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CTRI Number  CTRI/2023/01/049349 [Registered on: 31/01/2023] Trial Registered Prospectively
Last Modified On: 17/03/2023
Post Graduate Thesis  No 
Type of Trial  Interventional 
Type of Study   Drug 
Study Design  Single Arm Study 
Public Title of Study   Study of Lorlatinib In People With ALK-positive Non-small Cell Lung Cancer 
Scientific Title of Study   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) 
Trial Acronym   
Secondary IDs if Any  
Secondary ID  Identifier 
2019-002504-41  EudraCT 
B7461027 Final Protocol, dated 22 January 2020  Protocol Number 
NCT04362072  ClinicalTrials.gov 
 
Details of Principal Investigator or overall Trial Coordinator (multi-center study)  
Name   
Designation   
Affiliation   
Address 




 
Phone    
Fax    
Email    
 
Details of Contact Person
Scientific Query  
Name  Dr Seema Pai 
Designation  Director-Clinical Site Operations 
Affiliation  Pfizer Limited 
Address  Global Site and Study Operations, Clinical Development and Operations, Global Product Development, Pfizer Limited, The Capital, 1802/1901, Plot No. C70, G Block, Bandra Kurla Complex, Bandra(E)

Mumbai
MAHARASHTRA
400051
India 
Phone  8826422322  
Fax    
Email  seema.pai@pfizer.com  
 
Details of Contact Person
Public Query  
Name  Dr Seema Pai 
Designation  Director-Clinical Site Operations 
Affiliation  Pfizer Limited 
Address  Global Site and Study Operations, Clinical Development and Operations, Global Product Development, Pfizer Limited, The Capital, 1802/1901, Plot No. C70, G Block, Bandra Kurla Complex, Bandra(E)

Mumbai
MAHARASHTRA
400051
India 
Phone  8826422322  
Fax    
Email  seema.pai@pfizer.com  
 
Source of Monetary or Material Support  
Pfizer Inc., 235 East 42nd Street, New York, NY 10017 
 
Primary Sponsor  
Name  Pfizer Inc 
Address  235 East 42nd Street, New York, NY 10017 
Type of Sponsor  Pharmaceutical industry-Global 
 
Details of Secondary Sponsor  
Name  Address 
NIL  NIL 
 
Countries of Recruitment     India
Italy
Poland
Spain
Switzerland
United Kingdom
United States of America  
Sites of Study  
No of Sites = 4  
Name of Principal Investigator  Name of Site  Site Address  Phone/Fax/Email 
Nirmal Raut  Bhaktivedanta Hospital & Research Institute  Medical Research Department, OncologyDivision OPD 3, 1st floor,Srishti Complex, Bhaktivedanta Swami Marg, Mira Road (East) Thane 401107
Mumbai
MAHARASHTRA 		 9930398156

pinirmal123@gmail.com 
Satheesh Thungappa  Healthcare Global Enterprises Limited  Clinical Research Dept., Oncology Division, Tower 4, 5th floor, room No 8, P Kalinga Rao Road, Sampangiram nagar, 560011
Bangalore
KARNATAKA 		 9242698750

drsatheesh.ct@hcgel.com 
Ashok Vaid  Medanta -The Medicity   Clinical Research Dept., Oncology Division, 10th floor, Medical Onco and Haemato Oncology, CH Baktawar Singh Rd, Medicity, Islampur Colony,Sector-38, Gurugram-122001
Gurgaon
HARYANA 		 1244141414

Ashok.vaidmier@medanta.org 
Ullas Batra  Rajiv Gandhi Cancer Institute and Research Centre  Department of Medical Oncology, Oncology Division, Medical OPD 1st floor, D- block, Room no.3153 D-18, Sir Chotu Ram Marg, Rohini Institutional Area, Sector 5, Rohini 110085
New Delhi
DELHI 		 9711080001

ullasbatra@gmail.com 
 
Details of Ethics Committee  
No of Ethics Committees= 4  
Name of Committee  Approval Status 
Bhaktivedanta Hospital Ethics committee  Approved 
HCG Central Ethics Committee  Approved 
Institutional Review Board  Approved 
Medanta Institutional Ethics Committee  Submittted/Under Review 
 
