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Non-Small Cell Lung Cancer (NSCLC)Phase 2NCT02927340

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

A Phase 2 study testing Lorlatinib in people with Non-Small Cell Lung Cancer (NSCLC), run by Massachusetts General Hospital at 1 site in United States.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial 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 Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Non-Small Cell Lung Cancer (NSCLC)
What is being tested?
Lorlatinib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
30 participants
Where
1 siteUnited States
Study dates
Oct 2016to May 2023
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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:
  • Serum creatinine ≤1.5x the upper limit of normal (ULN) or an estimated glomerular filtration rate (eGFR) calculated using the Modification of Diet in Renal Disease (MDRD) equation of at least 45 mL/min/1.73 m2
  • Adequate pancreatic function, including:
  • Serum lipase ≤ 1.5x ULN
  • Adequate liver function, including:
  • Total serum bilirubin ≤ 1.5x ULN
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3.0x ULN in the absence of known metastatic involvement of the liver or AST and ALT ≤ 5.0x ULN if there is metastatic liver involvement.
  • Alkaline phosphatase ≤ 2.5x ULN in the absence of known bone metastases or ≤ 5.0x ULN in the case of bone metastases.
  • After progression on or intolerance to prior ALK or ROS inhibitor therapy:
  • A minimum washout period of at least 5 half-lives between the last dose of ALK or ROS inhibitor therapy and the first dose of study treatment is required. A shorter washout period may be considered in the event of disease flare, after discussion with the Sponsor.
  • Patients must have recovered from treatment toxicities to ≤ Grade 1 or to their pretreatment levels except for adverse events (AEs) that in the investigator's judgment do not constitute a safety risk for the patient.
  • Patients can either be chemotherapy-naive or have received at least one line of platinum-based chemotherapy for locally advanced or metastatic disease. Acute effects of therapy must have resolved to baseline severity or to CTCAE grade ≤1 except for AEs that in the investigator's judgment do not constitute a safety risk for the patient.
  • Recovery from effects of any major surgery or significant traumatic injury at least 28 days before the first dose of study treatment
  • For all women of childbearing potential, a negative pregnancy test must be obtained at the baseline visit before starting study treatment.
  • For women who are not postmenopausal (≥ 12 months of non-therapy-induced amenorrhea) or surgically sterile (absence of ovaries and/or uterus): agreement to remain abstinent or use two adequate methods of contraception, including at least one method with a failure rate of < 1% per year, during the treatment period and for at least 90 days after the last dose of study drug.
  • Abstinence is only acceptable if it is in line with the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or post-ovulation methods) and withdrawal are not acceptable methods of contraception.
  • Examples of contraceptive methods with a failure rate of < 1% per year include tubal ligation, male sterilization, hormonal implants, established, proper use of combined oral or injected hormonal contraceptives, and certain intrauterine devices. Alternatively, two methods (e.g., two barrier methods such as a condom and a cervical cap) may be combined to achieve a failure rate of <1% per year. Barrier methods must always be supplemented with the use of a spermicide.
  • For men: agreement to remain abstinent or use a barrier method of contraception (e.g., condom) during the treatment period and for at least 90 days after the last dose of study drug and agreement to refrain from donating sperm during this same period
  • Men with a pregnant partner must agree to remain abstinent or use a condom for the duration of the pregnancy.
  • Abstinence is only acceptable if it is in line with the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable methods of contraception.
  • Ability to understand and the willingness to sign a written informed consent document.

Who cannot join

  • 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.
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  • 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)
  • Current use or anticipated need for drugs that are known strong CYP3A4 inducers, including their administration within 12 days prior to the first lorlatinib dose (ie, phenobarbital, rifampin, phenytoin, carbamazepine, rifabutin, rifapentin, clevidipine, St. John's Wort).
  • Concurrent use of drugs that are CYP3A4 substrates with narrow therapeutic indices such as astemizole, terfenadine, cisapride, pimozide, quinidine, tacrolimus, cyclosporine, sirolimus, (alfentanil and fentanyl, including transdermal patch) or ergot alkaloids (ergotamine, dihydroergotamine) is not permitted or caution is warranted.
  • Concurrent use of drugs that are CYP2C9 substrates with narrow therapeutic indices, such as warfarin, phenytoin or a sensitive substrate such as celecoxib is not permitted or caution is warranted.
  • Concurrent use of drugs that are sensitive CYP2B6 substrates, such as bupropion, efavirenz is not permitted or caution is warranted.
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to lorlatinib.
  • 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 patient inappropriate for entry into this study.

