Clinical Utility of Liquid Biopsy as a Tool to Assess the Evolution of Brigatinib Treated Patients With Non-small Cell Lung Cancer With EML4-ALK Translocation: an Exploratory Study
Overview
- Phase
- Phase 2
- Intervention
- Brigatinib
- Conditions
- Lung Cancer
- Sponsor
- Fundación GECP
- Enrollment
- 33
- Locations
- 15
- Primary Endpoint
- Overall response rate (ORR)
- Status
- Active, not recruiting
- Last Updated
- 2 months ago
Overview
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •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
Exclusion Criteria
- •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.
Arms & Interventions
Experimental: Brigatinib Arm
Brigatinib 90 mg for the first 7 days and then 180 mg daily thereafter for QW4 cycles of duration (28 days +- 3 days)
Intervention: Brigatinib
Outcomes
Primary Outcomes
Overall response rate (ORR)
Time Frame: From date of randomization until the date of first documented progression or date of death, whichever came first, assessed up to 60 months
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.
Secondary Outcomes
- 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.)
- Time on treatment (TTR)(From date of the start of treatment until first objective tumour response observed (partial or complete according RECIST v1.1), assessed up to 60 months.)