Clinical Trials /

Study of Lorlatinib In Participants With Anaplastic Lymphoma Kinase (ALK) -Positive NSCLC

NCT04362072

Description:

A Phase 4 study to assess Overall and Intracranial Response Rate of single-agent lorlatinib in participants with advanced ALK-positive NSCLC whose disease has progressed on alectinib or ceritinib as the first ALK tyrosine kinase inhibitor (TKI)therapy.

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

Recruiting

Phase:

Phase 4

Trial Eligibility

Document

Title

  • Brief Title: Study of Lorlatinib In Participants With Anaplastic Lymphoma Kinase (ALK) -Positive NSCLC
  • Official Title: Single-Arm Study of Lorlatinib in Participants With Anaplastic Lymphoma Kinase (ALK)-Positive Non-Small Cell Lung Cancer (NSCLC) Whose Disease Progressed After One Prior Second-Generation ALK Tyrosine Kinase Inhibitor (TKI)

Clinical Trial IDs

  • ORG STUDY ID: B7461027
  • SECONDARY ID: 2019-002504-41
  • NCT ID: NCT04362072

Conditions

  • Carcinoma
  • Non-Small-Cell Lung

Interventions

DrugSynonymsArms
LorlatinibLorlatinib

Purpose

A Phase 4 study to assess Overall and Intracranial Response Rate of single-agent lorlatinib in participants with advanced ALK-positive NSCLC whose disease has progressed on alectinib or ceritinib as the first ALK tyrosine kinase inhibitor (TKI)therapy.

Trial Arms

NameTypeDescriptionInterventions
LorlatinibExperimentalParticipants will take 100 mg (four, 25 mg tablets) once daily.
  • Lorlatinib

Eligibility Criteria

        Inclusion Criteria:

          -  Participants must have evidence of histologically or cytologically confirmed diagnosis
             of metastatic NSCLC (Stage IV, American Joint Committee on Cancer [AJCC] v7.0) that
             carries an ALK rearrangement, as determined by the Food and Drug Administration (FDA)
             approved fluorescence in situ hybridization (FISH) assay (Abbott Molecular Inc) or by
             Immunohistochemistry (IHC) (Ventana Inc).

          -  Disease Status Requirements: disease progression after alectinib or ceritinib as first
             line therapy (the study will limit enrollment of participants with best response of
             progression or indeterminate on prior alectinib to 8 participants). Participants may
             have had prior chemotherapy, but only if before starting treatment with alectinib or
             ceritinib.

          -  Tumor Requirements: All Participants must have at least one measurable target
             extracranial lesion according to RECIST v1.1. Participants with asymptomatic CNS
             metastases (including participants controlled with stable or decreasing steroid use
             within the last 2 weeks prior to study entry) will be eligible. Participants who have
             leptomeningeal disease (LM) or carcinomatous meningitis (CM) will be eligible if the
             LM/CM is visualized on magnetic resonance imaging (MRI) or if documented baseline
             cerebral spinal fluid (CSF) positive cytology is available.

          -  Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0 or 1.

          -  Adequate bone marrow functioning, pancreatic function, renal function and liver
             function

          -  Acute effects of any prior therapy resolved to baseline severity or to CTCAE Grade ≤1
             except for adverse events (AEs) that in the investigator' judgment do not constitute a
             safety risk for the participant.

          -  Systemic anti-cancer therapy with alectinib or ceritinib discontinued within a minimum
             of 5 half-lives prior to first dose of lorlatinib on the study (unless clinically
             meaningful tumor flare per discretion of the investigator, in which discussion with
             the sponsor is warranted).

          -  Male participants are eligible to participate if they agree to use proper
             contraception during the intervention period and for at least 98 days after the last
             dose of study intervention

          -  Female participants are eligible to participate if they are not pregnant or
             breastfeeding, and agree to use proper contraception during the intervention period
             and for at least 35 days after the last dose of study intervention.

          -  Capable of giving signed informed consent and willingness and ability to comply with
             the study scheduled visits and other procedures.

        Exclusion criteria:

          -  Prior ALK TKI treatment or anti-cancer treatment other than first line alectinib or
             ceritinib.

          -  Spinal cord compression unless the participant has good pain control attained through
             therapy, and there is stabilization or recovery of neurological function for the 4
             weeks prior to randomization.

          -  Gastrointestinal abnormalities, including inability to take oral medication;
             requirement for intravenous alimentation; prior surgical procedures affecting
             absorption including total gastric resection or lap band; active inflammatory
             gastrointestinal disease, chronic diarrhea, symptomatic diverticular disease;
             treatment for active peptic ulcer disease in the past 6 months; malabsorption
             syndromes.

          -  Active and clinically significant bacterial, fungal, or viral infection including
             hepatitis B virus (HBV) or hepatitis C virus (HCV), known human immunodeficiency virus
             (HIV), or acquired immunodeficiency syndrome (AIDS) related illness.

          -  Clinically significant vascular (both arterial and venous) and non-vascular cardiac
             conditions, (active or within 3 months prior to enrollment)

          -  Participants presenting with abnormal Left Ventricular Ejection Fraction (LVEF) by
             echocardiogram or Multi-Gated Acquisition Scan according to institutional lower
             limits.

