Nanocrystalline Megestrol Acetate Versus Placebo for Anorexia in Patients With Unresectable Hepatocellular Carcinoma Receiving TACE Combined With Targeted and Immunotherapy

Phase 2Not Yet RecruitingNCT07565415

Nanfang Hospital, Southern Medical University88 enrolled

Overview

Primary Objective: To evaluate the effect of nanocrystalline megestrol acetate versus placebo on body weight and appetite in patients with unresectable hepatocellular carcinoma receiving TACE combined with targeted and immunotherapy.Secondary Objectives: To evaluate the effect of nanocrystalline megestrol acetate versus placebo on quality of life, inflammatory markers, nutritional indicators, and psychological stress in patients with unresectable hepatocellular carcinoma receiving TACE combined with targeted and immunotherapy.Exploratory Objective: To explore the impact of nanocrystalline megestrol acetate versus placebo on survival benefit in patients with unresectable hepatocellular carcinoma receiving TACE combined with targeted and immunotherapy.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

Conditions

Hepatocellular Carcinoma (HCC)Cachexia Anorexia Malnutrition

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Patients with unresectable primary hepatocellular carcinoma (HCC) confirmed by imaging or histopathology * No previous receipt of immunotherapy and/or targeted drug therapy * Child-Pugh score ≤ 7 * At least one measurable lesion per RECIST 1.1 criteria; lesions without prior radiotherapy, cryotherapy or other local treatment * Single intrahepatic lesion \< 10 cm, or fewer than 10 intrahepatic lesions with tumor burden \< 50% * Meet precachexia criteria: non-volitional weight loss ≤ 5% in 6 months, plus systemic inflammation (CRP \> 5 mg/L) or decreased appetite (FAACT-A/CS-12 score ≤ 37 points) * Meet cachexia criteria: accompanied by decreased appetite or systemic inflammation, with either non-volitional weight loss \> 5% in 6 months or BMI \< 18.5 kg/m² plus weight loss \> 2% * Voluntarily participate and sign informed consent * Age ≥ 18 years, male or female * Able to swallow tablets normally * ECOG performance status 0 or 1 * Life expectancy ≥ 12 weeks * Adequate major organ function without blood products or colony-stimulating factors within 14 days * Hematology: ANC ≥ 1.5×10⁹/L, Hb ≥ 80 g/L, PLT ≥ 50×10⁹/L * Liver function: TBIL ≤ 1.5×ULN, AST/ALT ≤ 5.0×ULN, ALB ≥ 28 g/L * Coagulation function: INR, PT or aPTT ≤ 1.5×ULN * Renal function: SCr ≤ 1.5×ULN or creatinine clearance ≥ 60 mL/min * Urine protein ≤ 1+ or 24-hour urine protein \< 1.0 g * Cardiac function: LVEF ≥ 50% * Females of childbearing potential with negative pregnancy test within 3 days before first dosing * Fertile male and female patients agree to effective contraception from screening to 120 days after last study drug * HBV/HCV infected patients receive stable antiviral therapy without drug interaction Exclusion Criteria: * Active or untreated CNS metastases; inadequately controlled metastatic brain or leptomeningeal disease * Uncontrolled tumor-related pain * Thromboembolic disease, ascites or lower limb edema within 6 months * History of other malignancies within 5 years before randomization, except curable low-risk tumors * Unresolved adverse toxicities from prior antitumor therapy not recovered to ≤ Grade 1 (CTCAE v5.0), excluding alopecia * Pregnant, breastfeeding females or those planning pregnancy during the study * Any unstable medical, psychiatric or social condition that may interfere with study participation * Positive HIV infection * Major surgery within 28 days prior to randomization * Severe cardiovascular disease, myocardial infarction, unstable arrhythmia, angina or cerebrovascular events * Severe systemic infection within 4 weeks before dosing or active infection requiring systemic anti-infective treatment * Impaired gastrointestinal absorption, long-term tube feeding, parenteral nutrition or eating disorders * Concomitant use of other appetite-enhancing or weight-stimulating agents * Cushing's syndrome, adrenal or pituitary insufficiency, poorly controlled diabetes * Uncontrolled hypertension despite oral antihypertensive treatment * Esophagogastric varices, severe ulcers, gastrointestinal bleeding, obstruction, perforation or fistula within 6 months * Known hypersensitivity to any component of the investigational product * Any other condition considered inappropriate for enrollment by the investigator.

Outcomes

Primary Outcomes

The proportion of patients with >5% weight loss from baseline.

