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Trial record 1 of 1 for:    NCT03726333
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Hepatic Impairment Study for Lorlatinib in Cancer Patients

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ClinicalTrials.gov Identifier: NCT03726333
Recruitment Status : Recruiting
First Posted : October 31, 2018
Last Update Posted : June 20, 2019
Sponsor:
Information provided by (Responsible Party):
Pfizer

Tracking Information
First Submitted Date  ICMJE September 24, 2018
First Posted Date  ICMJE October 31, 2018
Last Update Posted Date June 20, 2019
Estimated Study Start Date  ICMJE June 11, 2019
Estimated Primary Completion Date January 25, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 29, 2018)
  • Plasma lorlatinib AUC24 at steady state [ Time Frame: cycle 2 day 1 up to 24 hours post lorlatinib dose (each cycle is 21 days) ]
    area under plasma concentration-time curve from time 0 to dosing interval of 24 hours (AUC24) at steady state on cycle 2 day 1
  • Plasma lorlatinib Cmax at steady state [ Time Frame: cycle 2 day 1 up to 24 hours post lorlatinib dose (each cycle is 21 days) ]
    observed maximal plasma concentration at steady state on cycle 2 day 1
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03726333 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: October 29, 2018)
  • Plasma lorlatinib AUClast after single dose [ Time Frame: cycle 1 day 1 up to 24 hours post lorlatinib dose (each cycle is 21 days) ]
    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.
  • Plasma lorlatinib Tlast after single dose [ Time Frame: cycle 1 day 1 up to 24 hours post lorlatinib dose (each cycle is 21 days) ]
    the time of the last quantifiable concentration (Tlast) after single dose on cycle 1 day 1.
  • Plasma lorlatinib Tmax after single dose [ Time Frame: cycle 1 day 1 up to 24 hours post lorlatinib dose (each cycle is 21 days) ]
    the time to Cmax after single dose on cycle 1 day 1.
  • Plasma lorlatinib Cmin at steady state [ Time Frame: cycle 2 day 1 up to 24 hours post lorlatinib dose (each cycle is 21 days) ]
    observed minimal plasma concentration at steady state on cycle 2 day 1.
  • Plasma lorlatinib AUClast at steady state [ Time Frame: cycle 2 day 1 up to 24 hours post lorlatinib dose (each cycle is 21 days) ]
    area under plasma concentration-time curve from time 0 to the time of the last quantifiable concentration (AUClast) at steady state on cycle 2 day 1.
  • Plasma lorlatinib Tlast at steady state [ Time Frame: cycle 2 day 1 up to 24 hours post lorlatinib dose (each cycle is 21 days) ]
    the time of the last quantifiable concentration (Tlast) at steady state on cycle 2 day 1.
  • lorlatinib CL/F at steadys state [ Time Frame: cycle 2 day 1 up to 24 hours post lorlatinib dose (each cycle is 21 days) ]
    lorlatinib apparent clearance at steady state on cycle 2 day 1
  • plasma lorlatinib metabolite AUC24 at steady state [ Time Frame: cycle 2 day 1 up to 24 hours post lorlatinib dose (each cycle is 21 days) ]
    area under plasma concentration-time curve from time 0 to dosing interval of 24 hours (AUC24) at steady state on cycle 2 day 1
  • Plasma lorlatinib metabolite AUClast after single dose [ Time Frame: cycle 1 day 1 up to 24 hours post lorlatinib dose (each cycle is 21 days) ]
    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.
  • Plasma lorlatinib metabolite AUClast at steady state [ Time Frame: cycle 2 day 1 up to 24 hours post lorlatinib dose (each cycle is 21 days) ]
    area under plasma concentration-time curve from time 0 to the time of the last quantifiable concentration (AUClast) at steady state on cycle 2 day 1.
  • Plasma lorlatinib metabolite Cmax at steady state [ Time Frame: cycle 2 day 1 up to 24 hours post lorlatinib dose (each cycle is 21 days) ]
    observed maximal plasma concentration at steady state on cycle 2 day 1.
