Clinical Study of Stereotactic Body Radiotherapy Combined With Cadonilimab for the Treatment of Advanced Refractory Malignant Solid Tumors
Overview
- Phase
- Phase 1
- Intervention
- Cadonilimab
- Conditions
- Advanced Solid Tumor
- Sponsor
- Peking University Third Hospital
- Enrollment
- 60
- Locations
- 1
- Primary Endpoint
- Adverse event(AE)
- Status
- Not Yet Recruiting
- Last Updated
- 2 years ago
Overview
Brief Summary
The goal of this multicenter prospective single-arm phase I/II study is to study the safety and efficacy stereotactic body radiotherapy (SBRT) combined with Cadonilimab for advanced refractory malignant solid tumors. The main questions it aims to answer are:
- How safe is this regimen of SBRT combined with Cadonilimab for advanced refractory malignant solid tumors?
- How effective is this regimen of SBRT combined with Cadonilimab for advanced refractory malignant solid tumors? Participants will receive SBRT combined with Cadonilimab until disease progression or intolerable toxicities or death.
Detailed Description
The goal of this single center prospective single-arm phase I/II study is to study the safety and efficacy stereotactic body radiotherapy (SBRT) combined with Cadonilimab for advanced refractory malignant solid tumors. The primary endpoint is adverse event (AE) and the secondary endpoints are progression free survival, overall survival, overall response rate, and disease control rate. Participants will receive SBRT combined with Cadonilimab. Cadonilimab will be administered, 6mg/kg, twice a week, intravenous until disease progression or intolerable toxicities or death. The first cycle of Cadonilimab was started within 3 days before and after the first fraction of SBRT treatment.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Signed written informed consent;
- •Male or female aged ≥ 18 years and ≤ 75 years;
- •Patients with advanced refractory solid tumors who had previously received standard treatment;
- •At least one measurable lesion must be used as a target lesion (according to RECIST V1.1). Measurable lesions located in the radiation field of previous radiotherapy or after local treatment can also be selected as a target lesion if progression is confirmed;
- •The physical state score (ECOG PS) of the eastern tumor cooperative group was 0 \~ 1;
- •Expected survival time ≥3 months;
- •Laboratory results during screening must meet the following requirements:
- •Blood routine: neutrophil absolute count (ANC) ≥ 1.5 × 109/L, platelet count (PLT) ≥ 100 × 109/L, hemoglobin (HGB) ≥ 90 g/L (no blood transfusion or erythropoietin dependence within 7 days);
- •Liver function: total bilirubin (TBIL) ≤ 1.5 times the upper limit of normal value (ULN); Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were less than 2.5 times ULN in subjects without liver metastasis, and ALT and AST were less than 5 times ULN in subjects with liver metastasis.
- •Renal function: serum creatinine (Cr) ≤1.5 times ULN or Cr clearance ≥60 mL/min (Cockcroft-Gault formula), and urine protein (UPRO) \< on routine urine test; 2+ or 24 h urinary protein quantification \< 1g;
Exclusion Criteria
- •Patients are currently participating in an interventional clinical study, or has received other investigational drugs or been treated with investigational instruments within 4 weeks prior to initial dosing;
- •Systemic treatment with Chinese herbal medicine or immunomodulatory drugs (including thymosin, interferon and interleukin, except for local use to control pleural efflux) with anti-tumor indications within 2 weeks prior to initial administration;
- •Received palliative radiotherapy within 7 days prior to initial administration. Patients who had received palliative radiotherapy before 7 days prior to initial administration had to meet all of the following criteria to be enrolled: there was no current toxicity associated with radiotherapy and no need for glucocorticoids;
- •Received live attenuated vaccine within 4 weeks prior to initial administration (or planned to receive live vaccine during the study period); Note: Inactivated virus vaccines for injectable seasonal influenza are permitted for up to 4 weeks prior to initial administration; But live attenuated influenza vaccines are not allowed;
- •Had a large or medium surgery within 4 weeks prior to initial administration, or had a current unhealed surgical incision, ulcer, or fracture;
- •Had minor surgery (e.g., outpatient/inpatient surgery with local anesthesia) within 48 hours prior to first receiving the study drug;
- •Receiving any other form of immunosuppressive therapy within 7 days prior to initial administration of the study, excluding nasal spray, inhalation or other routes of topical corticosteroids or physiological doses of systemic corticosteroids (≤10 mg/ day of prednisone or equal doses of drugs);
- •There is a history of non-infectious pneumonia requiring glucocorticoid therapy or a current interstitial lung disease within 1 year prior to initial administration;
- •An active autoimmune immune disease requiring systemic therapy (e.g., disease-modifying drugs, corticosteroids, or immunosuppressants) has occurred within 2 years prior to initial administration. Alternative therapies (such as thyroxine, insulin, or physiological corticosteroids for adrenal or pituitary insufficiency) are not considered systemic therapy;
- •symptomatic central nervous system metastasis; Patients with asymptomatic brain metastases or stable symptoms for ≥2 weeks after treatment were eligible to participate in this study if they met all of the following criteria: measurable lesions outside the central nervous system; No meningeal, midbrain, pons, cerebellum, bulbar, or spinal cord metastasis; No history of intracranial hemorrhage; Stop hormone therapy 14 days before the first dose of the study drug;
Arms & Interventions
SBRT plus Cadonilimab
Participants will receive SBRT combined with Cadonilimab. Cadonilimab will be administered, 6mg/kg, twice a week, intravenous until disease progression or intolerable toxicities or death. The first cycle of Cadonilimab was started within 3 days before and after the first fraction of SBRT treatment.
Intervention: Cadonilimab
SBRT plus Cadonilimab
Participants will receive SBRT combined with Cadonilimab. Cadonilimab will be administered, 6mg/kg, twice a week, intravenous until disease progression or intolerable toxicities or death. The first cycle of Cadonilimab was started within 3 days before and after the first fraction of SBRT treatment.
Intervention: Stereotactic body radiotherapy
Outcomes
Primary Outcomes
Adverse event(AE)
Time Frame: 12 weeks
The incidence of All adverse event (AE), treatment emergent AE (TEAE), treatment-related AE (TRAE), immune-related AE (irAE), serious AE (SAE) and radiation-related AE(rAE), the relevance and severity related with the study protocol.
Secondary Outcomes
- Overall response rate(ORR)(12 weeks)
- Overall survival(OS)(12 weeks)
- Progression-free survival(PFS)(12 weeks)
- Disease control rate(DCR)(12 weeks)