Study of Lorlatinib In People With ALK-positive Non-small Cell Lung Cancer
- Registration Number
- NCT04362072
- Lead Sponsor
- Pfizer
- Brief 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 71
- 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.
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Lorlatinib Lorlatinib Participants will take 100 mg (four, 25 mg tablets) once daily.
- Primary Outcome Measures
Name Time Method Percentage of Patients With Overall Objective Response (OR) based on independent central review (ICR) every 6 weeks up to approximately 4 years 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
Name Time Method Percentage of Patients With Intra-Cranial Objective Response (IC-OR) based on ICR/derived INV every 6 weeks up to approximately 4 years 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.
Time to Response (TTR) based on ICR/derived INV every 6 weeks up to approximately 4 years 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.
Percentage of Patients With Overall OR based on Investigator (INV) every 6 weeks up to approximately 4 years 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.
Duration of Response (DoR) based on ICR/ derived investigator every 6 weeks up to approximately 4 years 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
Duration of Intra-Cranial Response (IC-DoR) based on ICR/ derived INV every 6 weeks up to approximately 4 years 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.
Adverse Event (AE) as graded by NCI CTCAE (v 4.03) From study start up to approximately 4 years Frequency of patients experiencing treatment-emergent AEs (TEAEs)
Time to Intra-Cranial Response (IC-TTR) based on ICR/derived investigator every 6 weeks up to approximately 4 years 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.
Time To Progression (TTP) based on ICR/derived INV every 6 weeks up to approximately 4 years TTP is defined as the time from date of first dose to the date of the first documentation of PD (per RECIST v1.1).
Progression Free Survival (PFS) based on ICR/derived INV every 6 weeks up to approximately 4 years 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.
Trial Locations
- Locations (41)
Policlinico "G. Rodolico"
🇮🇹Catania, Italy
UCI Medical Center/Chao Family Comprehensive Cancer Center
🇺🇸Orange, California, United States
University Cancer & Blood Center, Llc
🇺🇸Athens, Georgia, United States
Medanta-The Medicity
🇮🇳Gurgaon, Haryana, India
Fondazione IRCCS San Gerardo dei Tintori
🇮🇹Monza, Lombardia, Italy
Bhakti Vedanta Hospital and Research Institute
🇮🇳Thane, Maharashtra, India
Ospedale San Gerardo ASST Monza Oncologia Medica
🇮🇹Monza, Monza AND Brianza, Italy
Azienda Ospedaliera Dei Colli
🇮🇹Naples, Napoli, Italy
Azienda Ospedaliero Universitaria di Parma
🇮🇹Parma, PR, Italy
A.O. Ospedali Riuniti Marche Nord - Presidio San Salvatore - Muraglia
🇮🇹Pesaro, PU, Italy
Istituto di Candiolo IRCCS - Fondazione del Piemonte per l'Oncologia
🇮🇹Candiolo, Torino, Italy
Azienda Ospedaliera San Camillo Forlanini
🇮🇹Roma, Rome, Italy
AOU San Luigi Gonzaga
🇮🇹Orbassano (TO), TO, Italy
AO Santa Maria della Misericordia
🇮🇹Perugia, Umbria, Italy
Azienda Ospedaliera San Giuseppe Moscati
🇮🇹Avellino, Italy
Ms Pneumed Janusz Milanowski, Katarzyna Szmygin-Milanowska Spolka Jawna
🇵🇱Lublin, Poland
Centrum Medyczne Luxmed Sp. z o.o.
🇵🇱Lublin, Poland
Elkardia Lubelskie Centrum Kardiologii
🇵🇱Lublin, Poland
Centrum Medyczne EVOMED
🇵🇱Szczecin, Poland
Dom Lekarski Centrum Medyczne Outlet Park
🇵🇱Szczecin, Poland
Samodzielny Publiczny Szpital Kliniczny Nr 1 im. prof. Tadeusza Sokolowskiego Pomorskiego UM
🇵🇱Szczecin, Poland
Pracownia Medycyny Nuklearnej, 109 Szpital Wojskowy z Przychodnia SP ZOZ
🇵🇱Szczecin, Poland
Hospital Universitario Puerta de Hierro Majadahonda
🇪🇸Majadahonda, Madrid, Spain
Hospital Teresa Herrera (C.H.U.A.C)
🇪🇸A Coruña, 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 Virgen del Rocio
🇪🇸Sevilla, Spain
Hospital Regional Universitario de Malaga
🇪🇸Malaga, Spain
Hospital Universitari i Politecnic La Fe
🇪🇸Valencia, Spain
NIHR/Wellcome Trust Clinical Research Facility
🇬🇧Manchester, United Kingdom
IRCCS Ospedale San Raffaele
🇮🇹Milano, MI, Italy
Azienda Sanitaria Territoriale (AST) Pesaro Urbino
🇮🇹Pesaro, Pesaro AND Urbino, Italy
Centro Riferimento Oncologico di Aviano - IRCCS SOC Oncologia Medica e dei Tumori Immunocorrelati
🇮🇹Aviano, PN, Italy
The Christie NHS Foundation Trust
🇬🇧Manchester, United Kingdom
Kantonsspital Graubuenden
🇨🇭Chur, Graubuenden, Switzerland
Rajiv Gandhi Cancer Institute And Research Centre
🇮🇳New Delhi, DEL, India
Dom Lekarski S.A.
🇵🇱Szczecin, Poland
Healthcare Global Enterprises
🇮🇳Bengaluru, Karnataka, India
Guy's and St Thomas' NHS Foundation Trust
🇬🇧London, United Kingdom