Study of Lorlatinib In People With ALK-positive Non-small Cell Lung Cancer

Carcinoma Clinical Trial

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 Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04362072
• Other study ID #: B7461027
• Secondary ID: 2019-002504-41
• Status: Active, not recruiting
• Phase: Phase 4
• Start date: September 29, 2020
• Est. completion date: June 25, 2024

Study information

• Verified date: March 2024
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this clinical trial is to learn whether the study medicine (called lorlatinib) is safe and effective for the treatment of non-small cell lung cancer that is caused by an abnormal anaplastic lymphoma kinase (ALK) gene.

This study is seeking participants whose lung cancer has progressed after receiving either alectinib or ceritinib as their first treatment.

Participants will take part in this study for up to approximately 4 years, depending on when the study is completed and how their cancer responds to the study treatment. They will take lorlatinib orally (by mouth) once daily.

Participants will visit the study site about every six weeks to meet with the study team. During these visits, the study team will monitor the safety and effects of lorlatinib.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 71
• Est. completion date: June 25, 2024
• Est. primary completion date: June 25, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

• 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.

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Non-Small-Cell Lung
• Non-Small-Cell Lung

Intervention

Drug:
• Lorlatinib
25 milligram (mg) tablet

Locations

Country	Name	City	State
India	Healthcare Global Enterprises	Bengaluru	Karnataka
India	Medanta-The Medicity	Gurgaon	Haryana
India	Rajiv Gandhi Cancer Institute And Research Centre	New Delhi	Delhi
India	Rajiv Gandhi Cancer Institute And Research Centre	New Delhi	DEL
India	Bhakti Vedanta Hospital and Research Institute	Thane	Maharashtra
Italy	Azienda Ospedaliera San Giuseppe Moscati	Avellino
Italy	Centro Riferimento Oncologico di Aviano - IRCCS SOC Oncologia Medica e dei Tumori Immunocorrelati	Aviano	PN
Italy	Istituto di Candiolo IRCCS - Fondazione del Piemonte per l'Oncologia	Candiolo	Torino
Italy	Policlinico "G. Rodolico"	Catania
Italy	IRCCS Ospedale San Raffaele	Milano	MI
Italy	Fondazione IRCCS San Gerardo dei Tintori	Monza	Lombardia
Italy	Ospedale San Gerardo ASST Monza Oncologia Medica	Monza	Monza AND Brianza
Italy	Azienda Ospedaliera Dei Colli	Naples	Napoli
Italy	AOU San Luigi Gonzaga	Orbassano (TO)	TO
Italy	Azienda Ospedaliero Universitaria di Parma	Parma	PR
Italy	AO Santa Maria della Misericordia	Perugia	Umbria
Italy	A.O. Ospedali Riuniti Marche Nord - Presidio San Salvatore - Muraglia	Pesaro	PU
Italy	Azienda Sanitaria Territoriale (AST) Pesaro Urbino	Pesaro	Pesaro AND Urbino
Italy	Azienda Ospedaliera San Camillo Forlanini	Roma	Rome
Poland	Centrum Medyczne Luxmed Sp. z o.o.	Lublin
Poland	Elkardia Lubelskie Centrum Kardiologii	Lublin
Poland	Ms Pneumed Janusz Milanowski, Katarzyna Szmygin-Milanowska Spolka Jawna	Lublin
Poland	Centrum Medyczne EVOMED	Szczecin
Poland	Dom Lekarski Centrum Medyczne Outlet Park	Szczecin
Poland	Dom Lekarski S.A.	Szczecin
Poland	Pracownia Medycyny Nuklearnej, 109 Szpital Wojskowy z Przychodnia SP ZOZ	Szczecin
Poland	Samodzielny Publiczny Szpital Kliniczny Nr 1 im. prof. Tadeusza Sokolowskiego Pomorskiego UM	Szczecin
Spain	Hospital Teresa Herrera (C.H.U.A.C)	A Coruña
Spain	Hospital de la Santa Creu i Sant Pau	Barcelona
Spain	Hospital de la Santa Creu i Sant Pau	Barcelona
Spain	Hospital Universitari Vall d'Hebron	Barcelona
Spain	ICO L'Hospitalet (Hospital Duran i Reynals)	L'Hospitalet de Llobregat
Spain	Hospital Universitario Ramon y Cajal	Madrid
Spain	Hospital Universitario Puerta de Hierro Majadahonda	Majadahonda	Madrid
Spain	Hospital Regional Universitario de Malaga	Malaga
Spain	Hospital Universitario Virgen del Rocio	Sevilla
Spain	Hospital Universitari i Politecnic La Fe	Valencia
Switzerland	Kantonsspital Graubuenden	Chur	Graubuenden
United Kingdom	Guy's and St Thomas' NHS Foundation Trust	London
United Kingdom	NIHR/Wellcome Trust Clinical Research Facility	Manchester
United Kingdom	The Christie NHS Foundation Trust	Manchester
United States	University Cancer & Blood Center, Llc	Athens	Georgia
United States	UCI Medical Center/Chao Family Comprehensive Cancer Center	Orange	California

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Countries where clinical trial is conducted

United States,  India,  Italy,  Poland,  Spain,  Switzerland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Patients With Overall Objective Response (OR) based on independent central review (ICR)	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.	every 6 weeks up to approximately 4 years
Secondary	Percentage of Patients With Overall OR based on Investigator (INV)	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.	every 6 weeks up to approximately 4 years
Secondary	Percentage of Patients With Intra-Cranial Objective Response (IC-OR) based on ICR/derived INV	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.	every 6 weeks up to approximately 4 years
Secondary	Time to Response (TTR) based on ICR/derived INV	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.	every 6 weeks up to approximately 4 years
Secondary	Time to Intra-Cranial Response (IC-TTR) based on ICR/derived investigator	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.	every 6 weeks up to approximately 4 years
Secondary	Duration of Response (DoR) based on ICR/ derived investigator	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	every 6 weeks up to approximately 4 years
Secondary	Duration of Intra-Cranial Response (IC-DoR) based on ICR/ derived INV	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.	every 6 weeks up to approximately 4 years
Secondary	Progression Free Survival (PFS) based on ICR/derived INV	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.	every 6 weeks up to approximately 4 years
Secondary	Time To Progression (TTP) based on ICR/derived INV	TTP is defined as the time from date of first dose to the date of the first documentation of PD (per RECIST v1.1).	every 6 weeks up to approximately 4 years
Secondary	Adverse Event (AE) as graded by NCI CTCAE (v 4.03)	Frequency of patients experiencing treatment-emergent AEs (TEAEs)	From study start up to approximately 4 years

External Links

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