Lorlatinib as Neoadjuvant Treatment in Stage IB-IIIB ALK-rearranged Non-Small Cell Lung Cancer

NCT06682884 | Not Yet Recruiting Phase 2

• 1 other identifier: 2024PHD022-002
• Study Type: interventional
• Target: 25
• Locations: 0 countries
• Sites: N/A

Brief Summary

This project was designed To explore the pathological complete response (pCR) of lorlatinib as neoadjuvant treatment. Twenty-five patients will be involved in this study. These patients will receive lorlatinib neoadjuvant therapy for 6-8 weeks (determined by clinicians' decision based on clinical practice) and then underwent surgery. Previous small-sample clinical studies on ALK inhibitors as neoadjuvant therapy in resectable NSCLC have shown promising outcomes including MPR and pCR, supporting the potential of ALK TKIs in this setting.

Conditions

Neoadjuvant Non-Small Cell Lung Cancer

Keywords

NSCLC; Neoadjuvant; ALK-rearranged; Lorlatinib

Outcome Measures

Primary Outcomes (1)

• Pathologic Complete Response (pCR) Rate

  Pathologic complete response (pCR) rate is defined as the percentage of participants with no residual viable tumor in lung primary or lymph nodes as evaluated by systematic pathological review of surgical specimens.

  Within 1 month after surgery

Secondary Outcomes (6)

• Objective response rate

  Within 1 month after surgery

• Major Pathologic Response (MPR) Rate

  Within 1 month after surgery

• Rate of lymph node downstaging

  within 3 days after the last CT scan before surgery perfomed

• The delay of operation

  The 3rd day of post-operation

• The completion rate of operation

  The 3rd day of post-operation

Study Arms (1)

Lorlatinib as Neoadjuvant Treatment

EXPERIMENTAL

These patients will receive lorlatinib neoadjuvant therapy for 6-8 weeks (determined by clinicians' decision based on clinical practice) and then underwent surgery

Drug: Lorlatinib 100 mg

Interventions

Lorlatinib 100 mg DRUG

Eligible patients will be registered to receive oral lorlatinib 100mg qd for 6-8 weeks each during the neoadjuvant therapy phase

Also known as: third generation ALK- TKI

Lorlatinib as Neoadjuvant Treatment

Eligibility Criteria

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

You may qualify if:

• Aged ≥18 years
• Imaging confirmed, resectable stage IB, II, IIIA or selected IIIB (including T4N2，per AJCC 8th edition)
• Histologically/cytologically confirmed lung adenocarcinoma
• Documented ALK-rearrangement mutation positive (assessed by a local laboratory)
• ECOG PS 0-1
• Patients must be treatment-naive for NSCLC and eligible to receive treatment with Lorlatinb.
• Measurable disease, as defined by RECIST v1.1
• Hematology, liver and kidney function are adequate for neoadjuvant therapy.
• Cardiopulmonary function suitable for surgical treatment (ECG, echocardiography, pulmonary function or blood gas analysis).
• Male participants must be willing to use acceptable methods of contraception.
• Female participants of childbearing potential must agree to use acceptable methods of contraception.
• Ability to provide written informed consent.

You may not qualify if:

• Mixed squamous cell carcinoma, large cell carcinoma, small cell lung cancer.
• Prior treatment with any systemic anti-cancer therapy for locally advanced NSCLC
• Non-resectable stage IB, II, IIIA or selected IIIB NSCLC evaluated by thoracic surgeons.
• Unable to tolerate curative surgery per anaesthesiologist evaluation.History of organ transplant.
• Pregnant or lactating, or intending to become pregnant during the study
• Evidence of any severe or uncontrolled systemic disease, including uncontrolled hypertension and active bleeding, that the investigator considers to be detrimental to patient participation in the study or to adherence to the protocol.
• Past medical history of Interstitial lung disease (ILD), drug-induced ILD, radiation pneumonitis which required steroid treatment, or any evidence of clinically active ILD.
• A clear past history of neurological or psychiatric disorders, including epilepsy or dementia;
• Judgement by investigator that the subject should not participate in the study if the subject is unlikely to comply with the study procedures, restrictions and requirements.

Sponsors & Collaborators

• Peking University People's Hospital: lead
• Hunan Cancer Hospital: collaborator
• Liaoning Cancer Hospital & Institute: collaborator
• Air Force Military Medical University, China: collaborator
• Second Affiliated Hospital, School of Medicine, Zhejiang University: collaborator

Related Publications (1)

• Shaw AT, Felip E, Bauer TM, Besse B, Navarro A, Postel-Vinay S, Gainor JF, Johnson M, Dietrich J, James LP, Clancy JS, Chen J, Martini JF, Abbattista A, Solomon BJ. Lorlatinib in non-small-cell lung cancer with ALK or ROS1 rearrangement: an international, multicentre, open-label, single-arm first-in-man phase 1 trial. Lancet Oncol. 2017 Dec;18(12):1590-1599. doi: 10.1016/S1470-2045(17)30680-0. Epub 2017 Oct 23.

  PMID: 29074098 BACKGROUND

Related Links

• Phase 1 trial of Lorlatinib for ALK/ROS1 NSCLC patients.

MeSH Terms

Interventions

lorlatinib

Study Officials

• Fan F Yang, M.D.

  Peking University People's Hospital

  STUDY CHAIR

Central Study Contacts

Fan F Yang, M.D.

CONTACT

+86-010-88326657; yangfan@pkuph.edu.cn

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: Professor of Thoracic Surgery

Model Details: Lorlatinib as Neoadjuvant Treatment in Stage IB-IIIB ALK-rearranged Non-Small Cell Lung Cancer

Study Record Dates

• First Submitted: November 7, 2024
• First Posted: November 12, 2024
• Study Start: November 15, 2024
• Primary Completion: April 30, 2026
• Study Completion (Estimated): May 31, 2027
• Last Updated: November 12, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share