A Clinical Study of Nanocrystalline Megestrol Acetate in Concurrent Chemoradiotherapy for Locally Advanced Cervical Cancer

Eligibility Criteria:

• Voluntarily sign the written ICF.
• Age ≥ 18 years at the time of enrollment.
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0-2.
• Expected survival period ≥ 6 months.
• Histologically or cytologically confirmed locally advanced cervical cancer (Stage IB3/IIA2/IIB-IVA) that is not amenable to complete surgical resection, classified according to the International Federation of Gynecology and Obstetrics (FIGO) staging system.
• Scheduled to undergo radical concurrent chemoradiotherapy.
• At least one measurable tumor lesion according to RECIST v1.1.
• Adequate organ function defined as follows:

a) Hematology (without any blood component or growth factor support within 7 days prior to initiation of study treatment): i. Absolute neutrophil count (ANC) ≥ 1.5 × 10⁹/L (1,500/mm³); ii. Platelet count ≥ 100 × 10⁹/L (100,000/mm³); iii. Hemoglobin ≥ 90 g/L. b) Renal: i. Calculated creatinine clearance* (CrCl) ≥ 50 mL/min

• CrCl will be calculated using the Cockcroft-Gault formula:

CrCl (mL/min) = (140 - age) × weight (kg) × F / (serum creatinine [mg/dL] × 72) F = 1 for males; F = 0.85 for females ii. Urine protein ≤ 1+ or 24-hour urinary protein quantification < 1.0 g. c) Hepatic: i. Total bilirubin (TBil) ≤ 1.5 × ULN; for patients with liver metastases or confirmed/suspected Gilbert's disease, TBil ≤ 3 × ULN; ii. AST and ALT ≤ 2.5 × ULN; for patients with liver metastases, AST and ALT ≤ 5 × ULN; iii. Serum albumin (ALB) ≥ 28 g/L. d) Coagulation: i. International normalized ratio (INR) and activated partial thromboplastin time (APTT) ≤ 1.5 × ULN (unless the patient is receiving anticoagulant therapy and coagulation parameters [PT/INR and APTT] are within the therapeutic range at screening).

e) Cardiac: i. Left ventricular ejection fraction (LVEF) ≥ 50%.

• Female patients of childbearing potential must have a negative urine or serum pregnancy test within 3 days prior to the first dose (if urine pregnancy test result is not confirmed negative, a serum pregnancy test will be required, and the serum result shall prevail). If a female patient of childbearing potential engages in sexual activity with a non-sterilized male partner, she must use acceptable contraceptive methods starting from screening and continue for 120 days after the last dose of study drug; whether to discontinue contraception after this time point should be discussed with the investigator. If a non-sterilized male patient engages in sexual activity with a female partner of childbearing potential, he must use effective contraceptive methods from screening until 120 days after the last dose; whether to discontinue contraception after this time point should be discussed with the investigator.
• The patient is willing and able to comply with scheduled visits, treatment plans, laboratory tests, and other study requirements.

Exclusion criteria

Patients meeting any of the following criteria will be ineligible for this study:

• Conditions affecting gastrointestinal absorption such as dysphagia, malabsorption, or uncontrolled vomiting; ongoing tube feeding or parenteral nutrition; presence of anorexia nervosa, psychogenic anorexia, or pain-induced feeding difficulties.
• Current or planned use of medications that increase appetite or weight, including but not limited to: adrenal corticosteroids (except short-term dexamethasone during chemotherapy), androgens, progestins, thalidomide, olanzapine, anamorelin, or other appetite stimulants.
• Diagnosis of Cushing's syndrome, adrenal or pituitary insufficiency; poorly controlled diabetes mellitus.
• Current radiographic or clinical evidence of gastrointestinal obstruction.
• Active autoimmune disease requiring systemic treatment within the past two years (e.g., disease-modifying agents, corticosteroids, immunosuppressants). History of non-infectious pneumonitis/interstitial lung disease requiring systemic glucocorticoid therapy, or current non-infectious pneumonitis.
• Uncontrolled concurrent illnesses including but not limited to decompensated cirrhosis, renal failure, uncontrolled metabolic disorders, severe active peptic ulcer disease/gastritis, or psychiatric/social conditions that would limit compliance with study requirements or the ability to provide written informed consent.
• Within 12 months prior to the first dose: unstable angina requiring hospitalization, myocardial infarction, congestive heart failure (NYHA Class II or higher), vascular disease (e.g., aortic aneurysm at risk of rupture), or other cardiac impairments that may affect safety evaluation of the study drug (e.g., poorly controlled arrhythmia, myocardial ischemia). Within 6 months prior to the first dose: history of esophagogastric varices, severe ulcers, gastrointestinal perforation and/or fistula, gastrointestinal obstruction (including incomplete intestinal obstruction requiring parenteral nutrition), intra-abdominal abscess, or acute gastrointestinal bleeding.
• Within 6 months prior to the first dose: any arterial thromboembolic events, Grade 3 or higher venous thromboembolism per NCI CTCAE v5.0 requiring urgent intervention (e.g., pulmonary embolism or intracardiac thrombosis), transient ischemic attack, cerebrovascular accident, hypertensive crisis, or hypertensive encephalopathy. Within 1 month prior to the first dose: acute exacerbation of chronic obstructive pulmonary disease. Current hypertension with systolic BP ≥160 mmHg or diastolic BP ≥100 mmHg despite oral antihypertensive therapy.
• History of severe bleeding tendency or coagulopathy; clinically significant bleeding symptoms within 1 month prior to the first dose, including but not limited to gastrointestinal bleeding, hemoptysis (defined as coughing/expectorating ≥1 teaspoon of fresh blood or small clots, or blood without sputum; patients with blood-tinged sputum are eligible), epistaxis (excluding minor nasal bleeding and blood-tinged postnasal drip).
• Within 4 weeks prior to the first dose: severe infections including but not limited to complications requiring hospitalization, sepsis, or severe pneumonia; within 2 weeks prior to the first dose: active infection requiring systemic antimicrobial therapy (excluding antiviral therapy for hepatitis B/C).
• Any condition, treatment, or laboratory abnormality that may confound study results, impede complete study participation, or make participation not in the patient's best interest.