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

Browse trials for

• Carcinoma, Hepatocellular 3,174
• Cachexia 327
• Anorexia 412
• Malnutrition 1,585

Study arms

• Placebo comparator
  Placebo group

  Drug: Placebo

• Experimental
  Nanocrystalline megestrol acetate

  Drug: Nanocrystalline megestrol acetate

Interventions

• DrugNanocrystalline megestrol acetate

  The dose of medroxyprogesterone used in this study was 625 mg/day. The first systemic treatment administration was defined as baseline, with continuous use of nanocrystalline medroxyprogesterone or placebo for 12 weeks during the antitumor therapy period.

• DrugPlacebo

  The first systemic treatment administration was defined as baseline, with continuous use of nanocrystalline medroxyprogesterone or placebo for 12 weeks during the antitumor therapy period.

Primary outcomes

1. 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

1. 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).

2. 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.

3. Objective Response Rate

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

4. 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).

5. 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.

6. 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).

7. 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).

8. 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.

9. 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).

10. Nutritional indicators

    Albumin (ALB),Hemoglobin (Hb)

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

Individual participant data

Plan to share: Yes