Trial locations and contacts

1 site in 1 country.

Ibiayi Dagogo-Jack, MD contact

617-724-4000

IDAGOGO-JACK@PARTNERS.ORG

United States1 site, 1 recruiting

  • Massachusetts general Hospital

    Boston, Massachusetts, 02114

    Ibiayi Dagogo-Jack, MD, 617-724-4000, IDAGOGO-JACK@PARTNERS.ORG

    Ibiayi Dagogo-Jack, MD

    Recruiting

Other trials in United States

About this study

Official title: A Phase II Study of Lorlatinib (PF-06463922) in Advanced Anaplastic Lymphoma Kinase (ALK) and ROS Proto-Oncogene 1 (ROS1) Rearranged Non-Small Cell Lung Cancer (NSCLC) With Central Nervous System (CNS) Metastasis in the Absence of Measurable Extracranial Lesions

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
Read the detailed description

This research study is a Phase II clinical trial. Phase II clinical trials test the safety and effectiveness of an investigational drug to learn whether the drug works in treating a specific disease. "Investigational" means that the drug is being studied. The FDA (the U.S. Food and Drug Administration) has not approved Lorlatinib as a treatment for any disease.

All participants in this study will receive Lorlatinib. Lorlatinib targets the abnormal ALK or ROS1 proteins in NSCLC cells. Lorlatinib has been tested in other research studies and results show that the medicine may help to control the growth of NSCLC even after it has spread to the CNS. The CNS is a term used to refer to the brain and spinal cord, including the lining of the brain and spinal cord which is called the meninges.

In this research study, the investigators are trying to determine whether lorlatinib is effective in controlling the growth of cancer cells after they have spread to the CNS. Another purpose of this study is to determine why the cancer cells that have spread to the participant CNS have continued to grow despite treatment with other drugs. For this reason, blood samples will be collected as part of this study to assess the DNA released by the participants cancer cells into their blood when the cells travel to other sites in their body.

Being tested
Lorlatinib
Keywords
Lung Cancer
Medical subject headings
Carcinoma, Non-Small-Cell Lung, Lung Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • LorlatinibDrug

Study groups in NCT02927340
Study groupRoleWhat they receive
LorlatinibExperimentalLorlatinib will be administered orally once daily on a 21 day cycle Blood will be collected for biomarker studies
Receives: Drug: Lorlatinib

What is being measured

The primary outcome is the main question the study is designed to answer.

  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

    Measured: 12 weeks

Secondary outcomes (7)

  1. Median intracranial Progression-Free Survival (PFS)

    Measured: 2 years

  2. Time to intracranial (IC) progression

    Measured: 2 years

  3. Median Intracranial Duration of Response (DOR)

    The distribution function of DOR will be estimated using the Kaplan-Meier method

    Measured: 2 years

  4. Median extra-cranial PFS

    Extra-cranial PFS will be defined as the time from the start of study drug treatment to the date of the first documented progression at an extra-cranial site or death. The distribution of PFS will be estimated using the Kaplan-Meier method.

    Measured: 2 years

  5. Median Overall Survival

    Measured: 2 years

  6. Toxicity assessed using CTCAE v4.0 criteria

    Measured: 2 years

  7. Intracranial Objective Response Rate (ORR)

    Measured: 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted7 Oct 2016 (estimated)
  2. Study startOct 2016
  3. Primary completionJan 2022 (estimated)
  4. Study completionMay 2023 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
30 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02927340
Sponsor's protocol ID
16-248
Status last verified
Jan 2021
First submitted
26 Sep 2016
Last updated
9 Mar 2021
Results posted
No
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 35584349

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Lorlatinib in people with Non-Small Cell Lung Cancer (NSCLC), run by Massachusetts General Hospital at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 35 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 9 Mar 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Ibiayi Dagogo-Jack, MD (617-724-4000, IDAGOGO-JACK@PARTNERS.ORG), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Intracranial Disease Control Rate (DCR) (time frame: 12 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02927340, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Mar 2021.

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