Weight is measured in kilograms (kg).

Time frame: Percentage weight change at Week 12 compared to baseline

Secondary Outcomes

L3-SMI

A single cross-sectional image of the third lumbar vertebra (L3) is obtained via CT/MRI scanning. Skeletal muscles at the L3 level, including the psoas major, erector spinae, quadratus lumborum, transversus abdominis, external oblique, and internal oblique muscles, are identified and quantified. The total skeletal muscle area of this slice is calculated using image analysis software such as Slice-O-Matic or ImageJ. The L3 skeletal muscle index (L3-SMI) is then derived by dividing the total muscle area by the square of height.

Time frame: Baseline(day1); prior to dosing in each systemic treatment cycle(each cycle lasts 21-28 days).

The incidence and severity of adverse events (AEs) assessed by CTCAE5.0

Time frame: Adverse events (AEs) of each subject will be followed up for 30 days after the last dose of nanocrystalline megestrol acetate or until the initiation of new anti-tumor therapy, whichever occurs first.

Objective Response Rate

Time frame: Baseline(day1), and after every two treatment cycles(up to 2 years).each cycle lasts 21-28 days.

Life quality

The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) contains 30 items to evaluate health-related quality of life in cancer patients. The global quality of life scale is scored from 1 to 7. All other items use a 4-point scale (1 = not at all, 2 = a little, 3 = quite a bit, 4 = very much). The raw score of each domain is the average score of its corresponding items. All raw scores are linearly converted to standardized scores ranging from 0 to 100 for unified comparison.For functional scales, the standardized score is calculated as: \[1 - (RS-1)/range\] × 100. The range refers to the score interval of each domain, namely the difference between the maximum and minimum values. Higher scores in functional domains and the global quality of life scale represent better function and quality of life. Higher scores on symptom scales and single-item measurements reflect more severe symptoms or health-related problems.

Time frame: Baseline(day1); prior to dosing in each systemic treatment cycle(each cycle lasts 21-28 days).

Overall Survival

Overall survival was defined as the time from randomization to death from any cause.

Time frame: Baseline(day 1); prior to dosing in each systemic treatment cycle(up to 2 years,each cycle is 21-28 days), assessed up to 100 weeks.

Inflammatory markers

CRP：C-reactive protein IL-6：Interleukin-6 IL-1：Interleukin-1

Time frame: Baseline(day1); prior to dosing in each systemic treatment cycle(each cycle is 21-28 days).

Anxiety and depression

Anxiety and depression were assessed using the following two scales respectively. Depressive symptoms were assessed using the Patient Health Questionnaire-9 (PHQ-9). Developed based on DSM-IV depression criteria, this 9-item scale evaluates depressive symptoms over the past two weeks. Each item is scored 0-3 points, with a total score ranging from 0 to 27. Higher total scores indicate more severe depressive symptoms. A score of ≥1 on Item 9 suggests suicidal risk. The PHQ-9 is used only for screening, not formal depression diagnosis. Anxiety symptoms were assessed using the Generalized Anxiety Disorder 7-item scale (GAD-7). This 7-item international scale evaluates anxiety conditions in the previous two weeks. Each item adopts a 4-point scoring method, with a total score of 0-21. Higher scores correspond to increased anxiety severity.

Time frame: Baseline(day1); prior to dosing in each systemic treatment cycle(each cycle lasts 21-28 days).

Progression-Free Survival

Progression-free survival was defined as the time from randomization to tumor progression or death, whichever occurred first.

Time frame: Baseline(day1); prior to dosing in each systemic treatment cycle(each cycle lasts 21-28 days)with a maximum follow-up of 100 weeks.

Appetite status assessment

The A/CS-12 is a subscale of the Functional Assessment of Anorexia/Cachexia Therapy (FAACT). It enables quantitative and qualitative assessment of anorexia. Each item is scored from 0 to 4 points, with a total score ranging from 0 to 48. Lower scores indicate poorer appetite status.

Time frame: Baseline(day1); prior to dosing in each systemic treatment cycle(each cycle is 21-28 days).

Nutritional indicators

Albumin (ALB),Hemoglobin (Hb)

Time frame: Baseline(day1); prior to dosing in each systemic treatment cycle(each cycle is 21-28 days).

Nanocrystalline Megestrol Acetate Versus Placebo for Anorexia in Patients With Unresectable Hepatocellular Carcinoma Receiving TACE Combined With Targeted and Immunotherapy

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts