Clinical Utility of Liquid Biopsy in Brigatinib ALK+ Patients

NCT04223596 | Active Not Recruiting Phase 2

• 2 other identifiers: GECP 19/01_CUBIK2019-002369-36
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 15

Brief Summary

This is an open-label, non-randomised, phase II, exploratory, multi-country and multi-centre clinical trial. Chemotherapy-naïve patients with EML4-ALK rearrangement and with locally advanced or metastatic non-small cell lung cancer patients will be selected. Patients enrolled in the study will receive brigatinib 90mg for the first 7 days (D 1-7 at cycle 1) and then 180mg daily thereafter for QW4 cycles of duration (28 days ±3days). Brigatinib will be administered until progression disease, unacceptable toxicity, patient or physician decision to discontinue or death. Brigatinib may continue beyond disease progression per RECIST v1.1 until loss of clinical benefit, unacceptable toxicity, patient or physician decision to discontinue, or death as per SmPC recommendations. Patient accrual is expected to be completed within 1.5 years excluding a run-in-period of 4-6 months. Treatment and follow-up are expected to extend the study duration to a total of 5 years. Patients will be followed for 1 year after the end of treatment independently of the cause of end of treatment. The study will end once survival follow-up has concluded. The trial will end with the preparation of the final report, scheduled for 5.5 years after the inclusion of the first patient approximately.

Conditions

Lung Cancer; NSCLC; NSCLC Stage IIIB; NSCLC Stage IV

Keywords

Lung cancer; ALK +; locally advanced; metastasic SCLC; brigatinib; non small cell lung cancer

Outcome Measures

Primary Outcomes (1)

• Overall response rate (ORR)

  To evaluate the Overall response rate of brigatinib as measured by investigator. It will be assessed per RECIST v1.1 criteria. ORR is defined as the proportion of patients who have a partial or complete response to therapy; it does not include stable disease and is a direct measure of drug tumoricidal activity.

  From date of randomization until the date of first documented progression or date of death, whichever came first, assessed up to 60 months

Secondary Outcomes (6)

• Duration of response (DOR)

  From date of documentation of tumor response until date of first documented progression, assessed up to 60 months.

• Intracranial overall response rate (ORR)

  From date of documentation of tumor response until date of first documented progression, assessed up to 60 months.

• Progression free survival (PFS) rate

  1 year and 2 years of treatment with Brigatinib

• Overall Survival (OS) rate

  1 year and 2 years of treatment with Brigatinib

• Safety and tolerability: NCI CTCAE v4.0 criteria

  From the subject's written consent to participate in the study through 30 days after the final administration of the drug.

Study Arms (1)

Experimental: Brigatinib Arm

EXPERIMENTAL

Brigatinib 90 mg for the first 7 days and then 180 mg daily thereafter for QW4 cycles of duration (28 days +- 3 days)

Drug: Brigatinib

Interventions

Brigatinib DRUG

Brigatinib 90 mg for the first 7 days (D1-7 at cycle 1) and then 180 mg daily thereafter for QW4 cycles of duration (28 days+-3 days)

Also known as: AP26113

Experimental: Brigatinib Arm

Eligibility Criteria

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

You may qualify if:

• Male or female, aged ≥ 18 years old
• ECOG performance status of 0-2
• Histologically or cytologically confirmed, Stage IIIB or IV NSCLC according to 8th version of the International Association for the Study of Lung Cancer Staging Manual in Thoracic Oncology, that is ALK+
• Patients who have documented locally ALK rearrangement by one of the following methods:
• a positive result from the Vysis® ALK Break-Apart fluorescence in situ hybridization (FISH) Probe Kit; or
• IHC with VENTANA ALK (D5F3) CDx assay
• No prior treatment for Stage IIIB or IV non-squamous NSCLC.
• Having a life expectancy ≥ 3 months
• Patients who have received prior neo-adjuvant, adjuvant chemotherapy, radiotherapy, or chemo-radiotherapy with curative intent for non-metastatic disease must have experienced a treatment-free interval of at least 6 months from enrollment since the last chemotherapy, radiotherapy, or chemo-radiotherapy.
• Untreated or treated CNS metastases allowed, as long as asymptomatic and neurologically stable
• Patients with at least 1 measurable lesion, as defined by RECIST v1.1. Previously irradiated lesions can only be considered as measurable if disease progression has been unequivocally documented at that site since radiation and the previously irradiated lesion is not the only site of disease.
• Normal QT interval (QT) on screening ECG evaluation, defined as QT interval corrected (Fridericia) (QTcF) of ≤ 450 milliseconds (msec) in males of ≤ 470 msec in females
• Adequate hematologic and organ function defined by the following laboratory results obtained within 14 days prior to enrollment:
• (ANC) Neutrophils ≥ 1500 cells/μL without granulocyte colony-stimulating factor support.
• Lymphocyte count ≥ 500/μL.

