NCT06998758

Megestrol Acetate in Improving Neoadjuvant Chemotherapy-Related Weight Loss in Locally Advanced CRC

Megestrol Acetate in Improving Neoadjuvant Chemotherapy-Related Weight Loss in Patients With Locally Advanced Colorectal Cancer: A Multicenter Randomized Controlled Clinical Trial

• Status: Recruiting
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 60 (estimated)
• Sponsor: Sixth Affiliated Hospital, Sun Yat-sen University · Academic / Other
• Sex: All
• Age: 18 Years – 75 Years
• Healthy volunteers: Not accepted

Summary

Cancer-associated anorexia, a debilitating condition characterized by progressive appetite loss in oncology patients, contributes to pancytopenia, sarcopenia, and adipose tissue depletion. Megestrol acetate (MA) improves appetite and promotes weight gain through multiple mechanisms, playing a crucial role in the nutritional management of cancer patients. Total mesorectal excision (TME) following neoadjuvant chemotherapy has become the standard treatment strategy for patients with locally advanced colorectal cancer (LACRC). Despite its oncological benefits, neoadjuvant chemotherapy frequently induces grade ≥2 gastrointestinal toxicities (including nausea, emesis, and diarrhea) that exacerbate malnutrition through appetite suppression and negative energy balance. Previous studies have demonstrated that combining MA with first-line maintenance chemotherapy in patients with metastatic colorectal cancer significantly improves appetite, increases body weight, enhances quality of life, and improves prognosis. However, the safety and efficacy of MA during the neoadjuvant treatment phase of LACRC remain unclear. This multicenter, randomized controlled clinical trial aims to evaluate the effects of MA on chemotherapy--related weight loss, anorexia, nutritional status, and chemotherapy tolerance in patients with LACRC undergoing neoadjuvant chemotherapy. Additionally, this study will assess the safety profile of MA in this clinical setting.

Detailed description

This clinical trial is an open-label, prospective, multicenter, randomized study. The aims of this study are to evaluate the effects of megestrol acetate (MA) on ameliorating neoadjuvant chemotherapy-related weight loss, anorexia, nutritional deterioration, andChemotherapy-related adverse events in patients with locally advanced colorectal cancer (LACRC), while comprehensively assessing its safety profile. Eligible participants will be randomly assigned in a 1:1 ratio to either the experimental group or the control group. Participants in the experimental group will receive 6 cycles of neoadjuvant chemotherapy regimen of mFOLFOX6 (intravenous oxaliplatin 85 mg/m2, leucovorin 400 mg/m2, 5-fluorouracil 400 mg/m2, and 5-fluorouracil 2400 mg/m2 continuous pumping for 48 hours) administered every 14 days, combined with oral MA suspension at a dose of 625 mg/day. MA treatment will be maintained until the completion of neoadjuvant chemotherapy. Participants in the control group will receive 6 cycles of the mFOLFOX6 neoadjuvant chemotherapy regimen without concurrent administration of MA. Subjects in both the experimental and control groups will undergo radical surgical treatment after completing the neoadjuvant therapy. Those achieving pCR based on postoperative pathology will be regularly followed up according to the follow-up protocol. Participants who do not achieve pCR will receive six cycles of adjuvant therapy after surgery, followed by regular follow-up assessments as outlined in the protocol after completing the final cycle of adjuvant therapy. The primary outcome of this study is the incidence of weight loss (defined as \>5% body weight reduction during neoadjuvant therapy). Secondary objectives include: 1) Appetite evaluation; 2) Nutritional parameter dynamics; 3) Quality of life (QoL) assessment with the EORTC QLQ-C30 questionnaire; 4) Incidence of neoadjuvant chemotherapy-related adverse events; 5) Oncological response; 6) Surgical morbidity; 7) Postoperative recovery metrics: time to first flatus/bowel movement, length of postoperative hospitalization, and 30-day readmission rates; 8) Survival outcomes: 1-year disease-free survival (DFS), Overall survival (OS).

Conditions

• Neoadjuvant Chemotherapy
• Weight Loss

Interventions

Type	Name	Description
DRUG	Megestrol Acetate	Oral megestrol acetate at 625 mg/day is given from the beginning to the end of neoadjuvant chemotherapy.

Timeline

• Start date: 2025-11-11
• Primary completion: 2027-05-10
• Completion: 2028-12-31
• First posted: 2025-05-31
• Last updated: 2025-12-12

Locations

1 site across 1 country: China