  • Plasma lorlatinib metabolite Cmax after single dose [ Time Frame: cycle 1 day 1 up to 24 hours post lorlatinib dose (each cycle is 21 days) ]
    observed maximal plasma concentration after single dose on cycle 1 day 1.
  • Plasma lorlatinib metabolite Tmax after single dose [ Time Frame: cycle 1 day 1 up to 24 hours post lorlatinib dose (each cycle is 21 days) ]
    the time to Cmax after single dose on cycle 1 day 1.
  • Plasma lorlatinib metabolite Tmax at steady state [ Time Frame: cycle 2 day 1 up to 24 hours post lorlatinib dose (each cycle is 21 days) ]
    the time to Cmax at steady state on cycle 2 day 1.
  • Plasma lorlatinib metabolite Tlast after single dose [ Time Frame: cycle 1 day 1 up to 24 hours post lorlatinib dose (each cycle is 21 days) ]
    the time of the last quantifiable concentration (Tlast) after single dose on cycle 1 day 1.
  • Plasma lorlatinib metabolite Tlast at steady state [ Time Frame: cycle 2 day 1 up to 24 hours post lorlatinib dose (each cycle is 21 days) ]
    the time of the last quantifiable concentration (Tlast) at steady state on cycle 2 day 1.
  • MRAUC24 at steady state [ Time Frame: cycle 2 day 1 up to 24 hours post lorlatinib dose (each cycle is 21 days) ]
    metabolite ratio of lorlatinib metabolite for AUC24 at steady state on cycle 2 day 1
  • MRAUClast at steady state [ Time Frame: cycle 2 day 1 up to 24 hours post lorlatinib dose (each cycle is 21 days) ]
    metabolite ratio of lorlatinib metabolite for AUClast at steady state on cycle 2 day 1
  • MRCmax at steady state [ Time Frame: cycle 2 day 1 up to 24 hours post lorlatinib dose (each cycle is 21 days) ]
    metabolite ratio of lorlatinib metabolite for Cmax at steady state on cycle 2 day 1
  • MRAUClast after single dose [ Time Frame: cycle 2 day 1 up to 24 hours post lorlatinib dose (each cycle is 21 days) ]
    metabolite ratio of lorlatinib metabolite for AUClast after single dose on cycle 1 day 1
  • number of patients experienced treatment emergent adverse event assessed by investigator [ Time Frame: until at least 28 days after the last lorlatinib dose ]
    Type, incidence, severity, seriousness, and relationship to study medications of adverse events (AE) and any laboratory abnormalities
  • ORR [ Time Frame: baseline up to approximately 1 year ]
    objective response rate (ORR) is defined as the percent of patients with complete response (CR) or partial response (PR) based on investigator evaluation, according to RECIST v1.1 relative to the response-evaluable population
  • DR [ Time Frame: baseline up to approximately 1 year ]
    Duration of response (DR) will be measured from the date that an objective tumor response (CR or PR) is first documented (whichever occurs first) to date of objective tumor progression or death due to any cause, whichever occurs first
  • number of patients experienced treatment related adverse event assessed by investigator [ Time Frame: until at least 28 days after the last lorlatinib dose ]
    Type, incidence, severity, seriousness, and relationship to study medications of adverse events (AE) and any laboratory abnormalities
  • number of patients experienced treatment emergent serious adverse event assessed by investigator [ Time Frame: until at least 28 days after the last lorlatinib dose ]
    Type, incidence, severity, seriousness, and relationship to study medications of adverse events (AE) and any laboratory abnormalities
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Hepatic Impairment Study for Lorlatinib in Cancer Patients
Official Title  ICMJE A PHASE 1 STUDY TO EVALUATE THE EFFECT OF HEPATIC IMPAIRMENT ON THE PHARMACOKINETICS AND SAFETY OF LORLATINIB IN ADVANCED CANCER PATIENTS
Brief Summary This is a phase 1 study in advanced cancer patients with varied hepatic fucntions 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.
