Nano-Megestrol Acetate for Cancer Cachexia in Advanced Pancreatic Cancer

NCT07408505 | Recruiting

• 1 other identifier: SDZLEC2025-481-02
• Study Type: interventional
• Target: 56
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Advanced Pancreatic Ductal Adenocarcinoma; Cancer Anorexia-Cachexia Syndrome

Keywords

Pancreatic ductal adenocarcinoma; Cancer anorexia-cachexia syndrome; Nanocrystalline megestrol acetate; Body weight and body composition; Appetite improvement

Outcome Measures

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.

  12 weeks

Secondary Outcomes (10)

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

  12 weeks

• Change in Body Composition Assessed by L3-CT

  12 weeks

• Change in Physical Function Scale

  12 weeks

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

  12 weeks

• Incidence and Severity of Adverse Events

  12 weeks

Other Outcomes (4)

• Changes in C-reactive protein(mg/L)

  12 weeks

• Changes in neutrophil-to-lymphocyte ratio

  12 weeks

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

  12 weeks

Study Arms (2)

Nano-crystalline Megestrol Acetate Group

EXPERIMENTAL

Participants assigned to the experimental arm will receive nano-crystalline megestrol acetate oral suspension in combination with first-line chemotherapy. Nano-crystalline megestrol acetate will be administered orally at a dose of 625 mg once daily (5 mL, 125 mg/mL), starting on the first day of chemotherapy and continued for up to 12 weeks. First-line chemotherapy will be selected by the investigator according to clinical guidelines and practice, including AG, FOLFIRINOX, or NALIRIFOX regimens. If the primary antitumor treatment is modified, delayed, or discontinued during the study, nano-crystalline megestrol acetate may be continued until completion of the 12-week treatment period. Patients will be followed for efficacy and safety assessments according to the study protocol.

Drug: Nano-crystalline megestrol acetate; Drug: First-line Chemotherapy

Control Group

OTHER

Participants assigned to the control group will receive first-line chemotherapy alone, without nano-crystalline megestrol acetate. First-line chemotherapy will be selected by the investigator according to clinical guidelines and standard clinical practice, including AG, FOLFIRINOX, or NALIRIFOX regimens. Chemotherapy dosing, schedule, and modifications will be managed according to routine clinical practice and institutional standards. Participants will be followed for efficacy and safety assessments according to the study protocol.

Drug: First-line Chemotherapy

Interventions

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.

Control Group; Nano-crystalline Megestrol Acetate Group

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.

Nano-crystalline Megestrol Acetate Group

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must meet all of the following criteria to be eligible for enrollment:
• 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).
• \. Fulfillment of Fearon criteria for cachexia or pre-cachexia:
• (1) Cachexia stage according to Fearon criteria: fulfillment of any of the following criteria in combination with decreased appetite (FAACT-A/CS 12 score ≤ 37) or systemic inflammation (CRP \> 5 mg/L):
• ① Unintentional weight loss \> 5% within the past 6 months;
• Body weight loss \> 2% in patients with a BMI \< 18.5 kg/m². (2) Pre-cachexia stage according to Fearon criteria: all of the following three conditions must be met:
• ① Unintentional weight loss ≤ 5% within the past 6 months;
• Systemic inflammation (CRP \> 5 mg/L);
• Good compliance and provision of written informed consent;
• Age 18-75 years, regardless of sex;
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2;
• Expected survival greater than 4 months;

You may not qualify if:

• Patients meeting any of the following criteria will be excluded from this study:
• 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 hepatitis B or hepatitis C:
• ① Patients with a history of hepatitis B virus (HBV) infection must undergo HBV deoxyribonucleic acid (DNA) testing; only patients with negative HBV DNA (HBV DNA \< 1000 copies/mL or \< 200 IU/mL or below the upper limit of normal) are eligible for participation in this study;
• ② Among patients who are positive for hepatitis C virus (HCV) antibodies, only those with negative HCV ribonucleic acid (RNA) by polymerase chain reaction (PCR) testing are eligible to participate in this study;
• Patients with a positive test result for human immunodeficiency virus (HIV);
• Major surgery (excluding diagnostic procedures) within 28 days prior to randomization, or anticipated major surgery during the study period;
• Significant cardiovascular disease, such as heart disease defined as New York Heart Association class II or higher, myocardial infarction within 3 months prior to randomization, unstable arrhythmia, unstable angina, cerebrovascular accident, or transient ischemic attack. Patients with known coronary artery disease, congestive heart failure not meeting the above criteria, or left ventricular ejection fraction \< 50% must be receiving optimal stable therapy as determined by the treating physician; consultation with a cardiologist may be obtained if necessary;
• Severe infection occurring within 4 weeks prior to first dosing, including but not limited to infections with complications requiring hospitalization, sepsis, or severe pneumonia; or active infection requiring systemic anti-infective therapy within 2 weeks prior to first dosing (excluding antiviral therapy for hepatitis B or C).
• Conditions affecting gastrointestinal absorption, including dysphagia, malabsorption, or uncontrolled vomiting; difficulty in food intake or requirement for tube feeding or parenteral nutrition; anorexia nervosa; anorexia caused by psychiatric disorders or pain-related inability to eat;
• Current or planned use of other medications that increase appetite or body weight, such as corticosteroids (except short-term dexamethasone use during chemotherapy), androgens, progestins, thalidomide, olanzapine, anamorelin, or other appetite stimulants;
• Cushing's syndrome, adrenal or pituitary insufficiency; poorly controlled diabetes mellitus; or current hypertension with systolic blood pressure ≥ 160 mmHg or diastolic blood pressure ≥ 100 mmHg despite treatment with oral antihypertensive agents;
• History within 6 months prior to first dosing of esophageal or gastric varices, severe ulcer disease, gastrointestinal perforation and/or fistula, gastrointestinal obstruction (including incomplete obstruction requiring parenteral nutrition), intra-abdominal abscess, or acute gastrointestinal bleeding;

