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

NCT06998758 | Recruiting Phase 3

• 1 other identifier: E2025078
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Neoadjuvant Chemotherapy; Weight Loss

Keywords

Megestrol Acetate

Outcome Measures

Primary Outcomes (1)

• Incidence of weight loss

  the rate of weight loss

  1 year

Secondary Outcomes (11)

• Appetite assessment

  1 year

• Changes in nutritional indicators

  1 year

• Quality of life assessment

  1 year

• AEs related to NCT

  1 year

• Tumor response assessment of neoadjuvant chemotherapy

  1 year

Study Arms (2)

mFOLFOX6 + Megestrol Acetate

EXPERIMENTAL

Patients from experimental group receive six cycles of neoadjuvant chemotherapy with mFOLFOX6 (oxaliplatin 85 mg/m², leucovorin calcium 400 mg/m², fluorouracil 400 mg/m², and fluorouracil 2400 mg/m² continuous infusion over 48 hours on day 1) every 2 weeks and megestrol acetate at 625 mg/day by oral until the end of neoadjuvant chemotherapy.

Drug: Megestrol Acetate

mFOLFOX6

NO INTERVENTION

Patients from this group receive six cycles of neoadjuvant chemotherapy with mFOLFOX6 (oxaliplatin 85 mg/m², leucovorin calcium 400 mg/m², fluorouracil 400 mg/m², and fluorouracil 2400 mg/m² continuous infusion over 48 hours on day 1) every 2 weeks

Interventions

Megestrol Acetate DRUG

Oral megestrol acetate at 625 mg/day is given from the beginning to the end of neoadjuvant chemotherapy.

mFOLFOX6 + Megestrol Acetate

Eligibility Criteria

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

You may qualify if:

• 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 EMVI positivity.
• ECOG performance status 0-1, with a life expectancy of ≥6 months.
• Deemed suitable for preoperative mFOLFOX6 neoadjuvant chemotherapy following multidisciplinary team discussion.
• Written informed consent has been obtained from the patients.

You may not qualify if:

• 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 failure greater than NYHA Class II.
• Patients with poorly controlled severe hypertension.
• Patients with a history of HIV infection or active chronic hepatitis B or C (with high-copy viral DNA).
• Patients with active tuberculosis (TB) who are receiving anti-tuberculosis treatment or 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 or anti-epileptic therapy).
• Patients with drug abuse or medical, psychological, or social conditions that may interfere with study participation or outcome assessment.
• Patients with a known or suspected allergy to the study drug or any agents administered in relation to the trial.
• Patients with any unstable condition that may jeopardize patient safety or compliance.
• Pregnant or breastfeeding women, or fertile women not using adequate contraception.
• Patients who refuse to sign the informed consent form.

Sponsors & Collaborators

• Sixth Affiliated Hospital, Sun Yat-sen University: lead

Study Sites (1)

The Sixth Affiliated Hospital of Sun-Yat sen University

Guangzhou, Guangdong, 510065, China

RECRUITING

MeSH Terms

Conditions

Weight Loss

Interventions

Megestrol Acetate

Condition Hierarchy (Ancestors)

Body Weight Changes; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Megestrol; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• Jun Huang, PhD.

  Sun Yat-sen University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jun Huang, PhD.

CONTACT

+86-13926451242; huangj97@mail.sysu.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: May 8, 2025
• First Posted: May 31, 2025
• Study Start: November 11, 2025
• Primary Completion (Estimated): May 10, 2027
• Study Completion (Estimated): December 31, 2028
• Last Updated: December 12, 2025

Record last verified: 2025-12

Locations

CN (1)