Clinical trial NCT06607770: Safety and Efficacy of Cryoablation With Karelizumab and Apatinib for Multiple Lung Cancers
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Lung Cancer
Lead sponsor: Guangzhou Institute of Respiratory Disease
Sponsor class: OTHER
First posted: 2024-09-23
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: irAEs rate
timeFrame: 3 years
Secondary outcomes:
measure: ORR
timeFrame: 3 years
measure: DCR
timeFrame: 3 years
measure: DOR
timeFrame: 3 years
measure: PFS
timeFrame: 3 years
measure: OS
timeFrame: 3 years
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Chengzhi Zhou
state: Guangdong
Study officials:
affiliation: The First Affiliated Hospital of Guangzhou Medical University,Guangzhou
name: Chengzhi Zhou, doctor
role: STUDY_DIRECTOR
References: