Hepatic Impairment Study for Lorlatinib in Cancer Patients

NCT03726333 | Terminated Phase 1 Results FDA Drug

• 3 other identifiers: B7461009lorlatinib HEPATIC IMPAIRMENTHEPATIC IMPAIRMENT
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 10

Brief Summary

This is a phase 1 study in advanced cancer patients with varied hepatic functions to evaluate the potential effect of hepatic impairment on pharmacokinetics and safety of lorlatinib and provide dose recommendation for patients with hepatic impairment if possible.

Conditions

Advanced Cancers

Keywords

hepatic impairment; lorlatinib; cancer; pharmacokinetic; Lung cancer

Outcome Measures

Primary Outcomes (2)

• Area Under Plasma Lorlatinib Concentration-Time Curve From Time 0 to Dosing Interval of 24 Hours (AUC24) at Steady State On Cycle 2 Day 1

  AUC24 was defined as area under the plasma concentration time profile during 1 dosing interval (24 hours).

  Cycle 2 day 1 at times 0 (predose), 0.5, 1, 2, 4, 6, 10, and 24 hours post lorlatinib dose.

• Observed Maximal Plasma Concentration (Cmax) at Steady State on Cycle 2 Day 1

  Cmax was defined as maximum plasma concentration and was observed directly from data.

  Cycle 2 day 1 at times 0 (predose), 0.5, 1, 2, 4, 6, 10, and 24 hours post lorlatinib dose.

Secondary Outcomes (21)

• Number Of Patients Experienced Treatment Emergent Adverse Event Assessed by Investigator

  From Screening (within 28 days prior to Cycle 1 Day 1) through and including at least 28 days after after the last lorlatinib dose. The duration is approximately 42 days.

• Objective Response Rate (ORR)

  Baseline up to approximately 1 year

• Duration of Response (DR)

  Baseline up to approximately 1 year

• Lorlatinib Area Under Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) After Single Dose on Cycle 1 Day 1

  Cycle 1 day 1 at times 0 (predose), 0.5, 1, 2, 4, 6, 10, and 24 hours post lorlatinib dose.

• The Time of The Last Quantifiable Concentration (Tlast) of Lorlatinib After Single Dose on Cycle 1 Day 1

  Cycle 1 day 1 at times 0 (predose), 0.5, 1, 2, 4, 6, 10, and 24 hours post lorlatinib dose.

Study Arms (5)

Group A1 Normal hepatic function

ACTIVE COMPARATOR

continued daily administration of lorlatinib in patients with normal hepatic function

Drug: lorlatinib

Group A2 Normal hepatic function

ACTIVE COMPARATOR

continued daily administration of lorlatinib in patients with normal hepatic function

Drug: lorlatinib

Group B mild hepatic impairment

EXPERIMENTAL

continued daily administration of lorlatinib in patients with mild hepatic impairment

Drug: lorlatinib

Group C moderate hepatic impairment

EXPERIMENTAL

continued daily administration of lorlatinib in patients with moderate hepatic impairment

Drug: lorlatinib

Group D severe hepatic impairment

EXPERIMENTAL

continued daily administration of lorlatinib in patients with severe hepatic impairment

Drug: lorlatinib

Interventions

lorlatinib DRUG

continued daily administration of 100 mg lorlatinib

Group A1 Normal hepatic function

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically or cytologically confirmed solid malignancy or lymphoma that is metastatic or unresectable, and for which standard curative or palliative measures do not exist, or are no longer effective;
• Biliary obstruction with a biliary drain or stent;
• Neurologically stable gliomas and brain metastases;
• ECOG performance status of 0, 1, or 2;
• adequate bone marrow function;
• adequate pancreatic function;
• adequate renal function;
• female patients with negative pregnancy test

You may not qualify if:

• untreated esophageal varices; uncontrolled ascites;
• episodes of hepatic encephalopathy within the last 4 weeks;
• spinal cord compression; major surgery within 4 weeks prior to enrollment;
• radiation therapy within 2 weeks prior to enrollment;
• last anti-cancer treatment within 2 weeks prior to screening;
• previous high-dose chemotherapy requiring stem cell rescue;
• prior to irradiation to \>25% of the bone marrow;
• gastrointestinal abnormalities;
• known prior or suspected hypersensitivity to lorlatinib or lorlatinib tablet;
• clinically significant bacterial, fungal or viral infections for non-liver cancer patients;
• clinically significant cardiovascular disease;
• uncontrolled hypertension; acute pancreatitis with predisposing characteristics;
• history of grade 3 or 4 interstitial fibrosis or interstitial lung disease;
• active hemoelysis or evidence of biliary sepsis;
• prior major gastrointestinal surgery;

Sponsors & Collaborators

• Pfizer: lead

Study Sites (10)

University of Colorado Denver CTO (CTRC)

Aurora, Colorado, 80045, United States

Location

University of Colorado Hospital, Anschutz Cancer Pavilion (ACP)

Aurora, Colorado, 80045, United States

Location

University of Colorado Hospital, Anschutz Inpatient Pavilion (AIP)

Aurora, Colorado, 80045, United States

Location

University of Colorado Hospital, Anschutz Outpatient Pavilion (AOP)

Aurora, Colorado, 80045, United States

Location

Emory University Hospital

Atlanta, Georgia, 30322, United States

Location

Investigational Drug Service

Atlanta, Georgia, 30322, United States

Location

The Emory Clinic

Atlanta, Georgia, 30322, United States

Location

Winship Cancer Institute, Emory University

Atlanta, Georgia, 30322, United States

Location

Mays Cancer Center

San Antonio, Texas, 78229, United States

Location

University Health System

San Antonio, Texas, 78229, United States

Location

Related Links

• To obtain contact information for a study center near you, click here.

MeSH Terms

Conditions

Neoplasms; Lung Neoplasms

Interventions

lorlatinib

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Lung Diseases; Respiratory Tract Diseases

Limitations and Caveats

The study was terminated due to difficulties with enrolling eligible patients. Only 1 participant was enrolled in this study. Outcome measures and AE data were not reported as planned in the protocol because doing so would risk re-dentification of the individual participant.

Results Point of Contact

• Title: Pfizer ClinicalTrials.gov Call Center
• Organization: Pfizer Inc.

ClinicalTrials_gov_Inquiries@pfizer.com

1-800-718-1021

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Patients in the study will be assigned to different groups according to their liver function. Patients in each group will receive specific lorlatinib dose. Plasma samples for pharmacokinetic analysis will be collected in all patients. Safety and efficacy will also be followed in all patients until at least 28 days after the last study treatment.

Study Record Dates

• First Submitted: September 24, 2018
• First Posted: October 31, 2018
• Study Start: January 14, 2020
• Primary Completion: July 8, 2021
• Study Completion: July 8, 2021
• Last Updated: June 21, 2024
• Results First Posted: June 21, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (10)