Trial Title:
A Trial of Cadonilimab With Adriamycin in Patients With Advanced Soft Tissue Sarcoma
NCT ID:
NCT06367075
Condition:
Advanced Soft-tissue Sarcoma
Conditions: Official terms:
Sarcoma
Doxorubicin
Liposomal doxorubicin
Conditions: Keywords:
Advanced Soft-tissue Sarcoma
cadonilimab
chemotherapy
Anti-PD-1/CTLA4 bispecific antibody
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Not yet recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Intervention model description:
cadonilimab (AK104) with adriamycin
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Cadonilimab
Description:
injectable solution
Arm group label:
cadonilimab (AK104) with adriamycin
Other name:
AK104
Intervention type:
Drug
Intervention name:
Adriamycin
Description:
injectable solution
Arm group label:
cadonilimab (AK104) with adriamycin
Other name:
Doxorubicin
Summary:
This is a single-arm, multicenter trial of cadonilimab (AK104) with adriamycin in
patients with first-line advanced soft tissue sarcoma. the primary objective is to
evaluate objective response rate of cadonilimab with adriamycin.
Detailed description:
In this study, the screening period does not exceed 28 days, and subjects who are
qualified after completion of the screening examination and evaluation entered the
treatment period and undergo study treatment and visits as specified in the protocol. In
particular, tumor imaging assessments are performed every 2 cycles during the first 16
cycles; thereafter, tumor imaging assessments are performed every 4 cycles.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Patients who were pathologically confirmed soft tissue sarcoma (soft tissue sarcomas
other than alveolar/embryonal rhabdomyosarcoma, clear cell sarcoma, extraosseous
Ewing sarcoma, alveolar soft tissue sarcoma, well differentiated liposarcoma,
extraosseous myxoid chondrosarcoma, etc.)
- The patient was diagnosed as progressive and the investigators determined that the
lesion was not suitable for surgical treatment
- The patients had not received systemic therapy (including chemotherapy, targeted
therapy and bioimmunotherapy) for advanced soft tissue sarcoma. More than 6 months
have passed since the end of neoadjuvant/adjuvant therapy (including chemotherapy,
targeted therapy, bioimmunotherapy, etc.), and the cumulative dose of adriamycin
used in the past was ≤100 mg/m2
- In patients with measurable disease, lesions are defined and monitored by RECIST
v1.1
- Aged ≥ 18 years old, < 60 years old
- Eastern Cooperative Oncology Group (ECOG) performance status score of 0-1, amputees
can be 0-2
- Expected survival > 3 months
- Adequate organ and bone marrow function, defined as follows: ① Blood routine (14
days before screening without blood transfusion, without G-CSF, without drug
correction): neutrophil count (ANC) ≥ 1.5 × 10^9/L; platelet count (PLT) ≥ 100 ×
10^9/L; hemoglobin (Hb) ≥ 100 g/L; ② Blood biochemistry: serum creatinine (Cr) ≤ 1.5
× upper limit of normal (ULN) or creatinine clearance ≥ 60ml/min; total bilirubin
(TBIL) ≤ 1.5 × ULN; aspartate aminotransferase (AST) or alanine aminotransferase
(ALT) level ≤ 2.5 × ULN, The subjects with liver metastasis should be ≤ 5 × ULN; ③
Coagulation function: international normalized ratio (INR) ≤ 1.5, prothrombin time
(PT) and activated partial thromboplastin time (APTT) ≤ 1.5 × ULN; ④ Urinalysis:
urine protein < 2 +; if urine protein ≥ 2 +, the 24-hour urine protein
quantification must be ≤ 1g; ⑤ thyroid stimulating hormone (TSH) ≤ ULN and ≥ LLN; if
abnormal, T3 and T4 levels should be investigated, normal T3 and T4 levels can be
included
- Cardiac function:1) 12-lead electrocardiogram showed no severe arrhythmias, QTcF ≤
480 ms; 2) No signs of myocardial ischemia; 3) LVEF ≥55% by cardiac ultrasound
(measured by the biplane Simpson method); 4) NT-proBNP < age cutoff value; 5)
Troponin within normal values.
- Agree and have signed informed consent, willing and able to comply with scheduled
visits, study treatment, laboratory tests and other test procedures
- Women of childbearing potential should have a negative serum or urine pregnancy test
within 72 hours prior to receiving the first dose of study treatment; and should be
willing to use one acceptable contraception (i.e., oral contraceptives, condoms,
intrauterine devices [IUDs]) throughout the period of taking study treatment and for
at least 3 months after the last dose of study drug(s). For men, surgical
sterilization or consent to appropriate contraception during observation and up to
90 days after the last treatment should be used
Exclusion Criteria:
- known allergy to recombinant humanized anti-PD-1 monoclonal antibody drugs and their
components
- Known allergy to recombinant humanized anti-CTLA-4 monoclonal antibody drug and its
components
- known allergy to any component of the cadonilimab formulation
- Patients with cardiac disease class II or higher as determined by the New York Heart
Association (NYHA) score
- Palliative radiotherapy within 2 weeks prior to the first dose
- Other active malignancy within 5 years prior to enrollment. Except for locally
curable malignancies (manifested as cured) such as basal or cutaneous squamous cell
carcinoma, superficial bladder cancer, endometrial carcinoma in situ, cervical
carcinoma in situ, or breast carcinoma in situ
- Concurrent enrollment in another clinical study, unless it is an observational
(non-interventional) clinical study
- Active autoimmune disease requiring systemic therapy within 2 years prior to the
start of study treatment, or autoimmune disease that, in the judgment of the
Investigator, is likely to recur or for which treatment is planned; except for the
following: skin diseases not requiring systemic therapy (e.g., vitiligo, alopecia
areata, psoriasis, or eczema); hypothyroidism due to autoimmune thyroiditis
requiring only a stable dose of hormone replacement therapy; well-controlled type I
diabetes mellitus; childhood well-controlled type I diabetes mellitus; subjects
whose childhood asthma has completely resolved and does not require any intervention
in adulthood; and subjects who, in the judgment of the investigator, have a disease
that will not recur in the absence of external triggers
- Inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis, or chronic
diarrhea) that is active or requires clinical management
- Subjects will require systemic therapy with corticosteroids (>10 mg/day of
prednisone equivalents) or other immunosuppressive medications within 14 days of
administration of study drug. Inhaled or topical topical steroids and adrenal
replacement doses >10 mg/day of prednisone equivalent are allowed in the absence of
active autoimmune disease. Topical, ocular, intra-articular, intranasal and inhaled
corticosteroids (with minimal systemic absorption) are permitted in subjects.
