ALK Tyrosine Kinase Inhibitors in ALK-rearranged Advanced Squamous Cell Carcinoma

NCT05014464 | Recruiting Phase 2

• 1 other identifier: 20210119
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 1

Brief Summary

This study was to explore the efficacy of ALK-TKI in lung squamous cell carcinoma. Approximately 5% of lung adenocarcinomas have oncogenic fusions of EML-4 and ALK a mutation associated with tumorigenesis and migration.

Conditions

Non-small Cell Lung Cancer

Keywords

ALK rearrangement; Squamous cell lung cancer; ALK-TKI

Outcome Measures

Primary Outcomes (1)

• Progression-free survival (PFS)

  To assess progression-free survival of patients treated by different treatment according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 by investigator, define as first dose to first documented disease progression assessed by investigator or death due to any cause

  Time from first subject dose to study completion, or up to 36 month

Secondary Outcomes (2)

• Overall survival (OS)

  Time from first subject dose to study completion, or up to 36 month.

• Objective Response Rate (ORR)

  Time from first dose to last dose, or up to 24 month.

Study Arms (3)

Cohort A, first line ALK-TKIs

EXPERIMENTAL

All the patients were treated with first line ALK-TKis including Crizotinib, Alectinib, Brigatinib and Lorlatinib etc. Approximately 30 patients.

Drug: Crizotinib

Cohort B, second line ALK-TKIs

EXPERIMENTAL

All the patients were treated with second line ALK-TKis including Crizotinib, Alectinib, Brigatinib and Lorlatinib etc. Approximately 30 patients.

Drug: Crizotinib

Cohort C, post second line ALK-TKIs

EXPERIMENTAL

All the patients were treated with post second ALK-TKis including Crizotinib, Alectinib, Brigatinib and Lorlatinib etc. Approximately 30 patients.

Drug: Crizotinib

Interventions

Crizotinib DRUG

Crizotinib 250mg po bid Aectinib 600mg po bid Lorlatinib 100mg po qd Brigatinib, 90mg po qd for one week and than 180mg po qd forever Pemetrexed 500mg/m2

Also known as: Alectinib, Brigatinib, Lorlatinib, Pemetrexed, immune checkpoint inhibitors, Carboplatin, Paclitaxel

Cohort A, first line ALK-TKIs; Cohort B, second line ALK-TKIs; Cohort C, post second line ALK-TKIs

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Understand the requirements and contents of the clinical trial, and provide a signed and dated informed consent form.
• Age ≥ 18 years.
• Histopathology or cytology confirmed and recorded local progression or metastatic Advanced Squamous Cell Carcinoma without systemic treatment.
• ALK fusion positive evaluated by IHC (ventana), NGS or FISH.
• ECOG 0 - 1.
• Predicted survival ≥ 12 weeks.
• Adequate bone marrow hematopoiesis and organ function
• Presence of measurable lesions according to RECIST 1.1.
• Subjects with stable brain metastases may be included in the study.

You may not qualify if:

• Prior systemic therapy for locally advanced or metastatic disease.
• Subjects who have received any of the following treatments must be excluded:
• Treatment with molecules such as EGFR, VEGFR antibodies within 4 weeks prior to the first dose of study drug.
• Have received radiation within 14 days prior to the first dose or have not recovered from radiation-related toxicity. Chest and extra-brain palliative radiotherapy, stereotactic radiosurgery, and stereotactic body radiotherapy may be performed 7 days prior to the first dose.
• Ongoing (or inability to discontinue) possibly potent CYP1A2, CYP3A inhibitor (1 week), or inducer (2 weeks) drug therapy or herbal supplements within 1-2 weeks prior to the first dose.
• Presence of spinal cord compression or meningeal metastasis.
• History of other malignant tumors within 2 years.
• Adverse events (except alopecia of any degree) of CTCAE \> grade 1 due to prior treatment (e.g., adjuvant chemotherapy, radiotherapy, etc.) prior to the first dose.
• History of stroke or intracranial hemorrhage within 6 months prior to the first dose.
• The presence of any severe or poorly controlled systemic disease, including poorly controlled hypertension and active bleeding in the judgment of the investigator.
• Subjects with persistent or active infection, including but not limited to hepatitis B (HBV), hepatitis C (HCV), human immunodeficiency virus (HIV) and COVID-19 infection.
• Heart-related diseases or abnormalities
• Past history of interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonitis requiring steroid therapy or interstitial lung disease with active clinical symptoms, immune pneumonia caused by immunotherapy.
• Refractory nausea and vomiting, chronic gastrointestinal disease, difficulty swallowing drugs, or inability to adequately absorb sunvozertinib or anlotinib due to previous bowel resection.
• Live vaccine was given 2 weeks before the first medication.

Sponsors & Collaborators

• Hunan Province Tumor Hospital: lead

Study Sites (1)

Hunan Cancer Hospital

Changsha, Hunan, 410013, China

RECRUITING

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Crizotinib; alectinib; brigatinib; lorlatinib; Pemetrexed; Immune Checkpoint Inhibitors; Carboplatin; Paclitaxel

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Aminopyridines; Pyridines; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Antineoplastic Agents, Immunological; Antineoplastic Agents; Therapeutic Uses; Coordination Complexes; Organic Chemicals; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes

Study Officials

• Yongchang Zhang, MD

  Hunan Cancer Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Yongchang Zhang, MD

CONTACT

+8613873123436; zhangyongchang@csu.edu.cn

Nong Yang, MD

CONTACT

+8613873123436; yangnong0217@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, Director of Clinical Trial Center

Study Record Dates

• First Submitted: August 14, 2021
• First Posted: August 20, 2021
• Study Start: November 13, 2021
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): August 8, 2027
• Last Updated: September 20, 2024

Record last verified: 2024-09

Locations

CN (1)