About this trial

Cancer anorexia-cachexia syndrome is a common and severe complication in patients with advanced cancer, with a particularly high prevalence in pancreatic cancer. It is associated with systemic inflammation, metabolic disturbances, and dysregulation of central appetite control, leading to reduced quality of life, poor tolerance to anticancer therapy, and shortened survival. Anticancer treatments, including chemotherapy and immunotherapy, may further exacerbate the development and progression of cachexia.

Megestrol acetate is recommended as a first-line treatment for cancer-related anorexia-cachexia syndrome by multiple international and national guidelines, based on its proven effects on appetite stimulation, weight gain, and quality of life improvement. The nanocrystalline formulation of megestrol acetate significantly enhances bioavailability and achieves effective plasma concentrations even in the fasting state, making it particularly suitable for patients with cancer cachexia.

This randomized, controlled, prospective study aims to evaluate the efficacy and safety of nanocrystalline megestrol acetate in patients with advanced pancreatic cancer complicated by cancer anorexia-cachexia syndrome. The study will assess improvements in appetite, body weight, nutritional status, and quality of life, and explore the clinical value of early anti-cachexia intervention in the era of immuno-chemotherapy, providing evidence to optimize comprehensive treatment strategies for advanced pancreatic cancer.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Histologically or cytologically confirmed locally advanced or metastatic pancreatic ductal adenocarcinoma according to the TNM staging system of the International Association of Pancreatology and the 8th edition of the American Joint Committee on Cancer (AJCC);

No prior systemic antitumor therapy for recurrent or metastatic disease;

Prior adjuvant or neoadjuvant chemotherapy, radiotherapy, chemoradiotherapy, or immunotherapy for non-metastatic disease is allowed, provided that at least 6 months have elapsed since completion of the last treatment without disease recurrence;

At least one measurable lesion according to RECIST version 1.1 (previously irradiated lesions may be considered measurable only if there is clear evidence of disease progression after radiotherapy).

Disqualifiers

Active or untreated CNS metastases (e.g., brain or leptomeningeal metastases) as determined by CT or magnetic resonance imaging (MRI) during screening or based on prior imaging assessments. Patients with previously treated brain or leptomeningeal metastases may be eligible if the disease has been stable for ≥ 2 months and systemic corticosteroid therapy (>10 mg/day prednisone or equivalent) has been discontinued for > 4 weeks prior to randomization.

Uncontrolled tumor-related pain;

Women who are pregnant, breastfeeding, or planning to become pregnant during the study period;

Patients with a positive test result for human immunodeficiency virus (HIV);

Trial design

Design model

Parallel

Treatments tested in this trial

Nano-crystalline megestrol acetate
Drug
Nano-crystalline megestrol acetate is administered as an oral suspension at a dose of 625 mg once daily (5 mL, 125 mg/mL) starting concurrently with first-line chemotherapy and continued for up to 12 weeks. Unlike conventional megestrol acetate formulations, the nano-crystalline formulation utilizes reduced particle size to enhance oral bioavailability and improve weight gain outcomes. In this study, nano-crystalline megestrol acetate is used as an early supportive intervention in treatment-naïve patients with advanced pancreatic cancer-related anorexia-cachexia syndrome, rather than as salvage therapy. The intervention is delivered in combination with standard first-line chemotherapy regimens (AG, FOLFIRINOX, or NALIRIFOX). Administration of nano-crystalline megestrol acetate may be continued even if modifications, delays, or discontinuation of chemotherapy occur, in accordance with the study protocol. Safety and efficacy are prospectively monitored throughout treatment and follow-up.
First-line Chemotherapy
Drug
Participants in the control group will receive first-line chemotherapy alone, without nano-crystalline megestrol acetate. Chemotherapy regimens, including AG, FOLFIRINOX, or NALIRIFOX, will be selected and managed according to standard clinical practice.

Treatment groups

56 Participants

are divided into 2 treatment groups

Group A: Nano-crystalline Megestrol Acetate GroupExperimental treatment 2 interventions

Group B: Control GroupOther 1 intervention

Trial outcomes

Primary outcomes

1

Proportion of Patients Achieving >5% Weight Gain From Baseline(weight in kilograms,Kg)

The proportion of patients with advanced pancreatic cancer-related anorexia-cachexia syndrome who achieve a body weight increase of more than 5% compared with baseline(Kg) during first-line treatment combined with or without nano-crystalline megestrol acetate.