Physiologic replacement doses of systemic corticosteroids are permitted, even if >10
mg/day of prednisone equivalent. Short-term use of corticosteroids is permitted for
prophylaxis (e.g., contrast allergy) or for treatment of non-autoimmune diseases
(e.g., delayed hypersensitivity reactions due to contact allergens)
- Known history of positive test for human immunodeficiency virus or known acquired
immunodeficiency syndrome
- History of known allogeneic organ transplantation and allogeneic hematopoietic stem
cell transplantation
- Known presence or history of interstitial lung disease
- Received a live vaccine within 30 days prior to the first dose of cadonilimab or
plan to receive a live vaccine during the study period
- Subjects with necrotic lesions detected on examination within 4 weeks prior to
enrollment that, in the judgment of the investigator, pose a risk of major bleeding
- Serious infection, including but not limited to concomitant complications requiring
hospitalization, sepsis, or severe pneumonia, within 4 weeks prior to first dose
- Known active tuberculosis (TB). Subjects suspected of having active TB will be
examined by chest X-ray, sputum, and exclusion by clinical signs and symptoms
- Patients with untreated chronic hepatitis B or chronic hepatitis B virus (HBV)
carriers with HBV DNA >1000 IU/mL, and patients with active hepatitis C should be
excluded. Inactive hepatitis B surface antigen (HbsAg) carriers, treated and
stabilized hepatitis B patients (HBV DNA <1000 IU/mL), and cured hepatitis C
patients may be enrolled. For HCV Ab-positive subjects, participation in the study
is eligible only if the HCV RNA test result is negative
- Major surgical procedure within 30 days prior to the first dose of cadonilimab or
have not fully recovered from a prior procedure. Localized surgical procedures
(e.g., systemic port placement, core needle biopsy, and prostate biopsy) are
permitted provided that the procedure is completed at least 24 hours prior to the
time of the first dose of study treatment medication
- Presence of known meningeal metastases, spinal cord compression, molluscum
contagiosum disease, or active brain metastases. However, enrollment is allowed for
subjects who meet the following requirements and have a measurable lesion outside
the CNS: 1) previously untreated and currently asymptomatic (e.g., no neurologic
deficits, seizures, or other signs and symptoms typical of CNS metastases;
glucocorticoid therapy is not required); 2) asymptomatic after treatment has been
imaging stable for at least 4 weeks prior to the initiation of study treatment
(e.g., no new or enlarging brain metastatic lesion ) and have discontinued systemic
glucocorticoid and anticonvulsant medication for at least 2 weeks
- Subjects with pleural effusions, pericardial effusions, or ascites that, in the
judgment of the Investigator, remain unstably controlled using repeated drainage or
other methods
- Uncontrolled co-morbidities, including symptomatic congestive heart failure (grade 3
or 4 as determined by the New York Heart Association functional classification),
uncontrolled hypertension, unstable angina, poorly controlled cardiac arrhythmias,
acute or evidence of ongoing myocardial ischemia, severe active peptic ulcer disease
or gastritis, or mental illness/social disease that would limit the subject's
ability to comply with the study requirements or interfere with the subject's
ability to provide written mental illness/social condition that would limit the
subject's ability to provide informed consent. Any arterial thromboembolic event,
including myocardial infarction, cerebrovascular accident, or transient ischemic
attack, history of deep vein thrombosis, pulmonary embolism, or any other serious
thromboembolism within 6 months prior to enrollment
- Unreversed toxicity from prior antineoplastic therapy, defined as toxicity that has
not returned to NCI CTCAE version 5.0 grade 0 or 1, or to a level specified in the
inclusion/exclusion criteria (except alopecia areata). Subjects who experience
irreversible toxicity that is not expected to worsen with administration of study
drug (e.g., hearing loss) may be included in the study after consultation with the
Medical Ombudsman. Subjects with radiotherapy-induced long-term toxicity that, in
the judgment of the Investigator, is not reversible may be included in the study
after consultation with the Medical Ombudsman
- Females who are pregnant or breastfeeding
- Any condition that, in the opinion of the Investigator, may render treatment with
the study drug risky or will interfere with the evaluation of the study drug or the
safety of the subject or the resolution of the study results
Gender:
All
Minimum age:
18 Years
Maximum age:
75 Years
Healthy volunteers:
No
Start date:
May 1, 2024
Completion date:
March 31, 2029
Lead sponsor:
Agency:
Wuhan Union Hospital, China
Agency class:
Other
Collaborator:
Agency:
Sun Yat-sen University
Agency class:
Other
Collaborator:
Agency:
Xiangya Hospital of Central South University
Agency class:
Other
Collaborator:
Agency:
Yunnan Cancer Hospital
Agency class:
Other
Collaborator:
Agency:
The Affiliated Hospital Of Guizhou Medical University
Agency class:
Other
Collaborator:
Agency:
First Affiliated Hospital of Guangxi Medical University
Agency class:
Other
Source:
Wuhan Union Hospital, China
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06367075
