Megestrol Acetate Oral Suspension for Cachexia in Patients With cStage III Gastric/Gastroesophageal Junction Adenocarcinoma Receiving Neoadjuvant Therapy With Serplulimab Combined With SOX

NCT07391826 | Not Yet Recruiting Phase 2

• 1 other identifier: MEGACACHE
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

Brief Summary

This study is an open-label, prospective, randomized controlled phase II clinical study. The purpose is to evaluate the efficacy and safety of megestrol acetate oral suspension for patients with cachexia and cStage III gastric/gastroesophageal junction adenocarcinoma who receive neoadjuvant therapy with serplulimab combined with SOX. This study intends to include 48 patients with locally advanced gastric adenocarcinoma who have not received any treatment, meet the diagnosis of cachexia, and are operable as research subjects. It is expected that 32 patients will be included in the experimental group and 16 patients will be included in the control group, with an inter-group ratio of approximately 2:1. After signing the informed consent, the patients will be screened and meet the inclusion and exclusion criteria. The groups will be assigned according to the random results. The patients will receive or not receive megestrol acetate oral suspension during the 3 cycles of serplulimab SOX regimen before surgery. After the second and third cycles of medication, the efficacy of neoadjuvant therapy and the possibility of radical gastric cancer D2 resection will be evaluated by imaging examinations, and radical gastric cancer surgery will be performed within 2-6 weeks after the third dose is completed. The treatment of postoperative patients will be decided by clinicians and patients based on actual clinical diagnosis and treatment. Patients must be given study drug treatment within 7 days after randomization. The dosing window for each cycle after the first dose is ±7 days. Before each dose, patients must complete the corresponding examinations specified in the protocol to assess the safety and tolerability of the treatment. Dosage regimen:

• Treatment group: megestrol acetate oral suspension + serplulimab + SOX
• Control group: serplulimab + SOX

Conditions

Stage III Gastric Cancer

Keywords

gastric/gastroesophageal junction adenocarcinoma

Outcome Measures

Primary Outcomes (1)

• The proportion of patients whose weight did not decrease

  The proportion of subjects with a weight loss of no more than 2 kg from the initiation of neoadjuvant therapy to the time immediately preceding radical surgery.

  From the date of the first neoadjuvant therapy until the date of radical surgery,assessed up to 6 months

Secondary Outcomes (10)

• appetite improve

  From the date of the first neoadjuvant therapy until the date of radical surgery,assessed up to 6 months

• Quality of life by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire(EORTC QLQ-C30)

  From the date of the first neoadjuvant therapy until the date of radical surgery,assessed up to 6 months

• CRP indicators

  From the date of the first neoadjuvant therapy until the date of radical surgery,assessed up to 6 months

• IL-6 indicators

  From the date of the first neoadjuvant therapy until the date of radical surgery,assessed up to 6 months

• TNF-α indicators

  From the date of the first neoadjuvant therapy until the date of radical surgery,assessed up to 6 months

Other Outcomes (1)

• Immune microenvironment alterations during treatment

  From the date of the first neoadjuvant therapy until the date of radical surgery,assessed up to 6 months

Study Arms (2)