Detailed Description

This will be a Phase 1, open label, multi center, multiple dose, non randomized, Phase 1 clinical trial of lorlatinib in advanced cancer patients with varying degrees of hepatic impairment and necessary age , weight , and gender matched prospect normal hepatic function patients. This study is intended to evaluate the potential effect of hepatic impairments on the PK and safety of lorlatinib after daily administration of lorlatinib and to provide dosing recommendation for patients with varied degree of hepatic impairment if possible.

Patients in the study will be assigned to different groups (A1, normal liver function, control for group B; A2, normal liver function, control for group C; B, mild hepatic impairment; C, moderate hepatic impairment; D, severe hepatic impairment) according to their liver function. The enrollment of approximately 76 advanced cancer patients is anticipated in this study in order to have 8 PK-evaluable patients in each of Groups A1, A2, B and C, and 6 PK-evaluable patients in Group D for final statistical analysis. Evaluable patients are those who complete the planned PK sample collection on Cycle 2 Day 1 and have no lorlatinib dose modification until completion of Cycle 2 Day 1 PK evaluation. Patients who are not evaluable for PK will be replaced. Each patient will be treated with repeated oral once daily doses of lorlatinib in 21-day cycles until disease progression, patient refusal, or unacceptable toxicity occurs. The dose schedule may be modified as necessary for individual patients according to tolerability.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
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.
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Advanced Cancers
Intervention  ICMJE
  • Drug: lorlatinib
    continued daily administration of 100 mg lorlatinib
  • Drug: lorlatinib
    continued daily administration of lorlatinib at the dose level same as Group C for the first 22 days and 100 mg QD afterwards
  • Drug: lorlatinib
    continued daily administration of 100 mg QD lorlatinib
  • Drug: lorlatinib
    continued daily administration of lorlatinib at 50 mg QD initially and may be adjusted based on PK and safety results from the initial several patients
  • Drug: lorlatinib
    continued daily administration of lorlatinib at the dose level determined based on preliminary PK and safety results from first several patients in Group C
Study Arms  ICMJE
  • Active Comparator: Group A1 Normal hepatic function
    continued daily administration of lorlatinib in patients with normal hepatic function
    Intervention: Drug: lorlatinib
  • Active Comparator: Group A2 Normal hepatic function
    continued daily administration of lorlatinib in patients with normal hepatic function
    Intervention: Drug: lorlatinib
  • Experimental: Group B mild hepatic impairment
    continued daily administration of lorlatinib in patients with mild hepatic imapirment
    Intervention: Drug: lorlatinib
  • Experimental: Group C moderate hepatic impairment
    continued daily administration of lorlatinib in patients with moderate hepatic impairment
    Intervention: Drug: lorlatinib
  • Experimental: Group D severe hepatic impairment
    continued daily administration of lorlatinib in patients with severe hepatic impairment
    Intervention: Drug: lorlatinib
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: October 29, 2018)
76
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE July 6, 2022
Estimated Primary Completion Date January 25, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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;
  • concurrent use of known strong CYP3A inhibitors, inducers and P-gp substrates with a narrow therapeutic index;
  • concurrent use of CYP3A substrates with narrow therapeutic indices;
  • prior treatment with lorlatinib; active bleeding disorder
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Pfizer CT.gov Call Center 1-800-718-1021 ClinicalTrials.gov_Inquiries@pfizer.com
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03726333
Other Study ID Numbers  ICMJE B7461009
lorlatinib HEPATIC IMPAIRMENT ( Other Identifier: Alias Study Number )
HEPATIC IMPAIRMENT ( Other Identifier: Alias Study Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.
Responsible Party Pfizer
Study Sponsor  ICMJE Pfizer
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Pfizer CT.gov Call Center Pfizer
PRS Account Pfizer
Verification Date June 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP