Trial Title:
Efficacy and Safety of Cadonilimab Plus Anlotinib in Advanced STS That Failed the Previous First-line Standard Treatment
NCT ID:
NCT05926700
Condition:
Soft Tissue Sarcoma
Conditions: Official terms:
Sarcoma
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Candonilimab
Description:
The patients were treated with Candonilimab + anlotinib, with Cadonilimab 10mg/kg, D1
administration; Anlotinib 12mg/ day was orally administered for 2 weeks and stopped for a
week, with 21 days as a course of treatment.
Arm group label:
intervention group
Summary:
Objective to evaluate the efficacy and safety of candonilimab combined with anlotinib in
the treatment of progressive or metastatic soft tissue sarcoma that failed previous
first-line standard therapy.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Male or female, aged 18 to 70 years (including 18 and 70).
2. Voluntarily sign written informed consent.
3. Advanced or unresectable soft tissue sarcomas confirmed by pathology mainly include
liposarcoma, leiomyosarcoma, synovial sarcoma, undifferentiated pleomorphic sarcoma
/ malignant fibrous histiocytoma, fibrosarcoma, pleomorphic rhabdomyosarcoma, acinar
soft tissue sarcoma, clear cell sarcoma, angiosarcoma, epithelioid sarcoma,
malignant peripheral nerve sheath tumor, undifferentiated sarcoma, sarcoma after
radiotherapy, etc.
4. Patients who have used at least one chemotherapy regimen (including anthracyclines)
in the past (except for acinar soft tissue sarcoma and clear cell sarcoma) and are
evaluated as disease progression according to the efficacy evaluation criteria of
solid tumors within 6 months.
5. According to RECIST 1.1, there was at least one measurable tumor lesion.
6. ECoG score 0 or 1.
7. The expected survival was ≥ 3 months.
8. The main organs function well:
a) Hematology (no blood components and cell growth factors were used to support
treatment within 7 days before starting the study treatment):
i. The absolute value of neutrophils ANC ≥ 1.5 × 109/l (1500/mm3).
Ii Platelet count ≥ 100 × 109/l (100000/mm3).
III. hemoglobin ≥ 90 g/l.
b) Kidney:
i. Creatinine clearance * (CrCl) calculated value ≥ 50 ml/min.
*The Cockcroft Gault formula will be used to calculate CrCl (Cockcroft Gault
formula)
CrCl (ml/min) = [(140 - age) × Weight (kg) × F] / (SCR (mg/dl) × 72)
Among them, f=1 for men and f=0.85 for women; SCR = serum creatinine.
Ii Urine protein < 2+ or 24-hour (H) urine protein quantification <1.0 G.
c) Liver:
i. Total serum bilirubin (TBIL) ≤ 1.5 × ULN.
II. AST and alt ≤ 2.5 × ULN.
III. for subjects with liver metastasis, serum total bilirubin (TBIL) ≤ 3 × ULN; ALT
and AST ≤ 5 × ULN;
d) Coagulation function:
i. International normalized ratio (INR) and activated partial thromboplastin time
(APTT) ≤ 1.5 × ULN.
9. Female subjects with fertility must have a serum pregnancy test within 3 days before
the first medication and the result is negative. If a female issue with fertility
has sex with a male partner who has not been sterilized, the subject must take an
acceptable contraceptive method since the screening, and must agree to continue
using the contraceptive method within 6 months after the last administration of the
study drug; Whether to stop contraception after this time point should be discussed
with the investigator.
10. The subject is willing and able to comply with the visit, treatment plan, laboratory
test, and other study requirements as stipulated in the schedule.
Exclusion Criteria:
1. Participated in the treatment of experimental drugs or used experimental devices
within 4 weeks before the first administration of candonilimab.
2. Had other active malignancies within 3 years before enrollment. Except for locally
curable malignant tumors (manifested as cured), such as basal or cutaneous squamous
cell carcinoma, superficial bladder cancer, endometrial, cervical or breast cancer
in situ.
3. Another clinical study is enrolled at the same time, unless it is an observational
(non interventional) clinical study or the follow-up period of an interventional
study (defined as the time from the first medication to the last medication of the
previous clinical study is more than 4 weeks or the five half lives of the study
drug are more than 5, whichever is the longest).
4. Active autoimmune diseases requiring systemic treatment within two years before the
start of study treatment, or autoimmune diseases that may recur or are planned to be
treated according to the judgment of the investigator; The following exceptions:
skin diseases that do not need systematic treatment (such as vitiligo, alopecia,
psoriasis or eczema); Hypothyroidism caused by autoimmune thyroiditis only requires
a stable dose of hormone replacement therapy; Well controlled type I diabetes;
Subjects whose asthma in childhood has been completely relieved and who do not need
any intervention after adulthood; The investigator judged that the disease would not
recur without external triggers.
5. Inflammatory bowel disease (such as Crohn's disease, ulcerative colitis, or chronic
diarrhea) with active or requiring clinical treatment.
6. The subject required systemic treatment with corticosteroids (>10mg daily prednisone
equivalent) or other immunosuppressive drugs within 14 days after taking the study
drug. In the absence of active autoimmune disease, inhaled or topical steroids and
adrenal gland replacement doses of >10mg daily prednisone equivalent were allowed.
Subjects were allowed to use topical, ocular, intra-articular, intranasal, and
inhaled corticosteroids (with minimal systemic absorption). Physiological
alternative doses of systemic corticosteroids are allowed, even if >10 mg / day of
prednisone equivalent. Short term use of corticosteroids is allowed to prevent (such
as contrast allergy) or treat non autoimmune diseases (such as delayed type
hypersensitivity caused by contact allergens).
7. He has previously received immune checkpoint inhibitors (such as anti-PD-1 antibody,
anti-PD-L1 antibody, anti-CTLA-4 antibody, etc.), immune checkpoint agonists (such
as antibodies against ICOS, CD40, CD137, GITR, OX40 targets, etc.), immune cell
therapy and other treatments targeting tumor immune mechanism.
8. The best swelling evaluation result of patients who had received previous treatment
with anlotinib was PD, or SD ≤ 12 weeks.
9. History of a known positive test for human immunodeficiency virus or known acquired
immune deficiency syndrome.
10. Known history of allogeneic organ transplantation and allogeneic hematopoietic stem
cell transplantation.
11. Known presence or history of interstitial lung disease.
12. Necrotic lesions were found within 4 weeks before the subjects were enrolled, and
the investigator judged that there was a risk of major bleeding.
13. Serious infections occurred within 4 weeks before the first administration,
including but not limited to complications requiring hospitalization, sepsis or
severe pneumonia.
14. Known to have active pulmonary tuberculosis (TB). Subjects suspected of active TB
should be examined by chest X-ray, sputum and excluded by clinical symptoms and
signs.
15. Untreated patients with chronic hepatitis B or chronic hepatitis B virus (HBV)
carriers with HBV DNA > 1000iu/ml, and patients with active hepatitis C should be
excluded. Inactive hepatitis B surface antigen (HBsAg) carriers, treated and stable
hepatitis B patients (HBV dna<1000iu/ml), and cured hepatitis C patients can be
enrolled. For HCV AB positive subjects, they are eligible to participate in the
study only if HCV RNA test results are negative.
16. Received the last radiotherapy or anti-tumor treatment (chemotherapy, targeted
therapy, Chinese herbal medicine used to control tumor disease or tumor
embolization, etc.) within 4 weeks before the first administration of candonilimab.
17. Major surgical procedures were performed within 30 days before the first dose of
candonilimab or had not yet fully recovered from previous surgery. Local surgery
(such as systemic port placement, core needle biopsy, and prostate biopsy) was
allowed, provided that the surgery was completed at least 24 hours before the first
administration of the study treatment drug.
18. Meningeal metastasis, spinal cord compression, leptomeningeal disease, or active
brain metastasis are known. However, subjects who meet the following requirements
and have measurable lesions outside the central nervous system are allowed to be
enrolled: 1) they have not been treated before and are currently asymptomatic (such
as no neurological dysfunction, epilepsy or other typical symptoms and signs of
central nervous system metastasis; no glucocorticoid treatment is required); 2)
After treatment, the patient was asymptomatic, and the imaging was stable for at
least 4 weeks before the start of study treatment (if there were no new or expanded
brain metastases), and the treatment of systemic glucocorticoids and anticonvulsants
had been stopped for at least 2 weeks.
19. According to the judgment of the investigator, subjects with pleural effusion,
pericardial effusion or ascites that cannot be stably controlled by repeated
drainage or other methods.
20. Uncontrolled concurrent diseases, including symptomatic congestive heart failure
(grade 3 or 4 according to the New York Heart Association functional
classification), uncontrolled hypertension, unstable angina, poorly controlled
arrhythmia, evidence of acute or ongoing myocardial ischemia, severe active peptic
ulcer disease or gastritis, Or mental illness / social condition that will restrict
subjects' compliance with research requirements or affect subjects' ability to
provide written informed consent. Any arterial thromboembolic event occurred within
6 months before enrollment, including myocardial infarction, cerebrovascular
accident or transient ischemic attack, with a history of deep vein thrombosis,
pulmonary embolism or any other serious thromboembolism.
21. the toxicity of previous anti-tumor treatment was not relieved, which was defined as
the toxicity did not return to grade 0 or 1 of NCI CTCAE version 5.0, or the level
specified in the inclusion / exclusion criteria, except for hair loss. Subjects who
have irreversible toxicity and are not expected to aggravate after the
administration of study drugs (such as hearing loss) may be included in the study
after consultation with the medical inspector. Subjects with long-term toxicity
caused by radiotherapy who cannot recover according to the judgment of the
investigator may be included in the study after consultation with the medical
inspector.
22. received a live vaccine within 30 days before the first dose of candonilimab or
planned to receive a live vaccine during the study period.
23. known history of severe hypersensitivity to other monoclonal antibodies.
24. are known to be allergic to any of the components of the candonilimab formulation.
25. pregnant or lactating women.
26. any condition that the investigator believes may lead to the risk of receiving study
drug treatment, or will interfere with the evaluation of study drug or the safety of
subjects or the analysis of study results.
Gender:
All
Minimum age:
18 Years
Maximum age:
70 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
The Second Affiliated Hospital, Zhejiang University School of Medicine
Address:
City:
Hangzhou
Country:
China
Status:
Recruiting
Contact:
Last name:
Ying Dong
Start date:
February 28, 2024
Completion date:
January 1, 2025
Lead sponsor:
Agency:
Second Affiliated Hospital, School of Medicine, Zhejiang University
Agency class:
Other
Source:
Second Affiliated Hospital, School of Medicine, Zhejiang University
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05926700
