A Phase II Single-Arm Study of High-Bioavailability Curcumin as Neoadjuvant Chemoradiotherapy in Mid-to-Low Rectal Cancer: Integrated Clinical and Translational Analysis of Tumor Tissue

Summary

This clinical study investigates the anti-inflammatory and anti-cancer properties of a high-bioavailability formulation of curcumin (BCM-95) in patients with mid-to-low rectal cancer receiving neoadjuvant chemoradiotherapy (nCRT). Curcumin, a polyphenolic compound derived from Curcuma longa, has demonstrated potent anti-inflammatory and anti-neoplastic activities through the modulation of multiple molecular signaling pathways. It has been recognized by the U.S. Food and Drug Administration (FDA) as "Generally Recognized as Safe" (GRAS; GRN No. 686), with an excellent safety profile when administered orally. Reported adverse effects are rare and primarily related to interference with bile secretion or iron metabolism.

Despite its biological potential, conventional curcumin exhibits extremely low oral bioavailability due to its lipophilic nature, rapid metabolism, and systemic elimination. Clinical studies have reported that even at an oral dose of 12 grams per day, the maximum plasma concentration reaches only about 0.051 mg/mL, with up to 75% of the administered dose excreted in feces. To overcome this limitation, the current trial utilizes a curcumin formulation with enhanced absorption (BCM-95), which combines curcumin with essential oils of turmeric to improve systemic bioavailability.

The primary objective of this single-arm, phase II trial is to evaluate whether oral curcumin supplementation can mitigate radiation-induced gastrointestinal toxicity-particularly radiation enteritis-during neoadjuvant chemoradiotherapy for rectal cancer. The secondary objectives include assessing its effect on treatment response, such as the pathological complete response (pCR) rate, tumor regression grade, and patient-reported outcomes related to bowel function and quality of life.

In addition, a translational research component is embedded within this study. Serial tumor tissue and blood samples will be collected at predefined time points to explore the molecular and immunological mechanisms underlying curcumin's therapeutic effects. Analyses will include assessments of inflammatory cytokines, oxidative stress markers, and tumor microenvironmental changes using molecular and histopathologic methods.

Overall, this study aims to provide both clinical and mechanistic evidence supporting the potential of high-bioavailability curcumin as a safe, adjunctive therapeutic strategy to improve treatment tolerance and oncologic outcomes in rectal cancer patients undergoing chemoradiotherapy.

Conditions

• Rectal Cancer
• Locally Advanced Rectal Cancer
• Radiation-Induced Enteritis
• Radiation Proctitis
• Chemoradiotherapy-Related Toxicity

Interventions

DIETARY_SUPPLEMENT

Curcumin (BCM-95®)

Participants will receive oral high-bioavailability curcumin (BCM-95®) 3 g per day, divided into two doses, during the full course of standard neoadjuvant chemoradiotherapy (nCRT) for mid-to-low rectal adenocarcinoma. Treatment starts on day one of nCRT and continues until its completion. The curcumin formulation (BCM-95®) combines curcuminoids with turmeric essential oils to improve systemic absorption and bioavailability. All participants receive institutional standard nCRT, including: Radiotherapy: either long-course (50.4 Gy/28 fractions) or short-course (25 Gy/5 fractions). Chemotherapy: fluoropyrimidine-based regimens such as TEGAFOX, FOLFOX, or UFUR. Curcumin capsules are taken orally after meals. The study evaluates whether curcumin can reduce radiation-induced gastrointestinal toxicity and enhance tumor response. Translational analyses of tumor and blood samples will further investigate its anti-inflammatory and anti-cancer mechanisms.

Sponsors & Collaborators

• Chang Gung Memorial Hospital

  lead OTHER

Principal Investigators

• Shu-Huan Huang, MD. · Chang Gung Memorial Hospital

Study Design

Allocation

NA

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

20 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2026-01-01

Primary Completion

2028-12-31

Completion

2028-12-31

Countries

• Taiwan

Study Locations