Clinical Trials /

An Efficacy Study Comparing Brigatinib Versus Alectinib in Advanced Anaplastic Lymphoma Kinase-Positive Non-Small-Cell Lung Cancer Participants Who Have Progressed on Crizotinib

NCT03596866

Description:

The purpose of this study is to compare the efficacy of brigatinib versus alectinib in participants with anaplastic lymphoma kinase-positive (ALK+) locally advanced or metastatic non-small-cell lung cancer (NSCLC) who have progressed on crizotinib as evidenced by progression free survival as assessed by a blinded independent review committee (BIRC) utilizing response evaluation criteria in solid tumors (RECIST) v1.1.

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

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: An Efficacy Study Comparing Brigatinib Versus Alectinib in Advanced Anaplastic Lymphoma Kinase-Positive Non-Small-Cell Lung Cancer Participants Who Have Progressed on Crizotinib
  • Official Title: A Phase 3 Randomized Open-label Study of Brigatinib (Alunbrig®) Versus Alectinib (Alecensa®) in Advanced Anaplastic Lymphoma Kinase-Positive Non Small-Cell Lung Cancer Patients Who Have Progressed on Crizotinib (Xalkori®)

Clinical Trial IDs

  • ORG STUDY ID: Brigatinib-3001
  • SECONDARY ID: 2018-001957-29
  • NCT ID: NCT03596866

Conditions

  • ALK-positive Advanced NSCLC

Interventions

DrugSynonymsArms
BrigatinibAlunbrigBrigatinib
AlectinibAlecensaAlectinib

Purpose

The purpose of this study is to compare the efficacy of brigatinib versus alectinib in participants with anaplastic lymphoma kinase-positive (ALK+) locally advanced or metastatic non-small-cell lung cancer (NSCLC) who have progressed on crizotinib as evidenced by progression free survival as assessed by a blinded independent review committee (BIRC) utilizing response evaluation criteria in solid tumors (RECIST) v1.1.

Detailed Description

      The drug being tested in this study is called brigatinib. Brigatinib has been demonstrated to
      benefit people with ALK-positive NSCLC.

      The comparator drug is called alectinib. Alectinib has been demonstrated to benefit people
      with ALK-positive NSCLC. Both drugs belong to a class of drugs called ALK inhibitors. Both
      drugs are taken by mouth. Both drugs are approved by the US FDA.

      The study will enroll approximately 246 patients. Participants will be randomly assigned (by
      chance, like flipping a coin) in 1:1 ratio to one of the two treatment groups:

      Brigatinib Alectinib

      All participants will be asked to take brigatinib or alectinib at the same time each day
      throughout the study.

      This multi-center trial will be conducted worldwide. The overall time to participate in this
      study is 5 years. 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 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
AlectinibActive ComparatorAlectinib 600 mg, capsules, orally twice daily until objective disease progression per RECIST version 1.1, as assessed by the investigator, or intolerable toxicity.
  • Alectinib

Eligibility Criteria

        Inclusion Criteria:

          1. Have Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.

          2. Have histologically or cytologically confirmed stage IIIB (locally advanced or
             recurrent) or stage IV non-small cell lung cancer (NSCLC).

          3. Must meet one of the following criteria:

               1. Have documentation of anaplastic lymphoma kinase (ALK) rearrangement by a
                  positive result from the Vysis ALK Break-Apart fluorescence in situ hybridization
                  (FISH) Probe Kit or the Ventana ALK (D5F3) CDx Assay or Foundation Medicine's
                  FoundationOne CDx.

               2. Have documented ALK rearrangement by a different test and be able to provide
                  tumor sample to the central laboratory. (Note: central laboratory ALK
                  rearrangement testing results are not required to be obtained before
                  randomization).

          4. Had progressive disease (PD) while on crizotinib, as assessed by the investigator or
             treating physician. (Note: crizotinib does not need to be the last therapy a
             participant received. The participant may have received chemotherapy as his/her last
             therapy).

