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A Study of Brigatinib in Participants With Anaplastic Lymphoma Kinase-Positive (ALK+), Advanced Non-Small-Cell Lung Cancer (NSCLC) Progressed on Alectinib or Ceritinib

NCT03535740

Description:

The primary purpose of this study is to determine the efficacy of brigatinib by confirmed objective response rate (ORR) by response evaluation criteria in solid tumors (Response Evaluation Criteria in Solid Tumors [RECIST]), in participants with ALK+ locally advanced or metastatic NSCLC whose disease has progressed on therapy with alectinib or ceritinib.

Related Conditions:
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Study of Brigatinib in Participants With Anaplastic Lymphoma Kinase-Positive (ALK+), Advanced Non-Small-Cell Lung Cancer (NSCLC) Progressed on Alectinib or Ceritinib
  • Official Title: Brigatinib in Patients With Anaplastic Lymphoma Kinase-Positive (ALK+), Advanced Non-Small-Cell Lung Cancer (NSCLC) Progressed on Alectinib or Ceritinib

Clinical Trial IDs

  • ORG STUDY ID: Brigatinib-2002
  • SECONDARY ID: 2018-000635-27
  • NCT ID: NCT03535740

Conditions

  • ALK-positive Advanced NSCLC

Interventions

DrugSynonymsArms
BrigatinibBrigatinib

Purpose

The primary purpose of this study is to determine the efficacy of brigatinib by confirmed objective response rate (ORR) by response evaluation criteria in solid tumors (Response Evaluation Criteria in Solid Tumors [RECIST]), in participants with ALK+ locally advanced or metastatic NSCLC whose disease has progressed on therapy with alectinib or ceritinib.

Detailed Description

      The drug being tested in this study is called brigatinib (AP26113). Brigatinib is being
      tested to treat people who have anaplastic lymphoma kinase-positive (ALK+), advanced
      non-small-cell lung cancer (NSCLC).

      The study will enroll approximately 103 patients. Participants will be assigned to the
      treatment group:

      • Brigatinib

      All participants will be asked to take brigatinib 90 mg tablet in lead-in period for 7 days,
      followed by brigatinib 180 mg at the same time each day throughout the study.

      This multicenter trial will be conducted worldwide. The overall time to participate in this
      study is approximately 5 years, but the total sample size and study duration may be adjusted
      according to preliminary data from interim analysis. Participants will make multiple visits
      to the clinic, and 30 days after last dose of study drug for a follow-up assessment.
    

Trial Arms

NameTypeDescriptionInterventions
BrigatinibExperimentalBrigatinib 90 mg, tablets, orally, once daily for 7 days, followed by Brigatinib 180 mg, tablets, orally, once daily for until objective disease progression per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, as assessed by the investigator, or intolerable toxicity.
  • Brigatinib

Eligibility Criteria

        Inclusion Criteria:

          1. Have histologically or cytologically confirmed stage IIIB (locally advanced or
             recurrent and not a participant for curative therapy) or stage IV non-small-cell lung
             cancer (NSCLC).

          2. Must meet both of the following 2 criteria:

               1. Have documentation of anaplastic lymphoma kinase (ALK) rearrangement by a
                  positive result from any laboratory test® approved by the food and drug
                  administration (FDA) or Have documented ALK rearrangement by a different test
                  (non-FDA-approved local lab tests) and have provided tumor sample to the central
                  laboratory. (Note: Central laboratory ALK rearrangement testing results are not
                  required to be obtained before randomization.)

               2. Had been on any one of the ALK tyrosine kinase inhibitor (TKIs) (alectinib,
                  ceritinib, crizotinib) for at least 12 weeks before progression.

          3. Had progressive disease (PD) while on alectinib or ceritinib

          4. Had alectinib or ceritinib as the most recent ALK inhibitor therapy.

          5. Have at least 1 measurable lesion per response evaluation criteria in solid tumors
             (RECIST) version 1.1 as assessed by the investigator.

          6. Had recovered from toxicities related to prior anticancer therapy to national cancer
             institute common terminology criteria for adverse events (NCI CTCAE), version 4.03,
             Grade =1. (Note: Treatment-related alopecia or peripheral neuropathy that are Grade >1
             are allowed if deemed irreversible.) and have adequate major organ functions.

          7. Have a life expectancy of ≥3 months.

        Exclusion Criteria:

          1. Had received any prior ALK-targeted TKI other than crizotinib, alectinib, or
             ceritinib.

          2. Had received both alectinib and ceritinib.

          3. Had previously received more than 3 regimens of systemic anticancer therapy for
             locally advanced or metastatic disease.

