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

Phase

Condition

Chemotherapy

Diabetes Prevention

Weight Loss

Treatment

Megestrol Acetate

Clinical Study ID

NCT06998758

E2025078

Ages 18-75
All Genders

Study 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.

Eligibility Criteria

Inclusion

Inclusion Criteria:

Adult males and females aged between 18 and 75 years old.
Histologically confirmed colorectal adenocarcinoma.
Immunohistochemistry showing pMMR or MSI status determined as MSS.
Clinical stage cTxN1-2M0, with or without MRF positivity, and with or without EMVIpositivity.
ECOG performance status 0-1, with a life expectancy of ≥6 months.
Deemed suitable for preoperative mFOLFOX6 neoadjuvant chemotherapy followingmultidisciplinary team discussion.
Written informed consent has been obtained from the patients.

Exclusion

Exclusion Criteria:

Patients with cardiac arrhythmias requiring anti-arrhythmic treatment (excluding β-blockers or digoxin), symptomatic coronary artery disease or myocardial ischemia (myocardial infarction within the past 6 months), or congestive heart failuregreater than NYHA Class II.
Patients with poorly controlled severe hypertension.
Patients with a history of HIV infection or active chronic hepatitis B or C (withhigh-copy viral DNA).
Patients with active tuberculosis (TB) who are receiving anti-tuberculosis treatmentor have received anti-tuberculosis treatment within 1 year prior to screening.
Patients with other active severe clinical infections (per NCI-CTC v.5.0).
Patients who have previously received chemotherapy.
Patients with a history of seizures requiring treatment (e.g., steroids oranti-epileptic therapy).
Patients with drug abuse or medical, psychological, or social conditions that mayinterfere with study participation or outcome assessment.
Patients with a known or suspected allergy to the study drug or any agentsadministered in relation to the trial.
Patients with any unstable condition that may jeopardize patient safety orcompliance.
Pregnant or breastfeeding women, or fertile women not using adequate contraception.
Patients who refuse to sign the informed consent form.

Study Design

Megestrol Acetate

November 11, 2025

December 31, 2028

Study 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).

Connect with a study center

The Sixth Affiliated Hospital of Sun-Yat sen University
Guangzhou, Guangdong 510065
China
Site Not Available
The Sixth Affiliated Hospital of Sun-Yat sen University
Guangzhou 1809858, Guangdong 1809935 510065
China
Active - Recruiting

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