A Study of Lorlatinib in Advanced ALK and ROS1 Rearranged Lung Cancer With CNS Metastasis in the Absence of Measurable Extracranial Lesions

NCT02927340 | Unknown Phase 2 DMC

• 1 other identifier: 16-248
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

This research study is studying a drug as a possible treatment for ALK-positive or ROS1-positive non-small cell lung cancer (NSCLC). The following drug will be involved in this study :

• Lorlatinib

Conditions

Non-Small Cell Lung Cancer (NSCLC)

Keywords

Lung Cancer

Outcome Measures

Primary Outcomes (1)

• Intracranial Disease Control Rate (DCR)

  DCR will be calculated at 12 weeks based on response assessments in the brain for patients with measurable CNS disease

  12 weeks

Secondary Outcomes (7)

• Median intracranial Progression-Free Survival (PFS)

  2 years

• Time to intracranial (IC) progression

  2 years

• Median Intracranial Duration of Response (DOR)

  2 years

• Median extra-cranial PFS

  2 years

• Median Overall Survival

  2 years

Study Arms (1)

Lorlatinib

EXPERIMENTAL

Lorlatinib will be administered orally once daily on a 21 day cycle Blood will be collected for biomarker studies

Drug: Lorlatinib

Interventions

Lorlatinib DRUG

Lorlatinib

Eligibility Criteria

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

You may qualify if:

• Histologically or cytologically confirmed diagnosis of metastatic NSCLC (Stage IV, American Joint Committee on Cancer v7.0) that carries an ALK rearrangement, as determined by the Food and Drug Administration (FDA)-approved FISH test, using Vysis® ALK Break apart fluorescence in situ hybridization (FISH) Probe Kit (defined as 15% or more positive tumor cells), or the Ventana® immunohistochemistry (IHC) test, or a ROS1 rearrangement as determined by FISH or reverse transcription polymerase chain reaction (RT-PCR) or Next Generation Sequencing (NGS) via a local diagnostic test (LDT).
• ALK positive NSCLC patients must either be treatment naive in the advanced setting or have had disease progression on or intolerance to at least 1 previous ALK inhibitor. ROS1 positive NSCLC patients must either be treatment naive in the advanced setting or have had disease progression on or intolerance to at least 1 previous ROS1 inhibitor.
• Presence of radiographically suspected leptomeningeal disease (LM) or carcinomatous meningitis (CM) AND/OR presence of at least one CNS lesion for which the following criteria are met:
• For patients without leptomeningeal disease: presence of at least one parenchymal CNS lesion that is at least 5 mm in size. Note: Intra-cranial disease assessments can only be performed using contrast-enhanced magnetic resonance imaging (MRI). MRI scan slices of 1 mm are necessary for brain metastases between 5 and 10 mm in size.
• The lesion(s) must be newly diagnosed or be present as progression after local therapy, including surgery and/or radiation therapy. For patients who have received local therapy, progression of pre-existing lesions based on RECIST v1.1 (\>20% increase in longest diameter on baseline scan) or new lesions are required.
• Participants who are receiving corticosteroids must be on a stable or decreasing dose for at least 2 weeks prior to the first dose of study treatment.
• For patients with suspected LM or CM based on imaging, spinal fluid sampling for confirmation is not required. For patients who do undergo spinal fluid sampling, those with negative spinal fluid (CSF) are eligible to enter.
• Age ≥ 18 years
• Eastern Cooperative Oncology Group (ECOG) performance status ≤2 (Karnofsky ≥60%)
• Life expectancy of ≥ 12 weeks, in the opinion of the investigator
• Adequate hematologic function, including:
• Platelet count ≥ 100 x 109/L
• Absolute neutrophil count (ANC) ≥ 1,500/µL
• Hemoglobin ≥ 9 g/dL
• Adequate renal function, including:

You may not qualify if:

