Trial Title:
Cadonilimab With Chemoradiation for Recurrent and Oligometastatic Endometrial Carcinoma
NCT ID:
NCT06532539
Condition:
Endometrial Neoplasms
Neoplasm Recurrence, Local
Neoplasm Metastasis
Conditions: Official terms:
Neoplasms
Neoplasm Metastasis
Endometrial Neoplasms
Neoplasm Recurrence, Local
Recurrence
Paclitaxel
Cisplatin
Conditions: Keywords:
Immunotherapy
Cadonilimab
Paclitaxel
Cisplatin
Radiation Therapy
Combined Modality Therapy
Clinical Trials, Phase II as Topic
Progression-Free Survival
Biomarkers, Tumor
Treatment Outcome
Safety
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:
Paclitaxel and Cisplatin
Description:
Paclitaxel and Cisplatin Paclitaxel: 135 mg/m², intravenous infusion, Day 1, every 3
weeks (Q3W). Cisplatin: 75 mg/m², intravenous infusion, Days 1-3, every 3 weeks (Q3W).
Duration: 6-8 cycles, until disease progression or intolerable adverse effects as judged
by the investigator.
Alternative: If contraindicated for cisplatin, or if there is an allergy to paclitaxel
and/or cisplatin, alternative drugs such as different types of paclitaxel or carboplatin
can be used.
Arm group label:
Treatment Arm
Other name:
TP
Intervention type:
Drug
Intervention name:
Cadonilimab
Description:
Cadonilimab: 5-10 mg/kg, intravenous infusion, Day 1, every 3 weeks (Q3W). Duration:
Continuous administration until disease progression, death, intolerable toxicity,
subject's voluntary withdrawal, investigator's decision for withdrawal, or a maximum of
24 months.
Arm group label:
Treatment Arm
Other name:
AK104
Intervention type:
Radiation
Intervention name:
Radiotherapy
Description:
Site Selection: Original site, lymph nodes, lung metastasis, bone metastasis, adrenal
metastasis, brain metastasis, and other relatively isolated, well-vascularized lesions.
Select at least one suitable lesion for radiotherapy based on the impact of the recurrent
or metastatic lesion on the body, prioritizing lesions that cause symptoms, are
life-threatening, or are expected to cause symptoms.All tumor lesions will be irradiated,
which can be done in phases.
Dosage and Fractionation: Conventional or hypofractionated radiotherapy, with a
biologically effective dose (BED) of ≥ 72 Gy. Dose adjustments can be made for brain
metastases.
Timing: After completing relevant baseline examinations, radiotherapy can be implemented
generally after 2-6 cycles of systemic therapy, or after the first cycle for small,
solitary metastatic lesions.
echnique: IMRT, TOMO, SBRT, 3D-BT, interstitial implantation therapy, or proton therapy.
Arm group label:
Treatment Arm
Summary:
The goal of this clinical trial is to evaluate the efficacy and safety of cadonilimab in
combination with paclitaxel, cisplatin, and radiation therapy for the treatment of
locally recurrent and oligometastatic endometrial carcinoma. The main questions it aims
to answer are:
1. Does the combination therapy improve the overall response rate (ORR),
progression-free survival (PFS), disease control rate (DCR), overall survival (OS),
and safety in participants?
2. What are the predictive biomarkers of treatment efficacy, and how can this
information better guide the use of immune-oncology drugs in combination therapy?
Participants will:
- Receive cadonilimab, paclitaxel, cisplatin, and radiation therapy according to a
specified protocol.
- Visit the clinic for regular checkups and tests throughout the treatment period.
- Be monitored for and have records kept of ORR, PFS, DCR, OS, and safety.
- Provide hematologic and tissue samples to explore biomarkers.
This study will help determine if this combination therapy can become a new standard of
care for patients with locally recurrent and oligometastatic endometrial carcinoma, as
well as identify biomarkers to better guide treatment strategies.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. A written informed consent form must be signed before the implementation of any
trial-related procedures.
2. Female, aged 18 years or older and 80 years or younger.
3. ECOG PS 0-1.
4. Newly diagnosed with histologically or cytologically confirmed primary endometrioid
adenocarcinoma, serous carcinoma, clear cell adenocarcinoma, undifferentiated
carcinoma, mixed cell adenocarcinoma, mesonephric adenocarcinoma, mucinous
carcinoma, intestinal-type mesonephric-like adenocarcinoma, and carcinosarcoma,
meeting the clinical diagnostic criteria for endometrial cancer.
5. Patients with locally recurrent or oligometastatic endometrial cancer after initial
treatment. The number of recurrent and metastatic lesions is ≤5. Screening criteria
for oligometastasis: lymph node metastases in the same region count as one
metastatic lesion; liver metastases are limited to one; lung metastases are limited
to three.
6. At least one site suitable for radiotherapy (including the primary lesion),
measurable, and meeting the RECIST v1.1 criteria for evaluable lesions.