          5. Treatment with crizotinib for at least 4 weeks before progression.

          6. Have had no other ALK inhibitor other than crizotinib.

          7. Have had no more than 2 prior regimens of systemic anticancer therapy in the locally
             advanced or metastatic setting. Note: a systemic anticancer therapy regimen will be
             counted if it is administered over at least 1 cycle. A new antineoplastic agent used
             as maintenance therapy will be counted as a new regimen. Neoadjuvant or adjuvant
             systemic anticancer therapy will be counted as a prior regimen if disease
             progression/recurrence occurred within 12 months upon completion of this neoadjuvant
             or adjuvant therapy.

          8. Have at least 1 measurable (ie, target) lesion per response evaluation criteria in
             solid tumors (RECIST) v1.1.

          9. Have recovered from toxicities related to prior anticancer therapy to national cancer
             institute common terminology criteria for adverse events (NCI CTCAE) v4.03 grade ≤1.
             (Note: treatment-related alopecia or peripheral neuropathy that are grade >1 are
             allowed, if deemed irreversible).

         10. Have adequate organ function, as determined by:

               1. Total bilirubin ≤1.5 times the upper limit of normal (ULN).

               2. Estimated glomerular filtration rate ≥30 mL/minute/1.73 m2, using the
                  modification of diet in renal disease equation.

               3. Alanine aminotransferase (ALT)/aspartate aminotransferase (AST) ≤2.5 × ULN; ≤5 ×
                  ULN is acceptable if liver metastases are present.

               4. Serum lipase ≤1.5 × ULN.

               5. Platelet count ≥75 ×109/L.

               6. Hemoglobin ≥9 g/dL.

               7. Absolute neutrophil count ≥1.5 × 109/L.

         11. Suitable venous access for study-required blood sampling (ie, including PK and
             laboratory safety tests).

        Exclusion Criteria:

          1. Had participated in the control (crizotinib) arm of Study AP26113-13-301 (ALTA 1L).

          2. Had received crizotinib within 7 days of randomization.

          3. Have a history or presence at baseline of pulmonary interstitial disease, drug related
             pneumonitis, or radiation pneumonitis.

          4. Have uncontrolled hypertension. Participants with hypertension should be under
             treatment for control of blood pressure upon study entry.

          5. Had Received systemic treatment with strong cytochrome P-450 (CYP) 3A inhibitors,
             strong CYP3A inducers, or moderate CYP3A inducers within 14 days before randomization.

          6. Treatment with any investigational systemic anticancer agents within 14 days or 5
             half-lives, whichever is longer, before randomization.

          7. Had received chemotherapy or radiation therapy within 14 days of randomization except
             for stereotactic radiosurgery (SRS) or stereotactic body radiation therapy.

          8. Had received antineoplastic monoclonal antibodies within 30 days of randomization.

          9. Had major surgery within 30 days of randomization. Minor surgical procedures, such as
             catheter placement or minimally invasive biopsies, are allowed.

         10. Have symptomatic CNS metastases (parenchymal or leptomeningeal) at screening
             (participants with asymptomatic brain metastases or participants who have stable
             symptoms and did not require an increased dose of corticosteroids to control symptoms
             within 7 days before randomization will be enrolled). Note: If a participant has
             worsening neurological symptoms or signs due to CNS metastasis, the participant needs
             to complete local therapy and be neurologically stable (with no requirement for an
             increasing dose of corticosteroids or use of anticonvulsants) for 7 days before
             randomization.

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

         12. Have significant, uncontrolled, or active cardiovascular disease, specifically
             including, but not restricted to the following:

               1. Myocardial infarction within 6 months before randomization.

               2. Unstable angina within 6 months before randomization.

               3. New York Heart Association Class III or IV heart failure within 6 months before
                  randomization.

               4. History of clinically significant atrial arrhythmia (including clinically
                  significant bradyarrhythmia), as determined by the treating physician.

               5. Any history of clinically significant ventricular arrhythmia.

         13. Had cerebrovascular accident or transient ischemic attack within 6 months before first
             dose of study drug.

         14. Have malabsorption syndrome or other gastrointestinal illness or condition that could
             affect oral absorption of the study drug.

