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Trial of Brigatinib After Treatment With Second-Generation ALK Inhibitors

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ClinicalTrials.gov Identifier: NCT02706626
Recruitment Status : Recruiting
First Posted : March 11, 2016
Last Update Posted : October 18, 2017
University of Colorado, Denver
Duke University
Ariad Pharmaceuticals
Information provided by (Responsible Party):
Criterium, Inc.

Brief Summary:
The purpose of this study is to evaluate the safety and effectiveness of this investigational drug, brigatinib (AP261136) in patients with advanced non-small cell lung cancer Non-small cell lung cancer (NSCLC) who have had first-line treatment for their cancer and it still got worse, even after, or while taking drugs called ALK inhibitors, or anti-cancer drugs that act on tumors. Some examples of these anti-cancer drugs are: KEYTRUDA® or ALECENSA®).

Condition or disease Intervention/treatment Phase
Non-Small Cell Lung Cancer Drug: brigatinib Phase 2

Detailed Description:

A significant population of Anaplastic Lymphoma Kinase (ALK) plus Non-small cell lung cancer patients exist that have progressed on or who were intolerant of second generation anaplastic lymphoma kinase inhibitor (e.g. ceritinib or alectinib). Brigatinib has demonstrated activity in patients who have progressed on crizotinib, but the activity of brigatinib in patients who have progressed on ceritinib, alectinib, or other second generation anaplastic lymphoma kinase inhibitors is unknown. Based on the preclinical data. 3, brigatinib is the only known anaplastic lymphoma kinase inhibitor with potent activity against known secondary anaplastic lymphoma kinase mutations suggesting it may retain activity as third-line treatment of anaplastic lymphoma kinase plus disease.

Patients enrolled in ARI-AT-002 must have previously received a second generation Anaplastic lymphoma kinase inhibitor other than brigatinib. Given that third-line treatment of anaplastic lymphoma kinase plus disease is analogous to a phase I population, we have chosen 20% as a clinically meaningful response rate that would justify further study of brigatinib in previously treated anaplastic lymphoma kinase plus disease.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase 2 Trial of Brigatinib After Treatment With Second-Generation ALK Inhibitors in Refractory ALK Rearranged Non-Small Cell Lung Cancer (NSCLC)
Actual Study Start Date : March 9, 2017
Estimated Primary Completion Date : June 2018
Estimated Study Completion Date : June 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lung Cancer
Drug Information available for: Brigatinib
U.S. FDA Resources

Arm Intervention/treatment
Experimental: Brigatinib
Experimental: Brigatinib until progressive disease, unacceptable toxicity, withdrawal of consent
Drug: brigatinib
Single arm phase 2 trial to investigate the clinical activity in patients with advanced non-small cell lung cancer
Other Name: AP26113

Primary Outcome Measures :
  1. Overall response rate (complete response plus partial response) [ Time Frame: 24-48 months ]
    Estimate overall response rate (rate of complete response plus partial response of brigatinib in patients with Anaplastic lymphoma kinase plus non small cell lung cancer who have progressed on second generation ALK inhibitors (e.g., alectinib or ceritinib)

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Locally advanced or metastatic non small cell lung cancer that has been cytologically or histologically confirmed
  • Anaplastic lymphoma kinase rearrangement based on FDA approved test (e.g., Vysius break apart fluorescence in situ hybridization (FISH) or Immunohistochemistry (IHC) using Ventana)
  • Eastern Cooperative Oncology Group (ECOG) performance status greater than or equal to 2
  • Age 18 years or older
  • Previous treatment with one second generation ALK inhibitor (e.g., ceritinib or alectinib) other than brigatinib
  • Brain lesions may be used as target lesions if progressing, are greater than or equal to 10mm in longest diameter and if they were not previously treated with any of the following: whole brain radiation therapy within 3 months; Stereotactic radiosurgery; surgical resection
  • Availability of core biopsy of progressive lesion taken within 60 days prior to D1 of treatment under study therapy or willing to undergo tumor biopsy: NOTE:. All subjects must consent to provide tumor blocks or slides. If archival tissue is not available and biopsies to obtain fresh tumor tissue cannot be performed with minimal risk to the subject, subjects may be permitted to enroll on the study with prior approval of the Study PI.
  • Recovered from toxicities related to prior anticancer treatment to greater than or equal to grade 2 or baseline with the exception of alopecia
  • Have normal QT interval on ECG evaluation QT corrected Fridericia (QTcF) of ≤ 450 ms in males or ≤ 470 ms in females
  • Adequate organ function
  • At least 1 measurable lesion per RECIST version 1.1
  • Negative serum pregnancy test within 7 days of day 1 of treatment in women of childbearing potential
  • If fertile, willing to use highly effective form of contraception during the dosing period and for at least 4 months after the dosing period
  • Ability to provide signed informed consent and willing and able to comply with all study requirements

Exclusion Criteria:

  • History or the presence of pulmonary interstitial disease, drug-related pneumonitis, or radiation pneumonitis
  • Prior treatment with brigatinib
  • History of or active significant gastrointestinal bleeding within 3 months
  • Malabsorption syndrome or other gastrointestinal illness that could affect oral absorption of the study drug
  • Received cytotoxic chemotherapy, investigational agents or radiation within 7 days prior to day 1 of study treatment
  • Received prior ALK TKI therapy within 7 days prior to day 1 of treatment under study drug. 7 day wash out period is required after prior ALK inhibitor treatment
  • Have significant, uncontrolled, or active cardiovascular disease
  • Have been diagnosed with another primary malignancy within the past 3 years (except for adequately treated non-melanoma skin cancer, cervical cancer in situ, or prostate cancer, which are allowed within 3 years)
  • Have symptomatic central nervous system (CNS) metastases that are neurologically unstable or require an increasing dose of corticosteroids
  • Have active infection requiring intravenous antibiotics
  • Pregnant or breastfeeding
  • Have any condition or illness that, in the opinion of the investigator would compromise patient safety or interfere with evaluation of the study drug

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02706626

Contact: Thomas Stinchcombe, MD 919-668-6509 thomas.stinchcombe@duke.edu

United States, Colorado
University Of Colorado Recruiting
Denver, Colorado, United States, 80045
Contact: Anna Wynfield    720-848-5278    anna.wynfield@ucdenver.edu   
Contact: Paula Fisk    720-848-0676    Paula.Fisk@ucdenver.edu   
Principal Investigator: David R Camidge, MD         
United States, North Carolina
Duke University Recruiting
Durham, North Carolina, United States, 27710
Contact: Debra Shoemaker, RN    919-681-4768    Debra.shoemaker@duke.edu   
Principal Investigator: Thomas E Stinchcombe, MD         
United States, Tennessee
Vanderbilt Unversity Medical Center Not yet recruiting
Nashville, Tennessee, United States, 37203
Principal Investigator: Leora Horn, MD         
United States, Texas
University of Texas, Southwestern Recruiting
Dallas, Texas, United States, 75390
Contact: Sarah Burris    214-648-4034    sarah.burris@utsouthwestern.edu   
Principal Investigator: David Gerber, MD         
Sponsors and Collaborators
Criterium, Inc.
University of Colorado, Denver
Duke University
Ariad Pharmaceuticals
Principal Investigator: Thomas Stinchcombe, MD Duke University

Responsible Party: Criterium, Inc.
ClinicalTrials.gov Identifier: NCT02706626     History of Changes
Other Study ID Numbers: ARI-AT-002
First Posted: March 11, 2016    Key Record Dates
Last Update Posted: October 18, 2017
Last Verified: October 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms