Using cadonilimab with chemotherapy and radiation for advanced endometrial cancer

A Phase II, Single-arm, Multicenter Clinical Trial of Definitive Treatment With Cadonilimab, Paclitaxel, Cisplatin and Radiation for the Treatment of Locally Recurrent and Oligometastatic Endometrial Carcinoma

This study is testing if adding cadonilimab to chemotherapy and radiation can help people with advanced endometrial cancer live longer and feel better.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 30 (estimated)
• Ages: 18 Years to 80 Years
• Sex: Female
• Sponsor: Shandong Cancer Hospital and Institute (Academic / other)
• Drugs / interventions: chemotherapy, immunotherapy, radiation, prednisone, cadonilimab
• Locations: 1 site (Jinan, Shandong)
• Trial ID: NCT06532539 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the effectiveness and safety of cadonilimab combined with paclitaxel, cisplatin, and radiation therapy in patients with locally recurrent and oligometastatic endometrial carcinoma. The study aims to determine if this combination improves overall response rates, progression-free survival, disease control rates, and overall survival while also identifying predictive biomarkers for treatment efficacy. Participants will receive the treatment according to a specified protocol and will be monitored closely for various health outcomes. Additionally, they will provide samples for biomarker exploration to enhance future treatment strategies.

Who should consider this trial

Good fit: Ideal candidates include females aged 18 to 80 with locally recurrent or oligometastatic endometrial cancer after initial treatment.

Not a fit: Patients with more than five recurrent or metastatic lesions or those with other types of cancer may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could significantly improve treatment outcomes for patients with advanced endometrial cancer.

How similar studies have performed: While this specific combination is novel, similar immunotherapy approaches have shown promise in treating various cancers.

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.

Where this trial is running

Jinan, Shandong

• Shandong Cancer Hospital Affiliated to Shandong First Medical University — Jinan, Shandong, China (Recruiting)

Study contacts

• Principal investigator: Peng Xie — Shandong Cancer Hospital and Institute
• Study coordinator: Jing Liu

Conditions Endometrial Neoplasms; Neoplasm Recurrence, Local; Neoplasm Metastasis; Immunotherapy; Cadonilimab; Paclitaxel; Cisplatin; Radiation Therapy