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

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Brief Title

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

Official Title

SINGLE-ARM STUDY TO EVALUATE THE SAFETY OF LORLATINIB IN ALK INHIBITOR-TREATED UNRESECTABLE ADVANCED AND/OR RECURRENT ALK-POSITIVE NON-SMALL CELL LUNG CANCER PARTICIPANTS IN INDIA

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.
    


Study Phase

Phase 4

Study Type

Interventional


Primary Outcome

Incidence of Adverse events (AEs)

Secondary Outcome

 Percentage of Participants With Objective Responses based on Investigators' assessments

Condition

Advanced Non-Small Cell Lung Cancer

Intervention

Lorlatinib

Study Arms / Comparison Groups

 Lorlatinib
Description:  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.

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

100

Start Date

August 27, 2020

Completion Date

December 20, 2023

Primary Completion Date

December 20, 2023

Eligibility Criteria

        Inclusion Criteria:

          1. 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.

          2. 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.

          3. 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.

          4. Age ≥18 years.

          5. Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1, or 2.

          6. Adequate hematologic and renal function as defined as:

               1. Absolute neutrophil count (ANC) ≥1,000/mm3;

               2. Platelets ≥50,000/mm3;

               3. Hemoglobin ≥8 g/dL;

               4. Estimated creatinine clearance ≥30 mL/min as calculated using the method standard
                  for the institution.

          7. Adequate liver function, including:

               1. Total serum bilirubin ≤1.5 × upper limit of normal (ULN);

               2. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 × ULN
                  (≤5.0 × ULN in case of liver metastases).

          8. Adequate pancreatic function, including:

               1. Serum total amylase ≤1.5 × ULN.*

               2. Serum lipase <1.5 × ULN. *if total amylase >1.5 × ULN, but pancreatic amylase is
                  within the ULN, the participant may be enrolled.

          9. Acute effects of any prior therapy 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 participant.

         10. Systemic anticancer therapy completed within a minimum of 5 half-lives of study
             enrollment (unless clinically meaningful tumor flare per discretion of the
             Investigator, in which discussion with the Sponsor is warranted).

         11. Evidence of a personally signed and dated informed consent document indicating that
             the participant (or a legally acceptable representative) has been informed of all
             pertinent aspects of the study.

         12. Willingness and ability to comply with the study scheduled visits, treatment plans,
             laboratory tests and other procedures.

         13. Pregnancy test for females of childbearing potential negative at Screening or female
             participants who are not of childbearing potential. Male and female participants of
             childbearing potential and at risk for pregnancy must agree to use a highly effective
             method of contraception from the time of Screening, throughout the study and for 3
             months after the last dose of assigned treatment, 6 months if female participants.

        Exclusion Criteria:

          1. 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.

          2. 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.

          3. Known prior or suspected severe hypersensitivity to study drug or any component in its
             formulation.

          4. Active and clinically significant bacterial, fungal, or viral infection.

          5. 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:

               1. Arterial disease such as cerebral vascular accident/stroke (including transient
                  ischemic attack [TIA]), myocardial infarction, unstable angina;

               2. Venous diseases such as cerebral venous thrombosis, symptomatic pulmonary
                  embolism;

               3. 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.

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

          7. 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.

          8. 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.

          9. 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:

               1. Known strong cytochrome (CYP)3A inducers (eg, carbamazepine, enzalutamide,
                  mitotane, rifampin, St. John's Wort).

               2. 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.

               3. Known CYP3A substrates with narrow therapeutic index, such as pimozide,
                  quinidine, tacrolimus, cyclosporine, sirolimus, alfentanil, fentanyl (including
                  transdermal patch) or ergot alkaloids (ergotamine, dihydroergotamine).

               4. Known permeability glycoprotein (P-gp) substrates with a narrow therapeutic index
                  (eg, digoxin).

         10. Participants who are investigational site staff members directly involved in the
             conduct of the study and their family members, site staff members otherwise supervised
             by the Investigator, or participants who are Pfizer employees directly involved in the
             conduct of the study.

         11. Participation in other studies involving investigational drug(s) (Phases 1-4) during
             study participation.

         12. Breastfeeding female participants.
      

Gender

All

Ages

18 Years - N/A

Accepts Healthy Volunteers

No

Contacts

Pfizer CT.gov Call Center, 1-800-718-1021, [email protected]

Location Countries

India

Location Countries

India

Administrative Informations


NCT ID

NCT04541706

Organization ID

B7461030


Responsible Party

Sponsor

Study Sponsor

Pfizer


Study Sponsor

Pfizer CT.gov Call Center, Study Director, Pfizer


Verification Date

September 2020