Lorlatinib in ALK Inhibitor Treated Unresectable Advanced/Recurrent ALK-Positive Non Small Cell Lung Cancer Patients in India

NCT04541706 | Completed Phase 4 Results

• 1 other identifier: B7461030
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 12

Brief Summary

Lorlatinib is a third-generation, oral, reversible, ATP-competitive, macrocyclic TKI of ALK and ROS1. Lorlatinib was specifically designed to penetrate the CNS and to overcome known secondary resistance mutations in the ALK tyrosine kinase domain. This is a Phase 4, open-label, multicenter, non-randomized, prospective, single arm study to evaluate the safety and tolerability of lorlatinib in adult participants with unresectable advanced and/or recurrent ALK-positive NSCLC with resistance or intolerance to at least 1 prior ALK inhibitor treatment. This study is being conducted as a post approval study to fulfill Central Drugs Standard Control Organization (CDSCO) request relating to additional information on use of Lorlatinib in Indian patients.

Conditions

Advanced Non-Small Cell Lung Cancer

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Treatment-Emergent Adverse Events (TEAEs)

  An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a product or medical device; the event did not necessarily need to have a causal relationship with the treatment or usage. A TEAE was defined as an event that emerged during treatment, having been absent pretreatment, or worsened relative to the pretreatment state. If the investigator did not know whether or not the investigational product caused the event, then the event would be handled as "related to investigational product" for reporting purposes, as defined by the sponsor. If the investigator's causality assessment was "unknown but not related to investigational product," this was clearly documented on study records.

  From Day 1 up to 35 days post last dosing date or the date of initiation of a new anticancer therapy (up to 1.9 years)

Secondary Outcomes (4)

• Confirmed Objective Responses Rate (ORR) Based on Investigator Assessment

  Assessed at least 1 year from first dose or until progression of disease, death or received subsequent anti-cancer therapy, whichever came first up to a maximum of 2 years.

• Confirmed Intracranial Objective Response Rate (IC-ORR) Based on Investigator Assessment

  Assessed at least 1 year from first dose or until progression of disease, death or received subsequent anti-cancer therapy, whichever came first up to a maximum of 2 years.

• Duration of Response (DoR)

  Assessed at least 1 year from first dose or until progression of disease, death or received subsequent anti-cancer therapy, whichever came first up to a maximum of 2 years.

• Intracranial Duration of Response (IC-DoR)

  Assessed at least 1 year from first dose or until progression of disease, death or received subsequent anti-cancer therapy, whichever came first up to a maximum of 2 years.

Study Arms (1)

Lorlatinib

EXPERIMENTAL

The recommended dosage of lorlatinib is 100 mg orally once daily, with or without food, until disease progression, unacceptable toxicity, or participant refusal/lost to follow-up. About 100 participants will be enrolled in this study.

Drug: Lorlatinib

Interventions

Lorlatinib DRUG

Lorlatinib will be supplied for oral administration as 25 mg tablets. The recommended dosage of lorlatinib is 100 mg orally once daily.

Also known as: LORBRIQUA

Lorlatinib

Eligibility Criteria

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

You may qualify if:

• Evidence of histologically or cytologically confirmed diagnosis of unresectable advanced and/or recurrent NSCLC that carries an ALK rearrangement, as detected by an appropriate test.
• Disease progression or intolerance to 1 previous treatment with ALK TKI. Participants may have also had prior chemotherapy for their advanced and/or recurrent disease.
• Participants with asymptomatic CNS metastases (including participants controlled with stable or decreasing steroid use within the last 2 weeks prior to study enrollment) will be eligible.
• Age ≥18 years.
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1, or 2.
• Adequate hematologic and renal function as defined as:
• Absolute neutrophil count (ANC) ≥1,000/mm3;
• Platelets ≥50,000/mm3;
• Hemoglobin ≥8 g/dL;
• Estimated creatinine clearance ≥30 mL/min as calculated using the method standard for the institution.
• Adequate liver function, including:
• Total serum bilirubin ≤1.5 × upper limit of normal (ULN);
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 × ULN (≤5.0 × ULN in case of liver metastases).
• Adequate pancreatic function, including:
• Serum total amylase ≤1.5 × ULN.\*

You may not qualify if:

• Radiation therapy (except palliative to relieve bone pain) within 2 weeks of study enrollment. Palliative radiation (\<10 fractions) must have been completed at least 48 hours prior to study enrollment. Stereotactic or small field brain irradiation must have completed at least 2 weeks prior to study enrollment. Whole brain radiation must have completed at least 4 weeks prior to study enrollment. Prior irradiation to \>25% of the bone marrow.
• Major surgery within 4 weeks prior to enrollment. Minor surgical procedures (eg, port insertion) are not excluded, but sufficient time should have passed for adequate wound healing.
• Known prior or suspected severe hypersensitivity to study drug or any component in its formulation.
• Active and clinically significant bacterial, fungal, or viral infection.
• Clinically significant vascular (both arterial and venous) and non-vascular cardiac conditions (active or within 3 months prior to enrollment), which may include, but are not limited to:
• Arterial disease such as cerebral vascular accident/stroke (including transient ischemic attack \[TIA\]), myocardial infarction, unstable angina;
• Venous diseases such as cerebral venous thrombosis, symptomatic pulmonary embolism;
• Non-vascular cardiac disease such as congestive heart failure (New York Heart Association Classification Class ≥II), second degree or third degree atrioventricular (AV) block (unless paced) or any AV block with PR interval \>220 msec; or ongoing cardiac dysrhythmias of NCI CTCAE Grade ≥2, uncontrolled atrial fibrillation of any grade, bradycardia defined as \<50 beats per minute (bpm) (unless participant is otherwise healthy such as long distance runners, etc.), machine read ECG with QT interval corrected for heart rate (QTc) \>470 msec, or congenital long QT syndrome.
• History or known presence of interstitial fibrosis, interstitial lung disease (ILD), 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 enrollment in 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 enrollment.
• Concurrent use of any of the following food or drugs (consult the Sponsor if in doubt whether a food or a drug falls into any of the categories described below) within 12 days prior to the first dose of lorlatinib:
• Known strong cytochrome (CYP)3A inducers (eg, carbamazepine, enzalutamide, mitotane, rifampin, St. John's Wort).
• Known strong CYP3A inhibitors (eg, grapefruit juice or grapefruit/grapefruit related citrus fruits \[eg, Seville oranges, pomelos\], boceprevir, cobicistat, clarithromycin, conivaptan, diltiazem, idelalisib, indinavir, itraconazole, ketoconazole, lopinavir, nelfinavir, paritaprevir, posaconazole, ritonavir alone and with elvitegravir or indinavir or lopinavir or paritaprevir or ombitasvir or dasabuvir or saquinavir or tipranavir, telaprevir and voriconazole). The topical use of these medications (if applicable), such as 2% ketoconazole cream, is allowed.
• Known CYP3A substrates with narrow therapeutic index, such as pimozide, quinidine, tacrolimus, cyclosporine, sirolimus, alfentanil, fentanyl (including transdermal patch) or ergot alkaloids (ergotamine, dihydroergotamine).

Sponsors & Collaborators

• Pfizer: lead

Study Sites (12)

The Gujarat Cancer and Research Institute

Ahmedabad, Gujarat, 380016, India

Location

Hemato Oncology Clinic Ahmedabad Pvt. Ltd

Ahmedabad, Gujarat, 380054, India

Location

Artemis hospital

Gurugram, Haryana, 122001, India

Location

National Cancer Institute

Nagpur, Maharashtra, 441108, India

Location

Apex Wellness Hospital

Nashik, Maharashtra, 422009, India

Location

Grant Medical Foundation, Ruby Hall Clinic

Pune, Maharashtra, 411001, India

Location

Sahyadri Clinical Research and Development Center

Pune, Maharashtra, 411004, India

Location

Sahyadri Super Speciality Hospital

Pune, Maharashtra, 411004, India

Location

Bhaktivedanta Hospital and Research Institute

Thane, Maharashtra, 401107, India

Location

Rajiv Gandhi Cancer Institute And Research Centre

New Delhi, National Capital Territory of Delhi, 110085, India

Location

Yashoda Hospital

Hyderabad, Telangana State, 500082, India

Location

Tata Medical Center

Kolkata, West Bengal, 700160, India

Location

Related Links

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

MeSH Terms

Interventions

lorlatinib

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 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 21, 2020
• First Posted: September 9, 2020
• Study Start: August 27, 2020
• Primary Completion: July 20, 2022
• Study Completion: July 20, 2022
• Last Updated: December 20, 2024
• Results First Posted: December 20, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will share

Locations

IN (12)