Time frame

12 weeks

Secondary outcomes

1

Change in Appetite Assessed by Functional Assessment of Anorexia/Cachexia Therapy-Anorexia/Cachexia Subscale (FAACT-A/CS 12)

Change from baseline in appetite as assessed by the Functional Assessment of Anorexia/Cachexia Therapy-Anorexia/Cachexia Subscale (FAACT-A/CS 12) in patients with advanced pancreatic cancer.The A/CS-12 Scale maintains the reliability, validity, and assessment accuracy of the FAACT questionnaire while reducing the number of items from 18 to 12. Each item is scored from 0 to 4, with a total score ranging from 0 to 48. Lower scores indicate poorer appetite in patients. When using the A/CS-12 Scale, it is recommended to use a total score ≤ 37 as the criterion for determining appetite loss in patients.

Time frame

12 weeks

2

Change in Body Composition Assessed by L3-CT

Change from baseline in body composition parameters, including skeletal muscle and adipose tissue area, assessed by computed tomography at the third lumbar vertebra (L3) level.A single cross-sectional image of the third lumbar vertebra (L3) is obtained via CT/MRI scanning. The skeletal muscles (psoas major, erector spinae, quadratus lumborum, transversus abdominis, external oblique, internal oblique) and adipose tissue in the L3 image are identified and quantified. Image analysis software such as Slice-O-Matic or Image J is used to calculate the total skeletal muscle area(skeletal muscle area in square centimeters,cm²) at this level. This area is then divided by the square of the patient's height(height in meters,m) to obtain the L3 Skeletal Muscle Index (L3-SMI,L3-SMI =skeletal muscle area (cm²) / (height(m))².Compare the changes in Skeletal Muscle Index (SMI) from baseline to the end of the study between the two groups (Megestrol Acetate group vs. control group).

Time frame

12 weeks

3

Change in Physical Function Scale

Change from baseline in physical function assessed using standardized functional assessment methods in patients with advanced pancreatic cancer.Physical Functioning Scale is assessed using a 4-point scale（from 1 to 4）, where a higher score on the functional scale indicates better function.

Time frame

12 weeks

4

Change in Quality of Life Assessed by European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30)

Change from baseline in health-related quality of life assessed by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30).The Overall Quality of Life Scale is divided into 7 levels, with scores ranging from 1 to 7. Higher scores indicate better overall quality of life.

Time frame

12 weeks

Other outcomes

1

Changes in C-reactive protein(mg/L)

Exploratory analysis of changes from baseline in inflammatory marker C-reactive protein(mg/L) between the experimental arm (first-line therapy combined with nanocrystalline megestrol acetate) and the control arm (first-line therapy alone) in the blood of patients with advanced pancreatic cancer.

Time frame

12 weeks

2

Changes in neutrophil-to-lymphocyte ratio

Exploratory analysis of changes from baseline in inflammatory marker neutrophil-to-lymphocyte ratio between the experimental arm (first-line therapy combined with nanocrystalline megestrol acetate) and the control arm (first-line therapy alone) in the blood of patients with advanced pancreatic cancer.

Time frame

12 weeks

3

Changes in cytokines (IL-1(pg/ml), IL-6(pg/ml), TNF-α(pg/ml))

Exploratory analysis of changes from baseline in cytokines (IL-1(pg/ml), IL-6(pg/ml) and TNF-α(pg/ml)) between the experimental arm (first-line therapy combined with nanocrystalline megestrol acetate) and the control arm (first-line therapy alone) in the blood of patients with advanced pancreatic cancer.

Time frame

12 weeks

4

Changes in nutritional biomarkers (albumin(g/L), prealbumin(g/L), hemoglobin(g/L))

Exploratory analysis of changes from baseline in nutritional biomarkers (albumin(g/L), prealbumin(g/L), hemoglobin(g/L)) between the experimental arm (first-line therapy combined with nanocrystalline megestrol acetate) and the control arm (first-line therapy alone) in the blood of patients with advanced pancreatic cancer.

Time frame

12 weeks

Nano-Megestrol Acetate for Cancer Cachexia in Advanced Pancreatic Cancer

About this trial

Eligibility criteria

Qualifiers

Disqualifiers

Trial design

Treatments tested in this trial

Treatment groups

Trial outcomes

Primary outcomes

Secondary outcomes

Other outcomes

Sponsors and contacts