Sponsors & Collaborators

• Shandong Cancer Hospital and Institute: lead

Study Sites (1)

Jinan, Shandong 0531

Jinan, China

RECRUITING

Related Publications (8)

• Miyawaki T, Naito T, Yabe M, Kodama H, Nishioka N, Miyawaki E, Mamesaya N, Kobayashi H, Omori S, Wakuda K, Ono A, Kenmotsu H, Murakami H, Mori K, Harada H, Takahashi K, Takahashi T. Impact of weight loss on treatment with PD-1/PD-L1 inhibitors plus chemotherapy in advanced non-small-cell lung cancer. Support Care Cancer. 2022 Feb;30(2):1633-1641. doi: 10.1007/s00520-021-06572-4. Epub 2021 Sep 22.

  PMID: 34550461 BACKGROUND

• Betts KA, Gao S, Ray S, Schoenfeld AJ. Real-world safety of first-line immuno-oncology combination therapies for advanced non-small-cell lung cancer. Future Oncol. 2024 Apr;20(13):851-862. doi: 10.2217/fon-2023-0612. Epub 2024 Jan 19.

  PMID: 38240151 BACKGROUND

• Hariyanto TI, Kurniawan A. Appetite problem in cancer patients: Pathophysiology, diagnosis, and treatment. Cancer Treat Res Commun. 2021;27:100336. doi: 10.1016/j.ctarc.2021.100336. Epub 2021 Feb 13.

  PMID: 33607591 BACKGROUND

• Yeom E, Yu K. Understanding the molecular basis of anorexia and tissue wasting in cancer cachexia. Exp Mol Med. 2022 Apr;54(4):426-432. doi: 10.1038/s12276-022-00752-w. Epub 2022 Apr 6.

  PMID: 35388147 BACKGROUND

• Hong SH, Choi KM. Gut hormones and appetite regulation. Curr Opin Endocrinol Diabetes Obes. 2024 Jun 1;31(3):115-121. doi: 10.1097/MED.0000000000000859. Epub 2024 Mar 21.

  PMID: 38511400 BACKGROUND

• Rubinic I, Kurtov M, Likic R. Novel Pharmaceuticals in Appetite Regulation: Exploring emerging gut peptides and their pharmacological prospects. Pharmacol Res Perspect. 2024 Aug;12(4):e1243. doi: 10.1002/prp2.1243.

  PMID: 39016695 BACKGROUND

• Fearon K, Strasser F, Anker SD, Bosaeus I, Bruera E, Fainsinger RL, Jatoi A, Loprinzi C, MacDonald N, Mantovani G, Davis M, Muscaritoli M, Ottery F, Radbruch L, Ravasco P, Walsh D, Wilcock A, Kaasa S, Baracos VE. Definition and classification of cancer cachexia: an international consensus. Lancet Oncol. 2011 May;12(5):489-95. doi: 10.1016/S1470-2045(10)70218-7. Epub 2011 Feb 4.

  PMID: 21296615 BACKGROUND

• Argiles JM, Lopez-Soriano FJ, Stemmler B, Busquets S. Cancer-associated cachexia - understanding the tumour macroenvironment and microenvironment to improve management. Nat Rev Clin Oncol. 2023 Apr;20(4):250-264. doi: 10.1038/s41571-023-00734-5. Epub 2023 Feb 20.

  PMID: 36806788 BACKGROUND

MeSH Terms

Conditions

Body Weight

Condition Hierarchy (Ancestors)

Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Jinbo Yue, Dorcter

  Shandong Cancer Hospital and Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jinbo Yue, Dorcter

CONTACT

0531-67626442; jbyue@sdfmu.edu.cn

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Radiation Oncology Department

Model Details: This is a randomized, controlled, prospective, multicenter study evaluating nano-crystalline megestrol acetate plus first-line chemotherapy in patients with advanced pancreatic cancer-related anorexia-cachexia syndrome. Treatment-naïve patients with locally advanced or metastatic pancreatic ductal adenocarcinoma meeting pre-cachexia or cachexia criteria will be randomized 1:1 to receive nano-crystalline megestrol acetate (625 mg/day for up to 12 weeks) with chemotherapy or chemotherapy alone. The primary endpoint is ≥5% weight gain at Week 12. Secondary endpoints include appetite, OS, PFS, body composition, quality of life, and safety. Open-label follow-up is up to one year.

Study Record Dates

• First Submitted: January 23, 2026
• First Posted: February 13, 2026
• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): December 30, 2027
• Study Completion (Estimated): February 20, 2028
• Last Updated: April 27, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)