• Prior use of lorlatinib (PF-06463922)
• Presence of measurable extracranial disease by RECIST v1.1
• Spinal cord compression is excluded unless the patient demonstrates good pain control attained through therapy and there is stabilization or recovery of neurological function for two weeks prior to study entry.
• Major surgery within 4 weeks of study entry. Minor surgical procedures (eg port insertion, pleurex catheter placement) are not excluded, but sufficient time should have passed for wound healing.
• Radiation therapy (except palliative to relieve bone pain) within 7 days of study entry. Palliative radiation (≤ 10 fractions) must have been completed at least 48 hours prior to study entry. Stereotactic or small field brain irradiation must have been completed at least 7 days prior to study entry. Whole brain radiation must have been completed at least 2 weeks prior to study entry.
• Systemic anti-cancer therapy completed within a minimum of 5 half-lives of study entry.
• Active and clinically significant bacterial, fungal, or viral infection including hepatitis B (HBV), hepatitis C (HCV), known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness.
• Any one of the following currently or in the previous 3 months: myocardial infarction, congenital long QT syndrome, Torsades de Pointes, uncontrolled arrhythmias (including sustained ventricular tachyarrhythmia and ventricular fibrillation), right bundle branch block and left anterior fascicular hemiblock (bifascicular block), unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure (CHF New York Heart Association Classification III or IV) , cerebrovascular accident, transient ischemic attack or symptomatic pulmonary embolism not adequate medically managed with anticoagulants, ongoing cardiac dysrhythmias of CTCAE grade ≥ 2, symptomatic atrial fibrillation of any grade, corrected QT (QTc) interval ≥ 481 msec at screening
• Patients with predisposing characteristics for acute pancreatitis according to investigator judgment (eg current gallstone disease, alcoholism)
• History of extensive, disseminated, bilateral or presence of Grade 3 or 4 interstitial fibrosis or interstitial lung disease including pneumonitis, hypersensitivity pneumonitis, interstitial pneumonia, interstitial lung disease, obliterative bronchiolitis and pulmonary fibrosis. Patients with history of prior radiation pneumonitis are not excluded.
• Participants who are receiving any other investigational agents.
• Active inflammatory gastrointestinal disease or previous gastric resection or lap band.
• Pregnant or lactating women
• Patients with a history of organ transplant including high dose chemotherapy with autologous stem cell rescue
• Current use or anticipated need for food or drugs that are known strong or moderate CYP3A4 inhibitors, including their administration within 10 days prior to the first lorlatinib dose (ie, strong CYP3A4 inhibitors: grapefruit juice or grapefruit/grapefruit related citrus fruits \[eg, Seville oranges, pomelos\], ketoconazole, miconazole, itraconazole, voriconazole, posaconazole, clarithromycin, telithromycin, indinavir, saquinavir, ritonavir, nelfinavir, amprenavir, fosamprenavir nefazodone, lopinavir, troleandomycin, mibefradil, and conivaptan; Moderate CYP3A4 inhibitors: erythromycin, verapamil, atazanavir, delavirdine, fluconazole, darunavir, diltiazem, aprepitant, imatinib, tofisopam, ciprofloxacin, cimetidine)

Sponsors & Collaborators

• Massachusetts General Hospital: lead

Study Sites (1)

Massachusetts general Hospital

Boston, Massachusetts, 02114, United States

RECRUITING

Related Publications (1)

• Dagogo-Jack I, Oxnard GR, Evangelist M, Digumarthy SR, Lin JJ, Gainor JF, Murphy JF, Rabin MS, Heist RS, Muzikansky A, Shaw AT. Phase II Study of Lorlatinib in Patients With Anaplastic Lymphoma Kinase-Positive Lung Cancer and CNS-Specific Relapse. JCO Precis Oncol. 2022 May;6:e2100522. doi: 10.1200/PO.21.00522.

  PMID: 35584349 DERIVED

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Lung Neoplasms

Interventions

lorlatinib

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Ibiayi Dagogo-Jack, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ibiayi Dagogo-Jack, MD

CONTACT

617-724-4000; IDAGOGO-JACK@PARTNERS.ORG

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: September 26, 2016
• First Posted: October 7, 2016
• Study Start: October 1, 2016
• Primary Completion: January 1, 2022
• Study Completion: May 1, 2023
• Last Updated: March 9, 2021

Record last verified: 2021-01

Locations

US (1)