          -  Participants with predisposing characteristics for acute pancreatitis according to
             investigator judgment

          -  History or known presence of interstitial fibrosis, interstitial lung disease,
             pneumonitis, hypersensitivity pneumonitis, interstitial pneumonia, obliterative
             bronchiolitis, and pulmonary fibrosis.

          -  Other severe acute or chronic medical or psychiatric condition, including recent
             (within the past year) or active suicidal ideation or behavior, or laboratory
             abnormality that may increase the risk associated with study participation or
             investigational product administration or may interfere with the interpretation of
             study results and, in the judgment of the investigator, would make the participant
             inappropriate for entry into this study.

          -  Evidence of active malignancy (other than current NSCLC, non-melanoma skin cancer, in
             situ cervical cancer, papillary thyroid cancer, ductal carcinoma in situ (DCIS) of the
             breast or localized and presumed cured prostate cancer) within the last 3 years prior
             to randomization.

          -  Radiation therapy (except palliative to relieve bone pain) within 2 weeks of study
             entry. Palliative radiation must have been completed at least 48 hours prior to study
             entry. Stereotactic or small field brain irradiation must have completed at least 2
             weeks prior to study entry. Whole brain radiation must have completed at least 4 weeks
             prior to study entry.

          -  Prior irradiation to >25% of the bone marrow.

          -  Concurrent use of any of the following food or drugs within 12 days prior to the first
             dose of lorlatinib: known strong CYP3A inducers, known strong CYP3A inhibitors, known
             CYP3A substrates with narrow therapeutic index, known permeability glycoprotein (P-gp)
             substrates with a narrow therapeutic index

          -  Major surgery within 4 weeks prior to enrollment.

          -  Known prior or suspected severe hypersensitivity to study interventions or any
             component in their formulations.

          -  Investigator site staff members directly involved in the conduct of the study and
             their family members, site staff members otherwise supervised by the investigator, or
             Pfizer employees, including their family members, directly involved in the conduct of
             the study.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Percentage of Patients With Overall Objective Response (OR) based on independent central review (ICR)
Time Frame:every 6 weeks up to 3.5 years
Safety Issue:
Description:OR (Objective Response) based on ICR assessment is defined as complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Both CR and PR must be confirmed by repeat assessments performed no less than 4 weeks after the criteria for response are first met.

Secondary Outcome Measures

Measure:Percentage of Patients With Overall OR based on Investigator (INV)
Time Frame:every 6 weeks up to 3.5 years
Safety Issue:
Description:OR based on INV assessment is defined as CR or PR according to RECIST v1.1. Both CR and PR must be confirmed by repeat assessments performed no less than 4 weeks after the criteria for response are first met.
Measure:Percentage of Patients With Intra-Cranial Objective Response (IC-OR) based on ICR/derived INV
Time Frame:every 6 weeks up to 3.5 years
Safety Issue:
Description:IC-OR is defined as Intra-Cranial complete response (IC-CR) or partial response (IC-PR) according to RECIST v1.1. Both IC-CR and IC-PR must be confirmed by repeat assessments performed no less than 4 weeks after the criteria for response are first met.
Measure:Time to Response (TTR) based on ICR/derived INV
Time Frame:every 6 weeks up to 3.5 years
Safety Issue:
Description:TTR is defined, for participants with a confirmed OR, as the time from the date of first dose to the first documentation of objective response (CR or PR) which is subsequently confirmed.
Measure:Time to Intra-Cranial Response (IC-TTR) based on ICR/derived investigator
Time Frame:every 6 weeks up to 3.5 years
Safety Issue:
Description:IC-TTR is defined, for participants with a confirmed intra-cranial objective response, as the time from the date of first dose to the first documentation of objective intra-cranial response (CR or PR) which is subsequently confirmed.
Measure:Duration of Response (DoR) based on ICR/ derived investigator
Time Frame:every 6 weeks up to 3.5 years
Safety Issue:
Description:DoR is defined, for participants with a confirmed objective response, as the time from first documentation of objective response (CR or PR whichever is earlier) to the date of first documentation of PD or death due to any cause, whichever occurs first
Measure:Duration of Intra-Cranial Response (IC-DoR) based on ICR/ derived INV
Time Frame:every 6 weeks up to 3.5 years
Safety Issue:
Description:IC-DoR is defined, for participants with a confirmed objective intra-cranial response, as the time from first documentation of objective intra-cranial response (CR or PR whichever is earlier) to the date of first documentation of PD in brain or death due to any cause, whichever occurs first.
Measure:Progression Free Survival (PFS) based on ICR/derived INV
Time Frame:every 6 weeks up to 3.5 years
Safety Issue:
Description:PFS is defined as the time from date of first dose to the date of the first documentation of PD (per RECIST v1.1) or death due to any cause, whichever occurs first.
Measure:Time To Progression (TTP) based on ICR/derived INV
Time Frame:every 6 weeks up to 3.5 years
Safety Issue:
Description:TTP is defined as the time from date of first dose to the date of the first documentation of PD (per RECIST v1.1).
Measure:Adverse Event (AE) as graded by NCI CTCAE (v 4.03)
Time Frame:From study start up to 3.5 years
Safety Issue:
Description:Frequency of patients experiencing treatment-emergent AEs (TEAEs)

Details

Phase:Phase 4
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Pfizer

Last Updated

August 10, 2020