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Trial record 1 of 2 for:    ALTA 1L
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ALTA-1L Study: A Phase 3 Study of Brigatinib Versus Crizotinib in ALK-positive Advanced Non-Small Cell Lung Cancer Patients (ALTA-1L)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Ariad Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT02737501
First received: March 30, 2016
Last updated: September 5, 2017
Last verified: September 2017
  Purpose
A Phase 3 Multicenter Open-label Study of Brigatinib (AP26113) versus Crizotinib in ALK-positive Advanced Lung Cancer Patients

Condition Intervention Phase
Non-small Cell Lung Cancer Lung Cancer Advanced Malignancies Carcinoma Drug: Brigatinib Drug: Xalkori (crizotinib) Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 3 Multicenter Open-label Study of Brigatinib (AP26113) Versus Crizotinib in Patients With ALK-positive Advanced Lung Cancer

Resource links provided by NLM:


Further study details as provided by Ariad Pharmaceuticals:

Primary Outcome Measures:
  • Progression-free survival (PFS) as assessed by a blinded Independent Review Committee (bIRC) [ Time Frame: At least 36 months ]

Secondary Outcome Measures:
  • Objective response rate (ORR) [ Time Frame: At least 36 months ]
    Defined as the proportion of the patients who are confirmed to have achieved CR or PR using RECIST v. 1.1 criteria.

  • Intracranial ORR [ Time Frame: At least 36 months ]
    Defined as the proportion of the patients who have achieved CR or PR in the CNS.

  • Intracranial PFS [ Time Frame: At least 36 months ]
    Defined as the time from randomization until first CNS disease progression is documented, or death due to any cause.

  • Overall Survival (OS) [ Time Frame: At least 36 months. ]
    Defined as the time from randomization until death due to any cause.

  • Health-related quality of life (HRQoL) [ Time Frame: Until 30 days after the last dose of study treatment. ]
    Defined as the perceived quality of the patient's life, which includes self-reported multidimensional measures of physical and mental health.

  • Percentage of patients with adverse events [ Time Frame: Until at least 30 days after the last dose of study treatment. ]
    To evaluate the safety and tolerability of brigatinib in the Intention to Treat (ITT) population. Measured by routine physical and laboratory evaluations, ECG, and adverse event (AE) monitoring.

  • Steady state pharmacokinetic (PK) parameter: Maximum Plasma Concentration [Cmax] [ Time Frame: Up to 28 months. ]
    PK samples will be taken to assess limited elements of PK in the Treated population.

  • Steady state pharmacokinetic (PK) parameter: Minimum plasma concentration [Cmin] [ Time Frame: Up to 28 months. ]
    PK samples will be taken to assess limited elements of PK in the Treated population.

  • Steady state pharmacokinetic (PK) parameter: Area Under the Curve [AUC] [ Time Frame: Up to 28 months. ]
    PK samples will be taken to assess limited elements of PK in the Treated population.

  • Steady state pharmacokinetic (PK) parameter: Time to maximum plasma concentration (Tmax) [ Time Frame: Up to 28 months. ]
    PK samples will be taken to assess limited elements of PK in the Treated population.

  • Steady state pharmacokinetic (PK) parameter: Apparent oral clearance [CL/F] [ Time Frame: Up to 28 months. ]
    PK samples will be taken to assess limited elements of PK in the Treated population.


Enrollment: 270
Actual Study Start Date: April 30, 2016
Estimated Study Completion Date: April 30, 2021
Estimated Primary Completion Date: April 30, 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Brigatinib
Brigatinib will be administered orally to eligible patients with locally advanced or metastatic ALK+ NSCLC naïve to ALK inhibitors at a dose of 90 mg QD for 7 days, then 180 mg QD, continuously, with or without food until disease progression, unacceptable toxicity, withdrawal of consent or death.
Drug: Brigatinib
Brigatinib will be administered orally to eligible patients with locally advanced or metastatic ALK+ NSCLC naïve to ALK inhibitors at a dose of 90 mg QD for 7 days, then 180 mg QD, continuously, until disease progression, unacceptable toxicity, withdrawal of consent or death.
Active Comparator: Crizotinib
Crizotinib will be administered to eligible patients with locally advanced or metastatic ALK+ NSCLC naïve to ALK inhibitors as 250 mg orally BID, with or without food until disease progression, unacceptable toxicity, withdrawal of consent or death.
Drug: Xalkori (crizotinib)
Crizotinib will be administered to eligible patients with locally advanced or metastatic ALK+ NSCLC naïve to ALK inhibitors as 250 mg orally BID, until disease progression, unacceptable toxicity, withdrawal of consent or death.
Other Name: Crizotinib