          4. Had symptomatic brain metastasis (parenchymal or leptomeningeal). Participants with
             asymptomatic brain metastasis or who have stable symptoms that did not require an
             increased dose of corticosteroids to control symptoms in the past 7 days before the
             first dose of brigatinib may be enrolled.

          5. Had current spinal cord compression (symptomatic or asymptomatic and detected by
             radiographic imaging). Participants with leptomeningeal disease and without cord
             compression are allowed.

          6. Had a cerebrovascular accident or transient ischemic attack within 6 months before
             first dose of brigatinib.

          7. Had an ongoing or active infection, including, but not limited to, the requirement for
             intravenous antibiotics.

          8. Had malabsorption syndrome or other gastrointestinal (GI) illness that could affect
             oral absorption of brigatinib.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Confirmed Objective Response Rate (ORR) Using RECIST v1.1 as Assessed by the Independent Review Committee (IRC)
Time Frame:Every 8 weeks for 52 weeks and every 12 weeks after, until the radiological disease progression (approximately 5 years)
Safety Issue:
Description:Confirmed ORR is defined as the percentage of the participants who are confirmed to have achieved complete response (CR) or partial response (PR), per RECIST version 1.1 (confirmed ≥4 weeks after initial response), after the initiation of study treatment. CR: disappearance of all extranodal target lesions and all pathological lymph nodes must have decreased to <10 mm in short axis and PR: at least a 30% decrease in the sum of the longest diameters (SLD) of target lesions taking as reference the baseline sum diameters.

