Safety and Efficacy of Cryoablation With Karelizumab and Apatinib for Multiple Lung Cancers

An Exploratory Study of the Safety and Efficacy of Cryoablation in Combination With Karelizumab and Apatinib for the Treatment of Multiple Primary Lung Cancers Without Known Driver Genes

The goal of this clinical trial is to explore the safety and efficacy of cryoablation combined with carlizumab and apatinib in multiple primary lung cancer without known driver genes.Main included population criteria:Clinical and pathological diagnosis of multiple primary lung cancer;Three pulmonary nodules were diagnosed initially or before surgery, without lymph node metastasis;Male or female is 18 years old, and 75 years old;Up to one surgical resection treatment with 2 remaining pulmonary nodules, and postoperative pathology confirmed MIA or AIS and so on.The main questions it aims to answer is safety of cryoablation combined with carilizumab and apatinib in multiple primary lung cancer.Participants will take carplus with apatinib started 2-3 weeks after cryoablation. Carelizumab 200mg, q3w, apatinib 250mg, qd. Every 3 weeks is for one treatment cycle. Until PD, intolerable toxicity, death, patient withdrawal or investigator discretion requires termination.

Study Overview

• Status: Recruiting
• Conditions: Lung Cancer
• Intervention / Treatment: Drug: Karelizumab+Apatinib

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Chengzhi Zhou, Doctor; Phone Number: 13560351186; Email: doctorzcz@163.com
• Study Contact Backup: Name: Xiaohong Xie, master; Phone Number: 13632326736; Email: gyxxh@126.com

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510145
      • Recruiting
      • Chengzhi Zhou
      • Contact: Xiaohong Xie, Master

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Clinical and pathological diagnosis of multiple primary lung cancers；
2. There were 3 intrapulmonary nodules ≥ the initial diagnosis or preoperative, and there was no lymph node metastasis；
3. The maximum lesion diameter ≤ 3 cm；
4. At most, patients has undergone surgical resection treatment, and there are ≥ 2 remaining intrapulmonary nodules, and the postoperative pathology confirms that it is MIA or AIS；
5. It is estimated that at least 1 measurable lesion meeting RECIST v1.1 criteria will remain after cryotherapy；
6. Male or female≥ 18 years old and ≤ 75 years old；
7. United States Eastern Cooperative Oncology Group Performance Status (ECOG PS) score of 0 or 1；
8. Expected survival ≥ 12 weeks；
9. Vital organ and bone marrow function meets the following requirements:a.Blood routine: absolute neutrophil count (ANC) ≥1.5× 109/L, platelet (PLT) ≥100× 109/L, hemoglobin (HGB) ≥9 g/dL;b.Liver function: serum total bilirubin (TBIL) ≤1.5 times the upper limit of normal (ULN), alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) ≤2.5 times the ULN, serum albumin (ALB) ≥2.8 g/dL;c.Renal function: serum creatinine (Cr) ≤ 1.5 x ULN, or creatinine clearance ≥ 40 mL/min;
10. Subject with subject sexual partner needs to use one medically approved contraceptive measure (such as intrauterine device, birth control pill or condom, etc.) during study treatment and for 6 months after the end of the study treatment period;
11. Subjects must have signed an IRB/IEC-approved written informed consent form in accordance with competent authority and study site guidelines and be able to comply with protocol-specified visits, treatment protocols, laboratory tests, and related procedures.

Exclusion Criteria:

1. Patients with known EGFR mutations, ALK rearrangements;
2. Conditions that cannot be treated with cryoablation: diffuse lesions in both lungs, extensive pleural metastases with large pleural effusions, tumors adjacent to or encircling large mediastinal vessels, etc;
3. Prior receipt of anti-PD-1, anti-PD-L1, anti-CTLA-4 antibodies, or any other antibody or drug targeting T cell co-stimulation or immune checkpoint pathways;
4. Received the following treatments:a.Received systemic anti-tumor therapy such as chemotherapy, targeted therapy, immunotherapy, etc. within 4 weeks prior to randomization;b.Treatment with any investigational drug within 4 weeks prior to randomization;c.Receipt of high-dose immunosuppressive medications (systemic glucocorticoids greater than 10 mg/day of prednisone or its equivalent) within 4 weeks prior to randomization;d.Major surgery (such as open, thoracotomy, or laparotomy, etc.), or unhealed surgical wounds, ulcers, or fractures within 4 weeks prior to randomization.
5. Known or suspected active autoimmune disease (congenital or acquired);
6. Known allogeneic organ transplantation (other than corneal transplantation) or allogeneic hematopoietic stem cell transplantation;
7. Hypersensitivity to any component of the monoclonal antibody preparation;
8. With interstitial lung disease;
9. With other uncontrolled serious medical conditions;
10. Other acute or chronic illness, psychiatric illness, or abnormal laboratory test values that may result in an increase in the risk associated with study participation or study drug administration, or interfere with the interpretation of study results, and the patient is listed as ineligible for this study in the judgment of the investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental group; Patients were started on Carrelizumab in combination with Apatinib 2-3 weeks after cryoablation. Karelizumab 200 mg, q3w, and Apatinib 250 mg, qd. Every 3 weeks is a treatment cycle.	Drug: Karelizumab+Apatinib; Karelizumab 200mg, q3w, and Apatinib 250mg, qd. every 3 weeks as a treatment cycle.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
irAEs rate	Incidence of adverse events occurring during treatment	3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ORR	Proportion of patients whose tumor volume shrinks to a pre-specified value and who can maintain the minimum timeframe requirement, as the sum of the proportion in complete and partial remission	3 years
DCR	Number of cases in remission (PR+CR) and stable lesions (SD) after treatment as a percentage of evaluable cases	3 years
DOR	the time between the first time a subject in confirmed complete remission (CR) or confirmed partial remission (PR) reaches confirmed complete remission (CR) or confirmed partial remission (PR) and the time of the first disease progression or death of any cause	3 years
PFS	Time from start of patient's treatment to disease progression or death from any cause	3 years
OS	Time from patient randomization to patient death from any cause	3 years

Collaborators and Investigators

• Sponsor: Zhou Chengzhi
• Investigators: Study Director: Chengzhi Zhou, doctor, The First Affiliated Hospital of Guangzhou Medical University,Guangzhou

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2024
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): August 1, 2027

Study Registration Dates

• First Submitted: September 11, 2024
• First Submitted That Met QC Criteria: September 18, 2024
• First Posted (Actual): September 23, 2024

Study Record Updates

• Last Update Posted (Actual): October 15, 2024
• Last Update Submitted That Met QC Criteria: October 9, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Apatinib
• Other Study ID Numbers: CROC-24-08

Drug and device information, study documents

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