7. Tumor samples available for biomarker assessment.
8. Expected survival time ≥6 months.
9. Normal major organ function (within 7 days before enrollment), meeting the following
criteria:
(1) Hematology standards (without blood transfusion or hematopoietic growth factor
treatment within 14 days before enrollment):
1. Hemoglobin (HB) ≥80 g/L;
2. Absolute neutrophil count (ANC) ≥1.5×10^9/L;
3. Platelet count (PLT) ≥50×10^9/L; (2) No functional or organic diseases, meeting the
following criteria:
a) Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5×ULN, total
serum bilirubin ≤1.5×ULN, alkaline phosphatase (ALP) ≤3×ULN, serum albumin ≥30 g/L; b)
Serum creatinine (Cr) ≤1.5×ULN; if serum creatinine is >1.5×ULN, creatinine clearance
(CrCl) ≥50 mL/min (calculated using the Cockcroft-Gault formula); c) Prothrombin time
(PT) prolongation ≤6 seconds, activated partial thromboplastin time (APTT) ≤1.5×ULN; d)
Thyroid-stimulating hormone (TSH) ≤ULN (if abnormal, FT3 and FT4 levels should be
considered; if FT3 and FT4 levels are normal, enrollment is allowed); f) Left ventricular
ejection fraction (LVEF) >50%. 11. Before starting the first treatment, all reversible
toxic reactions from previous anti-tumor treatments must have resolved to ≤ grade 1
(based on CTCAE v5.0), excluding any grade of alopecia and pigmentation, ≤ grade 2
peripheral sensory neuropathy, and other abnormalities considered by the investigator
and/or sponsor to pose a benefit-risk balance favoring the subject receiving the study
treatment.
12. Non-surgically sterilized or childbearing potential female patients must use
medically recognized contraception (e.g., intrauterine device, contraceptive pill,
or condom) during the study treatment period and for 3 months after the end of the
study treatment. Non-surgically sterilized childbearing potential female patients
must have a negative serum or urine HCG test within 7 days before enrollment and
must not be breastfeeding.
Exclusion Criteria:
1. Subjects with any active autoimmune disease or history of autoimmune disease (e.g.,
but not limited to: autoimmune hepatitis, interstitial lung disease, uveitis,
enteritis, hepatitis, hypophysitis, vasculitis, nephritis, hyperthyroidism,
hypothyroidism; subjects with vitiligo or childhood asthma that has completely
resolved and does not require any intervention in adulthood may be included;
subjects with asthma requiring medical intervention with bronchodilators are not
eligible).
2. Subjects currently using immunosuppressive agents or systemic, or absorbable local
corticosteroid therapy to achieve immunosuppressive purposes (dose >10 mg/day
prednisone or equivalent) and continuing use within 2 weeks prior to enrollment.
3. Known history of grade 3 or 4 immune-related adverse events associated with previous
anti-tumor immunotherapy.
4. Poorly controlled cardiac clinical symptoms or diseases, such as: (1) NYHA class II
or higher heart failure; (2) unstable angina; (3) myocardial infarction within the
past six months; (4) clinically significant supraventricular or ventricular
arrhythmias requiring treatment or intervention; (5) QTc >450 ms (males); QTc >470
ms (females).
5. Coagulation dysfunction (INR >1.5 or PT >16 s), bleeding tendency, or receiving
thrombolytic or anticoagulant therapy.
6. Subjects who have received radiotherapy, chemotherapy, hormone therapy, surgery, or
molecular targeted therapy within 4 weeks (or 5 drug half-lives, whichever is
longer) prior to the first dose of the study drug; subjects with adverse events from
previous treatments (excluding alopecia) that have not recovered to ≤CTCAE grade 1.
7. Subjects with clinically uncontrolled third-space effusion requiring puncture
drainage or other local treatment prior to the first dose of the investigational
drug.
8. Subjects with significant hemoptysis within 2 months before randomization, or
hemoptysis of at least half a teaspoon (2.5 ml) per day.
9. Known hereditary or acquired bleeding and thrombotic tendencies (e.g., hemophilia,
coagulation dysfunction, thrombocytopenia, hypersplenism).
10. Subjects with active infection or unexplained fever >38.5°C during the screening
period or prior to the first dose.
11. Subjects with a history of or current evidence of lung fibrosis, interstitial lung
disease, pneumoconiosis, radiation pneumonitis, drug-related pneumonitis, or
severely impaired lung function.
12. Subjects with congenital or acquired immune deficiencies (e.g., HIV infection) or
active hepatitis (hepatitis B reference: HBV DNA exceeding the upper limit of
normal; hepatitis C reference: HCV viral load or RNA exceeding the upper limit of
normal).
13. Subjects who have used other investigational drugs or similar therapeutic agents
within 4 weeks prior to the first dose or who have received radiotherapy or other
local treatments within 2 weeks prior to the first dose and have not recovered from
the adverse effects of such treatments.
14. Subjects with a history of or concurrent other malignancies (excluding cured basal
cell carcinoma of the skin and cervical carcinoma in situ).
15. Subjects who may receive other systemic anti-tumor therapies during the study
period.
16. Subjects who have received or are expected to receive live vaccines within 4 weeks
prior to the first dose or during the study period.
17. Subjects with other factors that may lead to forced termination of the study as
judged by the investigator, such as severe diseases (including mental disorders)
requiring combined treatment, severe laboratory abnormalities, and family or social
factors that may affect the safety of the subject or the collection of data and
samples.
Gender:
Female
Minimum age:
18 Years
Maximum age:
80 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Shandong Cancer Hospital Affiliated to Shandong First Medical University
Address:
City:
Jinan
Country:
China
Status:
Recruiting
Contact:
Last name:
Jing Liu
Start date:
June 13, 2024
Completion date:
May 2026
Lead sponsor:
Agency:
Shandong Cancer Hospital and Institute
Agency class:
Other
Source:
Shandong Cancer Hospital and Institute
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06532539
