Trial Title:
Stereotactic Body Radiotherapy Combined With Cadonilimab for Advanced Refractory Malignant Solid Tumors
NCT ID:
NCT05915481
Condition:
Advanced Solid Tumor
Stereotactic Body Radiotherapy
Immune Checkpoint Inhibitor
Safety
Efficacy
Conditions: Official terms:
Neoplasms
Immune Checkpoint Inhibitors
Conditions: Keywords:
Advanced Solid Tumor
Stereotactic body radiotherapy (SBRT)
Immune Checkpoint Inhibitor (ICI)
programmed cell death protein 1 (PD-1)
Cytotoxic T lymphocyte associate protein-4 (CTLA-4)
Study type:
Interventional
Study phase:
Phase 1/Phase 2
Overall status:
Not yet recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Masking description:
Participants will receive SBRT combined with Cadonilimab until disease progression or
intolerable toxicities or death.
Intervention:
Intervention type:
Drug
Intervention name:
Cadonilimab
Description:
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.
Arm group label:
SBRT plus Cadonilimab
Other name:
Immune check point inhibitors
Intervention type:
Radiation
Intervention name:
Stereotactic body radiotherapy
Description:
Participants will receive SBRT to one lesion or more lesions.
Arm group label:
SBRT plus Cadonilimab
Other name:
SBRT
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.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Signed written informed consent;
2. Male or female aged ≥ 18 years and ≤ 75 years;
3. Patients with advanced refractory solid tumors who had previously received standard
treatment;
4. 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;
5. The physical state score (ECOG PS) of the eastern tumor cooperative group was 0 ~ 1;
6. Expected survival time ≥3 months;
7. Laboratory results during screening must meet the following requirements:
1. 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);
2. 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.
3. 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;
4. International standardized ratio (INR) ≤1.5 times ULN and partial prothrombin
time (PTT) or activated partial thrombin time (APTT) ≤1.5 times ULN during the
7 days prior to treatment;
8. For female subjects of reproductive age, urine or serum pregnancy tests should be
negative within 3 days prior to receiving the first study drug administration (Cycle
1, day 1). If the urine pregnancy test results cannot be confirmed negative, a blood
pregnancy test is requested;
9. Compliance with the research protocol is expected to be good.
Exclusion Criteria:
1. 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;
2. 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;
3. 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;
4. 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;
5. Had a large or medium surgery within 4 weeks prior to initial administration, or had
a current unhealed surgical incision, ulcer, or fracture;
6. Had minor surgery (e.g., outpatient/inpatient surgery with local anesthesia) within
48 hours prior to first receiving the study drug;
7. 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);
8. There is a history of non-infectious pneumonia requiring glucocorticoid therapy or a
current interstitial lung disease within 1 year prior to initial administration;
9. 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;
10. 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;
11. has not fully recovered from toxicity and/or complications caused by any
intervention before starting treatment (i.e., ≤ grade 1 or at baseline level,
excluding weakness or hair loss);
12. Treated uncontrolled hypertension (systolic blood pressure greater than 140 mmHg
and/or diastolic blood pressure greater than 90 mmHg), a history of hypertensive
crisis or hypertensive encephalopathy; Uncontrolled hyperglycemia after treatment ;
13. Patients with clinically uncontrollable third space effusion (such as pleural
effusion/pericardial effusion, who do not need drainage effusion or have no
significant increase of effusion after 3 days of stopping drainage can be included
in the group);
14. Any unstable systemic disease, including but not limited to active infections,
congestive heart failure [New York Heart disease Association(NYHA) classification ≥
II], severe arrhythmias requiring medication, liver, kidney, or metabolic disease;
Type I and type II respiratory failure; The tumor compresses important organs (such
as esophagus), compresses superior vena cava or invades mediastinal great vessels,
heart, etc. A previous history of gastrointestinal perforation and/or fistula,
intestinal obstruction, extensive enterectomy, Crohn's disease, ulcerative colitis,
or long-term chronic diarrhea within 6 months;
15. Have received solid organ or blood system transplantation, except corneal
transplantation;
16. Known history of human immunodeficiency virus (HIV) infection (i.e. HIV 1/2 antibody
positive), known active syphilis;
17. Tuberculosis that is active or currently requiring medical intervention, including
but not limited to tuberculosis;
18. Untreated active hepatitis B;
19. Subjects with active hepatitis C virus (HCV) infection (HCV antibody positive and
HCV-RNA level above the lower limit of detection);
20. had other malignancies within 5 years of randomization except for adequately treated
cervical carcinoma in situ, basal cell or squamous cell skin cancer, local prostate
cancer after radical surgery, ductal carcinoma in situ after radical surgery, or
papillary thyroid cancer;
21. Known severe allergic reactions (≥ grade 3) to the active ingredient and/or any
excipients of Cadonilimab;
22. Women who are pregnant or lactating or who plan to become pregnant or lactating
during the study period;
23. For men or women at risk of conception, use of highly effective birth control during
the study period of drug use and within 90 days after the last dose is not intended.
24. A history of alcohol or drug abuse;
25. Conditions deemed unsuitable for inclusion by other researchers.
Gender:
All
Minimum age:
18 Years
Maximum age:
75 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Department of radiation oncology, Peking University Third Hospital
Address:
City:
Peking
Zip:
100191
Country:
China
Contact:
Last name:
Hongqing Zhuang, M.D.
Phone:
8601082264910
Email:
hongqingzhuang@163.com
Contact backup:
Last name:
Yi Chen, M.D.
Phone:
8601082264910
Email:
bruce_tsinghua@163.com
Start date:
June 21, 2023
Completion date:
June 21, 2025
Lead sponsor:
Agency:
Peking University Third Hospital
Agency class:
Other
Source:
Peking University Third Hospital
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05915481
