A Study of Alectinib (CH5424802/RO5424802) in Participants With Anaplastic Lymphoma Kinase (ALK)-Rearranged Non-Small Cell Lung Cancer (NSCLC)

NCT01871805 | Completed Phase 1 Results

• 1 other identifier: NP28761
• Study Type: interventional
• Target: 134
• Locations: 2 countries
• Sites: 42

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.

Conditions

Non-Small Cell Lung Cancer

Outcome Measures

Primary Outcomes (3)

• Number of Participants With Dose Limiting Toxicities (DLTs): Phase I

  The DLTs were defined as any which included Grade 4 thrombocytopenia or Grade 3 thrombocytopenia with bleeding or Grade 4 neutropenia continuing for greater than equal to (\>=) 7 consecutive days, non-hematological toxicity of Grade 3 or higher (excluding transient electrolyte abnormalities, diarrhea, nausea, and vomiting that recovers to Grade 2 or lower with appropriate treatment and participants having Grade 2 aspartate transaminase (AST) and/or alanine transaminase (ALT) at baseline must have Grade 3 AST/ALT for 7 days or Grade 4 AST/ALT to be considered a DLT), and adverse events (AEs) that required suspension of treatment for a total of \>=7 days which the Investigator could not rule out as been related to alectinib.

  Throughout Cycle 1 of Phase I (21 days)

• Recommended Phase II Dose (RP2D): Phase I

  RP2D was defined as the highest dose with acceptable toxicity as determined from Phase I of the study.

  Throughout Cycle 1 of Phase I (21 days)

• 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

  Percentage of participants with objective response as assessed by IRC was defined as the percentage of responders in the response evaluable population, where responders were defined as participants determined to have a best overall response of complete response (CR) or partial response (PR) based on the RECIST v1.1 criteria. CR: disappearance of all target and non-target lesions (TLs) and normalization of tumor markers. Pathological lymph nodes must have short axis measures less than (\<) 10 millimeter (mm). PR: at least a 30 percent (%) decrease in the sum of measures (longest diameter for tumor lesions and short axis measure for nodes) of TLs, taking as reference the baseline sum of diameters. CR and PR were to be confirmed by repeat assessments \>=4 weeks after initial documentation. Clopper-Pearson method was used to calculate 95% confidence interval (CI).

  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 (25)

• Percentage of Participants With Objective Response According to RECIST v1.1 by Investigator: Phase I

  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)

• Duration of Response (DOR) According to RECIST v1.1 by Investigator: Phase I

  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)

• Percentage of Participants With Objective Response According to RECIST v1.1 by Investigator: Phase II

  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)

• Percentage of Participants With Disease Control According to RECIST v1.1 by Investigator: Phase II

  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)

• Percentage of Participants With Disease Progression According to RECIST v1.1 by IRC or Death : Phase II

  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)

Study Arms (2)

Alectinib: Phase I (Dose Escalation)

EXPERIMENTAL

Participants will receive escalating doses of alectinib capsules orally until disease progression, death or withdrawal for any other reasons.

Drug: Alectinib

Alectinib (Phase II: RP2 dose)

EXPERIMENTAL

Participants will receive recommended Phase II dose as determined from Phase I until disease progression, death or withdrawal for any other reasons.

Drug: Alectinib

Interventions

Alectinib DRUG

Participants will receive alectinib as described in the arm descriptions.

Also known as: CH5424802, RO5424802

Alectinib (Phase II: RP2 dose); Alectinib: Phase I (Dose Escalation)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (42)

