: Baseline, Weeks 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48, 51, 54, 57, 60, 63, 66, 69, 72, 75, 78, 81, 84, 87, 90, 93, 96, 99, 105, 111, 117, last visit (up to 194 weeks)
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Irvine
country: United States
facility: University of California Irvine
state: California
city: La Jolla
country: United States
facility: UCSD Moores Cancer Center
state: California
city: Loma Linda
country: United States
facility: Loma Linda Cancer Center
state: California
city: Los Angeles
country: United States
facility: UCLA
state: California
city: Aurora
country: United States
facility: Univ of Colorado Canc Ctr
state: Colorado
city: Denver
country: United States
facility: National Jewish Health
state: Colorado
city: Boca Raton
country: United States
facility: Lynn Regional Cancer Center West
state: Florida
city: Orlando
country: United States
facility: Florida Hospital Cancer Inst
state: Florida
city: Orlando
country: United States
facility: UF Health Orlando
state: Florida
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center and Research Inst.
state: Florida
city: Chicago
country: United States
facility: University of Illinois Cancer Center
state: Illinois
city: Harvey
country: United States
facility: Monroe Medical Associates; Ingalls Memorial Hosp
state: Illinois
city: Boston
country: United States
facility: Massachussets General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Dana Farber Can Ins
state: Massachusetts
city: Newton
country: United States
facility: Newton-Wellesley Hospital
state: Massachusetts
city: Ann Arbor
country: United States
facility: St. Joseph Mercy Hospital; Cancer Care Center.
state: Michigan
city: Detroit
country: United States
facility: Wayne State Uni ; Karmanos Cancer Center
state: Michigan
city: Hackensack
country: United States
facility: Hackensack Univ Med Ctr
state: New Jersey
city: Buffalo
country: United States
facility: Roswell Park Cancer Inst.
state: New York
city: Commack
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
city: Staten Island
country: United States
facility: Richmond University Medical Center; Pharmacy Department
state: New York
city: Winston-Salem
country: United States
facility: Wake Forest University Health Sciences
state: North Carolina
city: Canton
country: United States
facility: Gabrail Cancer Center
state: Ohio
city: Columbus
country: United States
facility: The Ohio State University Comprehensive Cancer Center
state: Ohio
city: Portland
country: United States
facility: Providence Portland Med Ctr
state: Oregon
city: Portland
country: United States
facility: Oregon Health & Science Uni
state: Oregon
city: Bethlehem
country: United States
facility: St. Luke's Hospital; Pharmacy Department
state: Pennsylvania
city: Hershey
country: United States
facility: Penn State Hershey Cancer Institute
state: Pennsylvania
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Cancer Pavillion
state: Pennsylvania
city: Charleston
country: United States
facility: MUSC Hollings Cancer Center
state: South Carolina
city: Knoxville
country: United States
facility: Center for Biomedical Research LLC
state: Tennessee
city: Dallas
country: United States
facility: Texas Oncology-Baylor Sammons Cancer Center
state: Texas
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Fairfax
country: United States
facility: Virginia Cancer Specialists, PC
state: Virginia
city: Seattle
country: United States
facility: Swedish Cancer Inst.
state: Washington
city: Madison
country: United States
facility: University of Wisconsin
state: Wisconsin
city: Edmonton
country: Canada
facility: Cross Cancer Institute
state: Alberta
city: Oshawa
country: Canada
facility: Lakeridge Health Oshawa; Oncology
state: Ontario
city: Montreal
country: Canada
facility: McGill University; Sir Mortimer B Davis Jewish General Hospital; Oncology
state: Quebec
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Gadgeel S, Shaw AT, Barlesi F, Crino L, Yang JC, Dingemans AM, Kim DW, de Marinis F, Schulz M, Liu S, Gupta R, Smoljanovic V, Ou SI. Time To Response In Patients With Advanced Anaplastic Lymphoma Kinase (ALK)-Positive Non-Small-Cell Lung Cancer (NSCLC) Receiving Alectinib In The Phase II NP28673 And NP28761 Studies. Lung Cancer (Auckl). 2019 Nov 13;10:125-130. doi: 10.2147/LCTT.S209231. eCollection 2019.
citation: 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.
citation: 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.
citation: 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.
citation: Lin YT, Yu CJ, Yang JC, Shih JY. Anaplastic Lymphoma Kinase (ALK) Kinase Domain Mutation Following ALK Inhibitor(s) Failure in Advanced ALK Positive Non-Small-Cell Lung Cancer: Analysis and Literature Review. Clin Lung Cancer. 2016 Sep;17(5):e77-e94. doi: 10.1016/j.cllc.2016.03.005. Epub 2016 Mar 30.
citation: Shaw AT, Gandhi L, Gadgeel S, Riely GJ, Cetnar J, West H, Camidge DR, Socinski MA, Chiappori A, Mekhail T, Chao BH, Borghaei H, Gold KA, Zeaiter A, Bordogna W, Balas B, Puig O, Henschel V, Ou SI; study investigators. Alectinib in ALK-positive, crizotinib-resistant, non-small-cell lung cancer: a single-group, multicentre, phase 2 trial. Lancet Oncol. 2016 Feb;17(2):234-242. doi: 10.1016/S1470-2045(15)00488-X. Epub 2015 Dec 19.
citation: Gadgeel SM, Gandhi L, Riely GJ, Chiappori AA, West HL, Azada MC, Morcos PN, Lee RM, Garcia L, Yu L, Boisserie F, Di Laurenzio L, Golding S, Sato J, Yokoyama S, Tanaka T, Ou SH. Safety and activity of alectinib against systemic disease and brain metastases in patients with crizotinib-resistant ALK-rearranged non-small-cell lung cancer (AF-002JG): results from the dose-finding portion of a phase 1/2 study. Lancet Oncol. 2014 Sep;15(10):1119-28. doi: 10.1016/S1470-2045(14)70362-6. Epub 2014 Aug 18.