You may not qualify if:

• Patients with a known sensitizing mutation in the epidermal growth factor receptor (EGFR) gene.
• Patients with a known STK-1 Ligand alteration.
• Patients with a known MDM2 amplification.
• Patients with a known ROS1 translocations.
• Patients that received any prior TKI, including ALK-targeted TKIs or any systemic anticancer therapy for locally advanced or metastasic disease
• Patients that have received chemotherapy or radiation within 14 days of first dose of study drug, except stereotactic radiosurgery (SRS) or stereotactic body radiation therapy (SBRT)
• Symptomatic CNS metastases (parenchymal or leptomeningeal) that are neurologically unstable or required an increasing dose of corticosteroids within 7 days prior to first dose of study drug
• Have current spinal cord compression (symptomatic or asymptomatic and detected by radiographic imaging). Patients with leptomeningeal disease and without cord compression is allowed.
• Malignancies other than NSCLC within 3 years prior to enrollment (except for adequately treated non-melanoma skin cancer, carcinoma in situ of the cervix, localized prostate cancer treated surgically with curative intent, which were allowed within 3 years)
• Women who are pregnant, lactating, or intending to become pregnant during the study.
• Patients that received monoclonal antibodies or had major surgery within 30 days of the first dose of brigatinib (Day 1, Cycle1) or anticipation of need for a major surgical procedure during the course of the study.
• History of idiopathic pulmonary fibrosis, pulmonary interstitial disease, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan.
• Have uncontrolled hypertension. Patients with hypertension should be under treatment on study entry to control blood pressure.
• Patients with active hepatitis B (chronic or acute; defined as having a positive hepatitis B surface antigen \[HBsAg\] test at screening) or hepatitis C.
• Patients with past hepatitis B virus (HBV) infection or resolved HBV infection (defined as the presence of hepatitis B core antibody \[HBcAb\] and absence of HBsAg) are eligible only if they are negative for HBV DNA.

Sponsors & Collaborators

• Fundación GECP: lead

Study Sites (15)

Complejo Hospitalario de A Coruña

A Coruña, A Coruña, 15006, Spain

Location

Hospital General de Alicante

Alicante, Alicante, 03010, Spain

Location

Hospital Regional Universitario de Málaga

Málaga, Andalusia, 29010, Spain

Location

Hospital Son Espases

Palma de Mallorca, Balearic Islands, 07120, Spain

Location

ICO Badalona

Badalona, Barcelona, 08916, Spain

Location

ICO Hospitalet

L'Hospitalet de Llobregat, Barcelona, 08908, Spain

Location

Hospital de la Santa Creu i Sant Pau

Barcelona, Catalonia, 08041, Spain

Location

Hospital Universitario Insular de Gran canaria

Las Palmas de Gran Canaria, Gran Canaria, 35016, Spain

Location

Hospital Universitario Fundación Jiménez Díaz

Madrid, Madrid, 28040, Spain

Location

Hospital Puerta de Hierro

Madrid, Madrid, 28222, Spain

Location

Hospital Clínico de Salamanca

Salamanca, Salamanca, 37007, Spain

Location

Hospital Universitari i Politécnic La Fe

Valencia, Valencia, 46009, Spain

Location

Hospital General de Valencia

Valencia, Valencia, 46014, Spain

Location

Hospital Universitario de Cruces

Barakaldo, Vizcaya, 48903, Spain

Location

Hospital Vall Hebron

Barcelona, 08035, Spain

Location

Related Links

• fundación GECP page

MeSH Terms

Conditions

Lung Neoplasms; Carcinoma, Non-Small-Cell Lung

Interventions

brigatinib

Condition Hierarchy (Ancestors)

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

Study Officials

• Mariano Provencio, MD

  Fundación GECP President

  PRINCIPAL INVESTIGATOR

Study Design

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

Model Details: Open-label, non-randomised, phase II, exploratory, multi-country and multi-centre clinical trial.

Study Record Dates

• First Submitted: January 7, 2020
• First Posted: January 10, 2020
• Study Start: May 4, 2020
• Primary Completion (Estimated): November 30, 2026
• Study Completion (Estimated): December 30, 2026
• Last Updated: February 4, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

ES (15)