Treatment group

EXPERIMENTAL

megestrol acetate oral suspension + serplulimab + SOX

Drug: megestrol acetate oral suspension + serplulimab + SOX

control group

EXPERIMENTAL

serplulimab + SOX

Drug: serplulimab + SOX

Interventions

serplulimab + SOX DRUG

serplulimab + SOX

control group

megestrol acetate oral suspension + serplulimab + SOX DRUG

megestrol acetate oral suspension + serplulimab + SOX

Treatment group

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Voluntary signing of written informed consent;
• Age at enrollment ≥ 18 years and ≤ 80 years;
• Eastern Cooperative Oncology Group (ECOG, see Appendix 4) physical status score of 0-2;
• Expected survival ≥ 6 months;
• According to the 8th edition of AJCC gastric cancer staging, patients with cStage III (cT3-4aN1-3M0) assessed by abdominal CT and diagnosed with G/GEJ adenocarcinoma by gastroscopy and pathology, and only Siewert III type and Siewert II type subjects who do not require combined thoracotomy are allowed to be enrolled in gastroesophageal junction (GEJ) cancer;
• Meet the diagnostic criteria for cachexia (based on Fearon diagnostic criteria).
• Diagnostic criteria for cachexia: any of the following combined with anorexia or systemic inflammatory response: (1) involuntary weight loss of \>5% in 6 months; (2) BMI \<18.5 kg/m2, and involuntary weight loss of \>2% in 6 months; (3) limb skeletal muscle index meets the diagnostic criteria for sarcopenia (male \<7.26 kg/m²; female \<5.45 kg/m²), and involuntary weight loss of \>2% in 6 months.
• Before enrollment, a gastrointestinal surgeon and an imaging physician jointly evaluated and determined that the tumor was cStage III and eligible for R0 resection with the purpose of cure. The patient agreed to undergo radical surgery and was judged by the surgeon to have no contraindications to surgery;
• No previous systemic treatment for the current disease, including surgical treatment, anti-tumor chemoradiotherapy/immunotherapy, etc.;
• Good cardiac function, and resection with the purpose of cure can be performed. If clinically indicated, patients with underlying ischemic, valvular heart disease or other severe heart disease should be evaluated by a cardiologist before surgery;
• Normal function of major organs
• Female patients must meet the following requirements:
• Menopausal (defined as no menstruation for at least 1 year, and no other confirmed cause other than menopause), or surgical sterilization (ovarian and/or uterine removal), or patients of childbearing potential must meet the following requirements at the same time:
• A negative pregnancy test within 7 days before the first medication;
• Agree to use contraceptive measures with an annual failure rate of \< 1% or maintain abstinence (avoid heterosexual intercourse) (from signing the informed consent form to at least 120 days after the last dose of the trial drug, and at least 9 months after surgery (contraceptive methods with an annual failure rate of \< 1% include bilateral tubal ligation, male sterilization, correct use of hormonal contraceptives that can inhibit ovulation, hormone-releasing intrauterine devices, and copper-containing intrauterine devices.);

You may not qualify if:

• The patient has had other malignant tumors in the past (within 5 years) or concurrently. Patients with cured localized tumors, such as basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial bladder cancer, prostate carcinoma in situ, cervical carcinoma in situ, breast carcinoma in situ, stage I lung cancer, stage I colorectal cancer, etc. can be included in the group;
• Patients who are preparing for or have received organ or bone marrow transplantation in the past;
• Patients who have received blood transfusion within 2 weeks before the first medication, or have a history of bleeding, and have any severe bleeding events of grade 3 or above in CTCAE5.0 within 4 weeks before screening;
• Patients with abnormal coagulation function and bleeding tendency (INR is in the normal value \> 1.5 without the use of anticoagulants); patients treated with anticoagulants or vitamin K antagonists such as warfarin, heparin or its analogs; On the premise that the international normalized ratio (INR) of prothrombin time is ≤1.5, low-dose warfarin (1 mg orally, once a day) or low-dose aspirin (daily dose not exceeding 100 mg) is allowed for preventive purposes;
• Arterial/venous thrombotic events within 6 months before screening, such as cerebrovascular accident (including transient ischemic attack), deep vein thrombosis (except for venous thrombosis caused by intravenous catheterization during previous chemotherapy, which is judged by the researcher to have been cured) and pulmonary embolism;
• Myocardial infarction and poorly controlled arrhythmia (including QTc interval ≥450 ms for men and ≥470 ms for women) within 6 months before the first medication (QTc interval is calculated by Fridericia formula);
• NYHA standard III-IV heart failure or cardiac ultrasound examination: LVEF (left ventricular ejection fraction) \<50%;
• Urinalysis indicates urine protein ≥++ and confirms that the 24-hour urine protein quantification is \>1.0 g;
• Pleural effusion or peritoneal effusion with clinical symptoms that require clinical intervention;
• Human immunodeficiency virus (HIV) infection;
• Active pulmonary tuberculosis;
• Long-term unhealed wounds or incompletely healed fractures;
• Patients with past or current interstitial pneumonia, pneumoconiosis, radiation pneumonia, drug-related pneumonia, severe lung function impairment, etc., which may interfere with the detection and treatment of suspected drug-related pulmonary toxicity;
• Patients with known active or suspected autoimmune diseases, except those who are in a stable state of the disease at the time of enrollment (systemic immunosuppressant therapy is not required);
• Patients with a history of severe chronic autoimmune diseases, such as systemic lupus erythematosus, etc.; patients with a history of inflammatory bowel diseases such as ulcerative colitis and Crohn's disease, and a history of chronic diarrheal diseases such as irritable bowel syndrome; patients with a history of sarcoidosis or tuberculosis; patients with a history of active hepatitis B, hepatitis C, and HIV infection; patients with well-controlled non-severe immune diseases, such as dermatitis, arthritis, psoriasis, etc. can be enrolled. Patients with hepatitis B virus titer \< 500 copies/ml can be enrolled;

Sponsors & Collaborators

• The First Affiliated Hospital with Nanjing Medical University: lead

Study Sites (1)

First Affiliated Hospital of Nanjing Medical Unviersity

Nanjing, Jiangsu, 210000, China

Location

MeSH Terms

Conditions

Stomach Neoplasms

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 2, 2025
• First Posted: February 6, 2026
• Study Start: February 15, 2026
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2027
• Last Updated: February 6, 2026

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL

Locations

CN (1)