Detailed Description:
The purpose of this phase III, randomized, open-label, comparative, multicenter, international study is to compare the efficacy and safety of brigatinib to that of crizotinib in anaplastic lymphoma kinase (ALK)-positive locally advanced or metastatic non-small cell lung cancer (NSCLC) patients who have not previously been treated with an ALK inhibitor. Participants will be randomized in a 1:1 ratio to receive either brigatinib, 90 milligrams (mg) orally once daily (QD) for 7 days, then a 180 mg orally QD, or crizotinib, 250 mg orally twice daily (BID). Participants will receive treatment until disease progression, intolerable toxicity, consent withdrawal, or death. The total estimated duration of the study is at least 5 years, including 2 years to accrue patients, with at least 3 years for treatment and follow-up.
  Eligibility

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

Inclusion Criteria:

  1. Have histologically or cytologically confirmed stage IIIB (and not a candidate for definitive multimodality therapy) or stage IV NSCLC.
  2. Must have documented ALK rearrangement.
  3. Have sufficient tumor tissue available for central analysis.
  4. Have at least 1 measurable (i.e., target) lesion per RECIST v1.1.
  5. Recovered from toxicities related to prior anticancer therapy to NCI CTCAE v 4.0 grade ≤1.
  6. Are a male or female patient ≥18 years old.
  7. Have adequate organ function, as defined by the study protocol.
  8. Have Eastern Cooperative Oncology Group (ECOG) performance status ≤2.
  9. Have normal QT interval on screening ECG evaluation, defined as QT interval corrected (Fridericia) (QTcF) of ≤450 milliseconds (msec) in males or ≤470 msec in females.
  10. For female patients of childbearing potential, have a negative pregnancy test documented prior to randomization.
  11. For female and male patients who are fertile, agree to use a highly effective form of contraception, as defined by the study protocol.
  12. Provide signed and dated informed consent indicating that the patient has been informed of all pertinent aspects of the study, including the potential risks, and is willingly participating.
  13. Have the willingness and ability to comply with scheduled visit and study procedures.

Exclusion Criteria:

  1. Previously received an investigational antineoplastic agent for NSCLC.
  2. Previously received any prior TKI, including ALK-targeted TKIs.
  3. Previously received more than 1 regimen of systemic anticancer therapy for locally advanced or metastatic disease.
  4. Received chemotherapy or radiation within 14 days of first dose of study drug, except stereotactic radiosurgery (SRS) or stereotactic body radiation therapy (SBRT).
  5. Received anti-neoplastic monoclonal antibodies within 30 days of the first dose of study drug.
  6. Had major surgery within 30 days of the first dose of study drug, minor surgical procedures such as catheter placement or minimally invasive biopsies are allowed.
  7. Have been diagnosed with another primary malignancy other than NSCLC, except for adequately treated non-melanoma skin cancer or cervical cancer in situ; definitively treated non-metastatic prostate cancer; or patients with another primary malignancy who are definitively relapse-free with at least 3 years elapsed since the diagnosis of the other primary malignancy.
  8. Have symptomatic CNS metastases (parenchymal or leptomeningeal) at screening or asymptomatic disease requiring an increasing dose of corticosteroids to control symptoms within 7 days prior to randomization.
  9. Have current spinal cord compression (symptomatic or asymptomatic and detected by radiographic imaging). Patients with leptomeningeal disease and without cord compression are allowed.
  10. Be pregnant, planning a pregnancy, or breastfeeding
  11. Have significant, uncontrolled, or active cardiovascular disease, as defined by the study protocol.
  12. Have uncontrolled hypertension.
  13. Have a history or the presence at baseline of pulmonary interstitial disease, drug-related pneumonitis, or radiation pneumonitis.
  14. Have an ongoing or active infection.
  15. Have a known history of human immunodeficiency virus (HIV) infection.
  16. Have a known or suspected hypersensitivity to brigatinib or its excipients and/or crizotinib or its excipients.
  17. Have malabsorption syndrome or other gastrointestinal (GI) illness or condition.
  18. Have any condition or illness that, in the opinion of the investigator, would compromise patient safety or interfere with the evaluation of the study drug.
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02737501

  Show 124 Study Locations
Sponsors and Collaborators
Ariad Pharmaceuticals
  More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Ariad Pharmaceuticals
ClinicalTrials.gov Identifier: NCT02737501     History of Changes
Other Study ID Numbers: AP26113-13-301
Study First Received: March 30, 2016
Last Updated: September 5, 2017

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Ariad Pharmaceuticals:
Non-small cell lung cancer
Non-small cell lung carcinoma
Epithelial lung cancer
Squamous cell carcinoma
Large cell carcinoma
Adenocarcinoma
Carcinoma
Anaplastic Lymphoma Kinase (ALK)
Advanced Cancers
Brigatinib
AP26113

Additional relevant MeSH terms:
Carcinoma
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Crizotinib
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 21, 2017