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

         16. Have a known history of HIV infection. Testing is not required in the absence of
             history.

         17. Known hepatitis B surface antigen-positive, or known or suspected active hepatitis C
             infection.

         18. Have a known or suspected hypersensitivity to brigatinib or alectinib or their
             excipients.

         19. Life-threatening illness unrelated to cancer.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression-Free Survival (PFS) as Assessed by Blinded Independent Review Committee (BIRC) per RECIST v1.1
Time Frame:Up to 5 years
Safety Issue:
Description:PFS is defined as the time interval from the date of randomization until the first date at which disease progression is objectively documented via RECIST v1.1, or death due to any cause, whichever occurs first, in the full analysis set. Disease progression was at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since the treatment started or the appearance of 1 or more new lesions or the appearance of 1 or more new lesions and/or unequivocal progression of existing non-target lesions.

Secondary Outcome Measures

Measure:Intracranial Progression-Free Survival (iPFS) as Assessed by BIRC per modified RECIST v1.1
Time Frame:Up to 5 years
Safety Issue:
Description:iPFS is defined as the time interval from the date of randomization until the first date at which intracranial disease progression is objectively documented via a modification of RECIST v1.1, or death due to any cause, whichever occurs first. Disease progression was at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since the treatment started or the appearance of 1 or more new lesions or the appearance of 1 or more new lesions and/or unequivocal progression of existing non-target lesions.
Measure:Overall Survival (OS)
Time Frame:Up to 9 years
Safety Issue:
Description:OS is defined as the time interval from the date of randomization until death due to any cause.
Measure:Objective Response Rate (ORR) as Assessed by Investigator and BIRC per RECIST v1.1
Time Frame:Up to 5 years
Safety Issue:
Description:ORR is defined as the proportion of the participants who are confirmed to have achieved complete response (CR) or partial response (PR), using RECIST v1.1 after the initiation of study treatment. CR is defined as disappearance of all extranodal target lesions. All pathological lymph nodes must have decreased to <10 mm in short axis. PR is defined as at least a 30% decrease in the sum of the longest diameters (SLD) of target lesions, taking as reference the baseline sum diameters.
Measure:Time to Response as Assessed by Investigator and BIRC
Time Frame:Up to 5 years
Safety Issue:
Description:Time to response is defined as the time interval from randomization until the initial observation of CR or PR. CR is defined as disappearance of all extranodal target lesions. All pathological lymph nodes must have decreased to <10 mm in short axis. PR is defined as 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 Investigator and BIRC
Time Frame:Up to 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 (whichever is first recorded) until the first date that the PD is objectively documented or death. CR is defined as disappearance of all extranodal target lesions. All pathological lymph nodes must have decreased to <10 mm in short axis. PR is defined as at least a 30% decrease in the SLD of target lesions, taking as reference the baseline sum diameters. Progressive disease (PD) is defined as 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) is objectively documented or death.
Measure:Intracranial Objective Response Rate (iORR) as Assessed by BIRC per Modified RECIST v1.1
Time Frame:Up to 5 years
Safety Issue:
Description:iORR is defined as the proportion of the participants who have achieved CR or PR in the CNS per a modification RECIST v1.1 after the initiation of study treatment in participant with CNS metastases at enrollment. CR is defined as disappearance of all extranodal target lesions. All pathological lymph nodes must have decreased to <10 mm in short axis. PR is defined as at least a 30% decrease in the SLD of target lesions, taking as reference the baseline sum diameters in the central nervous system (CNS).
Measure:Intracranial Duration of Response (iDOR) as Assessed by the BIRC per Modified RECIST v1.1
Time Frame:Up to 5 years
Safety Issue:
Description:iDOR is defined as the time interval from the time that the measurement criteria are first met for CR or PR in the CNS (whichever is first recorded) until the first date that the PD in the CNS is objectively documented or death. CR is defined as disappearance of all extranodal target lesions. All pathological lymph nodes must have decreased to <10 mm in short axis. PR is defined as at least a 30% decrease in the SLD of target lesions, taking as reference the baseline sum diameters. PD is defined as 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) is objectively documented or death.
Measure:Health-Related Quality of Life (HRQOL) from European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30 v3.0) Score
Time Frame:First dose of study drug up to 30 days after last dose (approximately 9 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 9 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 3
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Ariad Pharmaceuticals

Trial Keywords

  • Drug Therapy

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