Trial of Brigatinib After Treatment With Next-Generation ALK Inhibitors

NCT02706626 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: ARI-AT-002
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 4

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®).

Conditions

Non-Small Cell Lung Cancer

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate

  An assessment of the response using RECIST 1.1 per investigator. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.". The enrollment in the clinical trial did not reach the target number of subjects needed to achieve target power and was insufficient to produce statistically reliable results

  Through study completion (average 42 months)

Study Arms (3)

Cohort A: Disease progression after next generation ALK TKI

EXPERIMENTAL

Brigatinib until progressive disease, unacceptable toxicity, withdrawal of consent. Patients enrolled regardless the number of lines of therapy

Drug: brigatinib

Cohort B: Disease progression after alectinib as first-line therapy

EXPERIMENTAL

Brigatinib until progressive disease, unacceptable toxicity, withdrawal of consent. Patients enrolled after first-line alectinib

Drug: brigatinib

Cohort C: Disease progression after brigatinib

EXPERIMENTAL

Brigatinib at 240 mg daily until progressive disease, unacceptable toxicity, withdrawal of consent. Patients enrolled after treatment on brigatinib at the standard dose brigatinib

Drug: brigatinib

Interventions

brigatinib DRUG

Single arm phase 2 trial to investigate the clinical activity in patients with advanced non-small cell lung cancer

Also known as: AP26113

Cohort A: Disease progression after next generation ALK TKI; Cohort B: Disease progression after alectinib as first-line therapy; Cohort C: Disease progression after brigatinib

Eligibility Criteria

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

You may qualify if:

• Locally advanced or metastatic NSCLC that has been cytologically or histologically confirmed
• ALK rearrangement based on FDA approved test (e.g. Vysis breakapart FISH or IHC using Ventana)
• ECOG PS ≤2
• Age of ≥ 18 years
• Brain lesions may be used as target lesions if progressing, ≥10mm in longest diameter and if they were not previously treated with any of the following:
• Whole brain radiation therapy (WBRT) within 3 months
• Stereotactic radiosurgery (SRS)
• 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.
• In the situation the patient undergoes biopsy within 60 days prior to D1. and there is insufficient tumor tissue subjects for the correlative science part of the protocol patient will be permitted to enroll on the study with prior approval of the study PI
• In the situation the patient undergoes molecular testing or next-generation sequencing as part of standard care there must be sufficient tumor sample available for participation in the study (i.e. a next generation sequencing report is not sufficient for enrollment)
• Recovered from toxicities related to prior anticancer treatment 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 defined as:
• Absolute neutrophil count (ANC) ≥1500/µL Platelets ≥75,000/µL Hemoglobin≥ 10g/dL AST /ALT ≤ 2.5 x upper limit of normal (ULN); ≤ 5 x ULN if liver metastasis Total serum bilirubin ≤ 1.5 x ULN Serum creatinine ≤ 1.5 x UNL Serum amylase ≤ 1.5 x UNL

You may not qualify if:

• History or the presence of pulmonary interstitial disease, drug-related or immune-related pneumonitis, or radiation pneumonitis requiring medical management within 6 months of trial enrollment
• Prior treatment with brigatinib for cohorts A and B
• History of or active significant gastrointestinal (GI) bleeding within 3 months
• Malabsorption syndrome or other GI illness that could affect oral absorption of the study drug
• Received cytotoxic chemotherapy, investigational agents or radiation within 7 days prior to D1 of study treatment
• Received prior ALK TKI therapy within 7 days prior to D1 of treatment under study drug. 7 day wash out period is required after prior ALK inhibitor treatment.
• Have significant, uncontrolled, or active cardiovascular disease, specifically including, but not restricted to:
• Myocardial infarction (MI) within 6 months of trial enrollment
• Unstable angina within 6 months of trial enrollment
• Congestive heart failure (CHF) with 6 months prior to trial enrollment
• Any history of ventricular arrhythmia
• Cerebrovascular accident or transient ischemic attack within 6 months of D1 of study treatment
• Clinically significant atrial arrhythmia or severe baseline bradycardia defined as resting heart rate \< 60 beat per minute
• Uncontrolled hypertension defined as baseline SBP\> 160 and DBP \> 100 on 3 separate clinic visits or past history of hypertensive urgency, emergency or encephalopathy
• 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)

Sponsors & Collaborators

• Criterium, Inc.: lead
• University of Colorado, Denver: collaborator
• Duke University: collaborator
• Takeda: collaborator
• Vanderbilt University: collaborator
• University of Texas Southwestern Medical Center: collaborator
• University of Pittsburgh: collaborator
• Ohio State University: collaborator
• Georgetown University: collaborator
• Academic Thoracic Oncology Medical Investigators Consortium: collaborator

Study Sites (4)

University Of Colorado

Denver, Colorado, 80045, United States

Location

Duke University

Durham, North Carolina, 27710, United States

Location

Vanderbilt Unversity Medical Center

Nashville, Tennessee, 37203, United States

Location

University of Texas, Southwestern

Dallas, Texas, 75390, United States

Location

Related Publications (1)

• Stinchcombe TE, Doebele RC, Wang X, Gerber DE, Horn L, Camidge DR. Preliminary Clinical and Molecular Analysis Results From a Single-Arm Phase 2 Trial of Brigatinib in Patients With Disease Progression After Next-Generation ALK Tyrosine Kinase Inhibitors in Advanced ALK+ NSCLC. J Thorac Oncol. 2021 Jan;16(1):156-161. doi: 10.1016/j.jtho.2020.09.018. Epub 2020 Oct 8.

  PMID: 33039599 DERIVED

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

brigatinib

Condition Hierarchy (Ancestors)

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

Limitations and Caveats

The study was terminated for slow accrual. The enrollment in the clinical trial did not reach the target number of subjects needed to achieve target power and was insufficient to produce statistically reliable results

Results Point of Contact

• Title: Tom Stinchcombe
• Organization: Criterium, Inc.

Thomas.stinchcombe@duke.edu

9196819509

Study Officials

• Thomas Stinchcombe, MD

  Duke University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 8, 2016
• First Posted: March 11, 2016
• Study Start: March 9, 2017
• Primary Completion: October 8, 2020
• Study Completion: April 1, 2021
• Last Updated: January 26, 2023
• Results First Posted: January 26, 2023

Record last verified: 2023-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)