University of Alabama at Birmingham

Birmingham, Alabama, 35233, United States

Location

University of California Irvine

Irvine, California, 92697, United States

Location

UCSD Moores Cancer Center

La Jolla, California, 92093, United States

Location

Loma Linda Cancer Center

Loma Linda, California, 92354, United States

Location

UCLA

Los Angeles, California, 90095, United States

Location

Univ of Colorado Canc Ctr

Aurora, Colorado, 80045, United States

Location

National Jewish Health

Denver, Colorado, 80206, United States

Location

Lynn Regional Cancer Center West

Boca Raton, Florida, 33486, United States

Location

Florida Hospital Cancer Inst

Orlando, Florida, 32804, United States

Location

UF Health Orlando

Orlando, Florida, 32806, United States

Location

H. Lee Moffitt Cancer Center and Research Inst.

Tampa, Florida, 33612, United States

Location

University of Illinois Cancer Center

Chicago, Illinois, 60612, United States

Location

Monroe Medical Associates; Ingalls Memorial Hosp

Harvey, Illinois, 60426, United States

Location

Massachussets General Hospital

Boston, Massachusetts, 02114, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Dana Farber Can Ins

Boston, Massachusetts, 02215, United States

Location

Newton-Wellesley Hospital

Newton, Massachusetts, 02462, United States

Location

St. Joseph Mercy Hospital; Cancer Care Center.

Ann Arbor, Michigan, 48106, United States

Location

Wayne State Uni ; Karmanos Cancer Center

Detroit, Michigan, 48201, United States

Location

Hackensack Univ Med Ctr

Hackensack, New Jersey, 07601, United States

Location

Roswell Park Cancer Inst.

Buffalo, New York, 14263, United States

Location

Memorial Sloan-Kettering Cancer Center

Commack, New York, 11725, United States

Location

Richmond University Medical Center; Pharmacy Department

Staten Island, New York, 10310, United States

Location

Wake Forest University Health Sciences

Winston-Salem, North Carolina, 27157, United States

Location

Gabrail Cancer Center

Canton, Ohio, 44718, United States

Location

The Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

Providence Portland Med Ctr

Portland, Oregon, 97213, United States

Location

Oregon Health & Science Uni

Portland, Oregon, 97239, United States

Location

St. Luke's Hospital; Pharmacy Department

Bethlehem, Pennsylvania, 18015, United States

Location

Penn State Hershey Cancer Institute

Hershey, Pennsylvania, 17033, United States

Location

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, United States

Location

University of Pittsburgh Cancer Pavillion

Pittsburgh, Pennsylvania, 15232, United States

Location

MUSC Hollings Cancer Center

Charleston, South Carolina, 29425, United States

Location

Center for Biomedical Research LLC

Knoxville, Tennessee, 37909, United States

Location

Texas Oncology-Baylor Sammons Cancer Center

Dallas, Texas, 75246, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Virginia Cancer Specialists, PC

Fairfax, Virginia, 22031, United States

Location

Swedish Cancer Inst.

Seattle, Washington, 98104, United States

Location

University of Wisconsin

Madison, Wisconsin, 53792, United States

Location

Cross Cancer Institute

Edmonton, Alberta, T6G 1Z2, Canada

Location

Lakeridge Health Oshawa; Oncology

Oshawa, Ontario, L1G 2B9, Canada

Location

McGill University; Sir Mortimer B Davis Jewish General Hospital; Oncology

Montreal, Quebec, H3T 1E2, Canada

Location

Related Publications (7)

• 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.

  PMID: 32009824 DERIVED

• 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.

  PMID: 31706099 DERIVED

• 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.

  PMID: 29748847 DERIVED

• 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.

  PMID: 27863201 DERIVED

• 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.

  PMID: 27130468 DERIVED

• 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. Erratum In: Lancet Oncol. 2017 Mar;18(3):e134. doi: 10.1016/S1470-2045(17)30077-3.

  PMID: 26708155 DERIVED

• 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.

  PMID: 25153538 DERIVED

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

alectinib

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffmann-LaRoche

genentech@druginfo.com

800-821-8590

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 28, 2013
• First Posted: June 7, 2013
• Study Start: September 30, 2013
• Primary Completion: October 24, 2014
• Study Completion: August 31, 2017
• Last Updated: August 21, 2018
• Results First Posted: February 12, 2016

Record last verified: 2018-07

Locations

CA (3); US (39)