Secondary Outcome Measures

Measure:Confirmed ORR Using RECIST v1.1 as Assessed by the Investigator
Time Frame:Every 8 weeks for 52 weeks and every 12 weeks after, until the radiological disease progression (approximately 5 years)
Safety Issue:
Description:Confirmed ORR is defined as the percentage of the participants who are confirmed to have achieved CR or PR, per RECIST version 1.1 (confirmed ≥4 weeks after initial response), after the initiation of study treatment. CR: disappearance of all extranodal target lesions and all pathological lymph nodes must have decreased to <10 mm in short axis and PR: at least a 30% decrease in the SLD of target lesions taking as reference the baseline sum diameters.
Measure:Duration of Response (DOR) as Assessed by the Investigator and IRC
Time Frame:Every 8 weeks for 52 weeks and every 12 weeks after, until the radiological disease progression (approximately 5 years)
Safety Issue:
Description:DOR is defined as the time interval from the time that the measurement criteria are first met for CR or PR until the first date that the progressive disease (PD) is objectively documented, or death. CR: disappearance of all extranodal target lesions and all pathological lymph nodes must have decreased to <10 mm in short axis. PR: at least a 30% decrease in the SLD of target lesions taking as reference the baseline sum diameters. PD: SLD increased by at least 20% from the smallest value on study (including baseline, if that is the smallest). SLD must also demonstrate an absolute increase of at least 5 mm. (2 lesions increasing from, for example, 2 mm to 3 mm, does not qualify).
Measure:Progression-Free Survival (PFS) as Assessed by the Investigator and IRC
Time Frame:Every 8 weeks for 52 weeks and every 12 weeks after, until the radiological disease progression (approximately 5 years)
Safety Issue:
Description:PFS is defined as the time interval from the date of the first dose of the study treatment until the first date at which disease progression is objectively documented, or death due to any cause, whichever occurs first. PFS will be censored for participants without documented disease progression or death.
Measure:Disease Control Rate (DCR) as Assessed by the Investigator and IRC
Time Frame:Every 8 weeks for 52 weeks and every 12 weeks after, until the radiological disease progression (approximately 5 years)
Safety Issue:
Description:DCR is defined as the percentage of participants who have achieved CR, PR or stable disease (SD) (in the case of SD, measurements must have met the SD criteria at least once after study entry at a minimum interval of 6 weeks) after the initiation of study treatment. CR: disappearance of all extranodal target lesions and all pathological lymph nodes must have decreased to <10 mm in short axis. PR: at least a 30% decrease in the SLD of target lesions taking as reference the baseline sum diameters. SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD.
Measure:Time to Response as Assessed by the Investigator and IRC
Time Frame:Every 8 weeks for 52 weeks and every 12 weeks after, until the radiological disease progression (approximately 5 years)
Safety Issue:
Description:Time to response is defined as the time interval from the date of the first dose of the study treatment until the initial observation of CR or PR. CR: disappearance of all extranodal target lesions and all pathological lymph nodes must have decreased to <10 mm in short axis. PR: at least a 30% decrease in the SLD of target lesions taking as reference the baseline sum diameters.
Measure:Confirmed Intracranial Objective Response Rate (iORR) in Participants With Brain Metastases at Baseline, as Assessed by the IRC
Time Frame:Every 8 weeks for 52 weeks and every 12 weeks after, until the radiological disease progression (approximately 5 years)
Safety Issue:
Description:Confirmed iORR is defined as the proportion of the participants who have achieved CR or PR in the brain per a modification of RECIST version 1.1, after the initiation of study treatment, in participants with intracranial brain metastases at baseline. CR: disappearance of all extranodal target lesions and all pathological lymph nodes must have decreased to <10 mm in short axis. or partial response or PR: at least a 30% decrease in the SLD of target lesions taking as reference the baseline sum diameters.
Measure:Duration of Intracranial Response in Participants With Brain Metastases at Baseline, as Assessed by the IRC
Time Frame:Every 8 weeks for 52 weeks and every 12 weeks after, until the radiological disease progression (approximately 5 years)
Safety Issue:
Description:Duration of intracranial response is defined as the time interval from the time that the measurement criteria are first met for CR or PR until the first date that PD (including baseline, if that is the smallest). SLD must also demonstrate an absolute increase of at least 5 mm. (2 lesions increasing from, for example, 2 mm to 3 mm, does not qualify) in the brain is objectively documented or death, in participants with intracranial metastases at baseline. CR: disappearance of all extranodal target lesions and all pathological lymph nodes must have decreased to <10 mm in short axis. or partial response or PR: at least a 30% decrease in the SLD of target lesions taking as reference the baseline sum diameters in the brain. PD: SLD increased by at least 20% from the smallest value on study.
Measure:Intracranial Progression-Free Survival (iPFS) in Participants With Brain Metastases at Baseline, as Assessed by the IRC
Time Frame:Every 8 weeks for 52 weeks and every 12 weeks after, until the radiological disease progression (approximately 5 years)
Safety Issue:
Description:iPFS is defined as the time interval from the date of the first dose of the study treatment until the first date at which intracranial brain disease progression is objectively documented, or death due to any cause, whichever occurs first, in participants with intracranial metastases at enrollment. iPFS will be censored for participants without documented intracranial disease progression or death.
Measure:Overall Survival (OS)
Time Frame:Every 8 weeks for 52 weeks and every 12 weeks after, until the radiological disease progression (approximately 5 years)
Safety Issue:
Description:OS is defined as the time interval from the date of the first dose of the study treatment until death due to any cause. It will be censored on the date of last contact for those participants who are alive.
Measure:Number of Participants With One or More Treatment-emergent Adverse Event (TEAE)
Time Frame:First dose of study drug up to 30 days after last dose (approximately 5 years)
Safety Issue:
Description:An adverse event (AE) means any untoward medical occurrence in a participant administered a pharmaceutical product; the untoward medical occurrence does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product whether or not it is related to the medicinal product. This includes any newly occurring event, or a previous condition that has increased in severity or frequency since the administration of study drug.
Measure:Health-Related Quality of Life (HRQOL) from European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Score
Time Frame:First dose of study drug up to 30 days after last dose (approximately 5 years)
Safety Issue:
Description:EORTC QLQ-C30 incorporates 5 functional scales (physical functioning, role functioning, emotional functioning, cognitive functioning, and social functioning), 1 global health status scale, 3 symptom scales (fatigue, nausea and vomiting, and pain), and 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). EORTC QLQ-C30 contains 28 questions (4-point scale where 1=Not at all [best] to 4=Very Much [worst]) and 2 questions (7-point scale where 1=Very poor [worst] to 7= Excellent [best]). Raw scores are converted into scale scores ranging from 0 to 100. For the functional scales and the global health status scale, higher scores represent better quality of life (QOL); for the symptom scales, lower scores represent better QOL.
Measure:HRQOL from EORTC QLQ- Lung Cancer (LC) 13
Time Frame:First dose of study drug up to 30 days after last dose (approximately 5 years)
Safety Issue:
Description:HRQOL scores will be assessed with EORTC, its lung cancer module QLQ-LC13. QLQ-LC13 contains 13 questions assessing lung cancer-associated symptoms (cough, hemoptysis, dyspnea, and site-specific pain), treatment-related side effects (sore mouth, dysphagia, peripheral neuropathy, and alopecia), and use of pain medication. Scale score range: 0 to 100. Higher symptom score = greater degree of symptom severity.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Ariad Pharmaceuticals

Trial Keywords

  • Drug Therapy

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