Megestrol acetate to prevent weight loss during preoperative chemotherapy for locally advanced colorectal cancer

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

This trial tests whether taking megestrol acetate during mFOLFOX6 neoadjuvant chemotherapy can prevent weight loss and improve appetite in adults with locally advanced colorectal cancer.

Quick facts

• Phase: PHASE3
• Study type: Interventional
• Enrollment: 60 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Sixth Affiliated Hospital, Sun Yat-sen University (other)
• Drugs / interventions: chemotherapy
• Locations: 1 site (Guangzhou, Guangdong)
• Trial ID: NCT06998758 on ClinicalTrials.gov

What this trial studies

This is an open-label, multicenter, randomized Phase 3 trial comparing standard neoadjuvant mFOLFOX6 chemotherapy alone versus mFOLFOX6 combined with oral megestrol acetate 625 mg/day given during the six neoadjuvant cycles. Eligible patients are randomized 1:1 and all undergo planned radical surgery after completing neoadjuvant therapy, with pathological response guiding further adjuvant treatment. The study measures changes in weight, appetite, nutritional status, and chemotherapy-related gastrointestinal toxicities, while monitoring safety of megestrol acetate. Outcomes include rates of weight loss prevention, treatment tolerability, pathological complete response, and postoperative recovery metrics.

Who should consider this trial

Good fit: Adults aged 18–75 with histologically confirmed locally advanced colorectal adenocarcinoma (cTxN1-2M0), pMMR/MSS status, ECOG 0–1, and planned for preoperative mFOLFOX6 are ideal candidates.

Not a fit: Patients with significant cardiac disease, poorly controlled hypertension, active high-copy hepatitis or HIV, or those not receiving mFOLFOX6 neoadjuvant therapy are unlikely to benefit or are excluded.

Why it matters

Potential benefit: If successful, patients may maintain or regain weight, have better appetite, and experience fewer nutrition-related complications during neoadjuvant chemotherapy.

How similar studies have performed: Previous studies in metastatic colorectal cancer have shown megestrol acetate can improve appetite, increase body weight, and enhance quality of life, but using it specifically during neoadjuvant mFOLFOX6 for locally advanced disease is novel.

Eligibility criteria

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 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.

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 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.

Where this trial is running

Guangzhou, Guangdong

• The Sixth Affiliated Hospital of Sun-Yat sen University — Guangzhou, Guangdong, China (RECRUITING)

Study contacts

• Principal investigator: Jun Huang, PhD. — Sun Yat-sen University
• Study coordinator: Jun Huang, PhD.

Conditions: Neoadjuvant Chemotherapy, Weight Loss, Megestrol Acetate