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Trial record 24 of 39 for:    ALECTINIB

A Study of Brigatinib in Participants With Anaplastic Lymphoma Kinase-Positive (ALK+), Advanced Non-Small-Cell Lung Cancer (NSCLC) Progressed on Alectinib or Ceritinib (ALTA-2)

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ClinicalTrials.gov Identifier: NCT03535740
Recruitment Status : Recruiting
First Posted : May 24, 2018
Last Update Posted : October 11, 2019
Sponsor:
Information provided by (Responsible Party):
Takeda ( Ariad Pharmaceuticals )

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
ALK-positive Advanced NSCLC Drug: Brigatinib Phase 2

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 103 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Brigatinib in Patients With Anaplastic Lymphoma Kinase-Positive (ALK+), Advanced Non-Small-Cell Lung Cancer (NSCLC) Progressed on Alectinib or Ceritinib
Actual Study Start Date : January 31, 2019
Estimated Primary Completion Date : December 18, 2019
Estimated Study Completion Date : April 22, 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Brigatinib
Brigatinib 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.
Drug: Brigatinib
Brigatinib Tablets




Primary Outcome Measures :
  1. 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) ]
    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 :
  1. 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) ]
    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.

  2. 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) ]
    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).

  3. 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) ]
    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.

  4. 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) ]
    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.

  5. 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) ]
    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.

  6. 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) ]
    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.

  7. 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) ]
    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.

  8. 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) ]
    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.

  9. Overall Survival (OS) [ Time Frame: Every 8 weeks for 52 weeks and every 12 weeks after, until the radiological disease progression (approximately 5 years) ]
    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.

  10. 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) ]
    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.

  11. 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) ]
    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.

  12. 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) ]
    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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03535740


Contacts
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Contact: Takeda Study Registration Call Center +1-866-835-2233 globaloncologymedinfo@takeda.com

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Sponsors and Collaborators
Ariad Pharmaceuticals
Investigators
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Study Director: Medical Director Clinical Science Ariad Pharmaceuticals

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Responsible Party: Ariad Pharmaceuticals
ClinicalTrials.gov Identifier: NCT03535740     History of Changes
Other Study ID Numbers: Brigatinib-2002
2018-000635-27 ( EudraCT Number )
NL66462.078.18 ( Registry Identifier: CCMO )
First Posted: May 24, 2018    Key Record Dates
Last Update Posted: October 11, 2019
Last Verified: October 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Takeda makes patient-level, de-identified data sets and associated documents available for all interventional studies after applicable marketing approvals and commercial availability have been received (or program is completely terminated), an opportunity for the primary publication of the research and final report development has been allowed, and other criteria have been met as set forth in Takeda's Data Sharing Policy (see www.TakedaClinicalTrials.com for details). To obtain access, researchers must submit a legitimate academic research proposal for adjudication by an independent review panel, who will review the scientific merit of the research and the requestor's qualifications and conflict of interest that can result in potential bias. Once approved, qualified researchers who sign a data sharing agreement are provided access to these data in a secure research environment.

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Takeda ( Ariad Pharmaceuticals ):
Drug Therapy
Additional relevant MeSH terms:
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Carcinoma, Non-Small-Cell Lung
Neoplasms
Carcinoma, Bronchogenic
Bronchial Neoplasms
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Ceritinib
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action