Regulatory Clearance Status from DCGI  
Status 
Approved/Obtained 
 
Health Condition / Problems Studied  
Health Type  Condition 
Patients  (1) ICD-10 Condition: C349||Malignant neoplasm of unspecifiedpart of bronchus or lung,  
 
Intervention / Comparator Agent  
Type  Name  Details 
Intervention  Lorlatinib   Participants will take 100 mg (four, 25 mg tablets) once daily and Total duration for this drug intervention is 2 years. 
Comparator Agent  Not Applicable  Not Applicable 
 
Inclusion Criteria  
Age From  18.00 Year(s)
Age To  99.00 Year(s)
Gender  Both 
Details  1) Participants must have evidence of histologically or cytologically confirmed diagnosis of metastatic NSCLC (Stage IV, American Joint Committee on Cancer [AJCC] version 7.0) 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).

2) 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.

3) Tumor Requirements: All Participants must have at least one measurable target extracranial lesion according to RECIST version 1.1. 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.

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

5) Adequate bone marrow functioning, pancreatic function, renal function, and liver function

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

7) 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).

8) 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

9) 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.

10) Capable of giving signed informed consent and willingness and ability to comply with the study scheduled visits and other procedures.
 
 
ExclusionCriteria 
Details  1) Prior ALK TKI treatment or anti-cancer treatment other than first line alectinib or ceritinib.

2) 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.

3) 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.

4) 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.

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

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

7) Participants with predisposing characteristics for acute pancreatitis according to investigator judgment

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

9) 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.

10) 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.

11) 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.

12) Prior irradiation to >25% of the bone marrow.

13) 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

14) Major surgery within 4 weeks prior to enrollment.

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

16) 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.
 
 
Method of Generating Random Sequence   Computer generated randomization 
Method of Concealment   Centralized 
Blinding/Masking   Open Label 
Primary Outcome  
Outcome  TimePoints 
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 3.5 years 
 
Secondary Outcome  
Outcome  TimePoints 
Percentage of Patients With Overall OR based on Investigator (INV)  every 6 weeks up to 3.5 years 
Percentage of Patients With Intra-Cranial Objective Response (IC-OR) based on ICR/derived INV  every 6 weeks up to 3.5 years 
Time to Response (TTR) based on ICR/derived INV  every 6 weeks up to 3.5 years 
Time to Intra-Cranial Response (IC-TTR) based on ICR/derived investigator  every 6 weeks up to 3.5 years 
Duration of Response (DoR) based on ICR/ derived investigator  every 6 weeks up to 3.5 years 
Duration of Intra-Cranial Response (IC-DoR) based on ICR/ derived INV  every 6 weeks up to 3.5 years 
Progression Free Survival (PFS) based on ICR/derived INV  every 6 weeks up to 3.5 years 
Time To Progression (TTP) based on ICR/derived INV  every 6 weeks up to 3.5 years 
Adverse Event (AE) as graded by NCI CTCAE (v 4.03)  From study start up to 3.5 years 
 
Target Sample Size   Total Sample Size="70"
Sample Size from India="11" 
Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials"
Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials" 
Phase of Trial   Phase 4 
Date of First Enrollment (India)   01/02/2023 
Date of Study Completion (India) Applicable only for Completed/Terminated trials 
Date of First Enrollment (Global)  08/10/2020 
Date of Study Completion (Global) Applicable only for Completed/Terminated trials 
Estimated Duration of Trial   Years="3"
Months="0"
Days="0" 
Recruitment Status of Trial (Global)
Modification(s)  		 Open to Recruitment 
Recruitment Status of Trial (India)  Open to Recruitment 
Publication Details   NIL 
Individual Participant Data (IPD) Sharing Statement

Will individual participant data (IPD) be shared publicly (including data dictionaries)?  

Response - NO
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 two 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.

 
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