Crizotinb or Standard Chemotherapy in Met Exon 14 Skipping Advanced NSCLC (CONFIRM)

Crizotinb or Standard Chemotherapy in Met Exon 14 Skipping Advanced Non-small Cell Lung Cancer

This study aims to explore the efficacy and safety of Crizotinb or Standard Chemotherapy in Met exon 14 skipping Advanced Non-small Cell Lung Cancer

Study Overview

• Status: Recruiting
• Conditions: Non-small Cell Lung Cancer
• Intervention / Treatment: Drug: Crizotinib; Drug: Pemetrexed

Detailed Description

This study aims to explore the efficacy and safety of Crizotinb or Standard Chemotherapy in Met exon 14 skipping Advanced Non-small Cell Lung Cancer . All the clinical and survival data will be collected for full analysis.

• Study Type: Interventional
• Enrollment (Estimated): 120
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Yongchang Zhang, MD; Phone Number: +861383123436 +8613873123436; Email: zhangyongchang@csu.edu.cn

Study Locations

• China
  • Hunan
    • Changsha, Hunan, China, 410013
      • Recruiting
      • Yongchang Zhang
      • Contact: Yongchang Yongchang Zhang, MD; Phone Number: +8613873123436 +8613873123436; Email: zhangyongchang@csu.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Study Population

Met Exon 14 Skipping Advanced Non-small Cell Lung Cancer Confirmed by NGS

Description

Inclusion Criteria:

1. Understand the requirements and contents of the clinical trial, and provide a signed and dated informed consent form.
2. Age ≥ 18 years.
3. Histopathology or cytology confirmed and recorded local progression or metastatic non-small cell lung cancer without systemic treatment.
4. MET exon 14 skippign confirmed by an accredited local laboratory.
5. ECOG 0 - 1.
6. Predicted survival ≥ 12 weeks.
7. Adequate bone marrow hematopoiesis and organ function
8. Presence of measurable lesions according to RECIST 1.1.
9. Subjects with stable brain metastases may be included in the study.

Exclusion Criteria:

1. Prior systemic therapy for locally advanced or metastatic disease.

2. 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.
3. Presence of spinal cord compression or meningeal metastasis.
4. History of other malignant tumors within 2 years.
5. 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.
6. History of stroke or intracranial hemorrhage within 6 months prior to the first dose.
7. The presence of any severe or poorly controlled systemic disease, including poorly controlled hypertension and active bleeding in the judgment of the investigator.
8. 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.
9. Heart-related diseases or abnormalities
10. 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.
11. Refractory nausea and vomiting, chronic gastrointestinal disease, difficulty swallowing drugs, or inability to adequately absorb sunvozertinib or anlotinib due to previous bowel resection.
12. Live vaccine was given 2 weeks before the first medication.
13. Women who are breastfeeding or pregnant.
14. Hypersensitivity to the test drug and the ingredients.
15. Other conditions assessed by the investigator to be unsuitable for participation in the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort A: Target Therapy Group.; Patients with MET exon 14 skipping will be treated with First line crizotinib or savolitinib and other MET TKIs.	Drug: Crizotinib; Crizotinib 250mg po bid. Savolitinib 300mg po, qd.; Other Names: Savolitinib
Experimental: Cohort B: Chemotherapy or Chemotherapy plus immune checkpoint inhibitor; Patients with MET exon 14 skipping will be treated with chemotherapy.	Drug: Pemetrexed; Pemetrexed, 500mg/m2, ivgtt erery 21day.; Other Names: Bevacizumab; Carboplatin; immune checkpoint inhibitors

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival (PFS)	PFS defines 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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival (OS)	To assess overall survival, define as first dose to the death of the subject due to any cause	Time from first subject dose to study completion, or up to 36 month
Objective Response Rate (ORR)	To assess Chemotherapy and TKIs overall response rate according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 by investigator, define as the proportion of subjects who have a complete response (CR) or a partial response (PR)	Time from first subject dose to study completion, or up to 36 month

Collaborators and Investigators

• Sponsor: Hunan Province Tumor Hospital
• Investigators: Principal Investigator: Yongchang Zhang, MD, Hunan Cancer Hospital

Study record dates

Study Major Dates

• Study Start (Actual): March 24, 2020
• Primary Completion (Estimated): March 24, 2025
• Study Completion (Estimated): March 24, 2026

Study Registration Dates

• First Submitted: March 24, 2020
• First Submitted That Met QC Criteria: March 24, 2020
• First Posted (Actual): March 26, 2020

Study Record Updates

• Last Update Posted (Estimated): June 4, 2024
• Last Update Submitted That Met QC Criteria: June 1, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Keywords: non-small cell lung cancer; Chemotherapy; Crizotinb
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antineoplastic Agents; Antineoplastic Agents, Immunological; Protein Kinase Inhibitors; Folic Acid Antagonists; Tyrosine Kinase Inhibitors; Carboplatin; Pemetrexed; Immune Checkpoint Inhibitors; Crizotinib
• Other Study ID Numbers: 20203017

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No