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Clinical Trial 20388

Cancer Type: Thoracic
Study Type: Treatment
NCT#: NCT02706626

Phase: Phase II
Prinicipal Investigator: Eric Haura

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Overview

Study Title

Phase 2 Trial of Brigatinib After Treatment with Next-Generation ALK Inhibitors in Refractory ALK Rearranged NSCLC

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®).

Objective

Primary Objective: Estimate ORR (rate of CR+PR) of brigatinib in patients with ALK+ NSCLC who have progressed on next generation ALK inhibitors. Secondary Objectives: Further characterize treatment-related adverse events associated with brigatinib including at different doses in patients with ALK+ NSCLC. Estimate duration of response in patients with ALK+ NSCLC treated with brigatinib who have progressed after prior ALK inhibition. Estimate PFS in patients with ALK+ NSCLC treated with brigatinib who have progressed after prior ALK inhibition, Estimate intracranial and extra-cranial PFS in patients with ALK+ NSCLC treated with brigatinib who have progressed after prior ALK inhibition. Estimate OS in patients with ALK+ NSCLC treated with brigatinib who have progressed after prior ALK inhibition. Exploratory Objectives: Explore association between presence and/or type of mutation or mechanism of resistance at baseline and efficacy outcomes (ORR and PFS). Identify resistance mutations or other mechanisms of resistance after brigatinib by evaluating tumor samples at time of progression. Explore whether ctDNA from peripheral blood samples can identify development of resistance mutations. Estimate intracranial ORR in patients with ALK+ NSCLC treated with brigatinib who have progressed after prior ALK inhibition who have measurable CNS disease at baseline.

Treatments

Therapies

Medications

Brigatinib ()

Inclusion Criteria

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  • 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
  • 18 years of age or older
  • 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: (a) Whole brain radiation therapy (WBRT) within 3 months (b) Stereotactic radiosurgery (SRS) (c) 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. (d) 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. (e) 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 (f) 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 less 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 as defined per protocol.
  • At least 1 measurable lesion per RECIST version 1.1
  • Negative serum pregnancy test within 7 days of D1 of treatment in women of child bearing potential (WOCBP)
  • If fertile, willing to use highly effective form of contraception (as defined per protocol) during the dosing period and for at least 4 months after
  • Ability to provide signed informed consent and willing and able to comply with all study requirements
  • Other criteria apply

  • Exclusion Criteria

    > Exclusion Criteria for cohorts A, B, and C:

  • 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, as outlined per protocol.
  • 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 CNS metastases which require an increasing dose of corticosteroids within the last 2 weeks to remain asymptomatic.
  • 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.

  • If you are interested in learning more about clinical trials, our clinical trial navigators can discuss your options and recommend opportunities that may be suitable for you. Call 813-745-6100 or 1-800-679-0775 (toll-free) or submit a clinical trials inquiry form.