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

NCT07248020 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: 202501055A0
• Study Type: interventional
• Target: 72
• Locations: 1 country
• Sites: 1

Brief 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

Keywords

Curcumin; Rectal cancer; Chemoradiotherapy

Outcome Measures

Primary Outcomes (1)

• Incidence of Grade ≥3 Gastrointestinal Toxicity (Enteritis or Proctitis) During Neoadjuvant Chemoradiotherapy

  The primary endpoint is the incidence of grade ≥3 gastrointestinal adverse events, including enteritis or proctitis, occurring during neoadjuvant chemoradiotherapy (nCRT). Toxicities will be assessed and graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 5.0, and validated by Radiation Therapy Oncology Group (RTOG) and European Organisation for Research and Treatment of Cancer (EORTC) criteria. Clinical symptoms (abdominal pain, diarrhea, bloody stool, tenesmus, nausea) will be documented by investigators and research nurses. Colonoscopic assessment using the Vienna Rectoscopy Score will be performed 2-3 weeks after radiotherapy completion to evaluate acute radiation proctitis.

  From the start of chemoradiotherapy to 3 weeks after completion of radiotherapy (approximately 8 weeks total)

Secondary Outcomes (1)

• Vienna Rectoscopy Score for Radiation-Induced Proctitis

  Baseline, 2 ± 1 weeks, and 12 ± 1 weeks after completion of radiotherapy

Other Outcomes (4)

• Three-Year Disease-Related Treatment Failure Rate

  From completion of chemoradiotherapy to 3 years after surgery

• Five-Year Overall Survival

  From the start of chemoradiotherapy to 5 years post-treatment

• Molecular and Immune Marker Changes in Tumor and Adjacent Tissues

  Baseline, post-radiotherapy (approximately 6 weeks), and at surgery (approximately 16-20 weeks after treatment start)

Study Arms (1)

High-Bioavailability Curcumin (BCM-95®) Plus Neoadjuvant Chemoradiotherapy

EXPERIMENTAL

Participants with stage II-III mid-to-low rectal adenocarcinoma will receive oral high-bioavailability curcumin (BCM-95®) 3 g per day throughout the entire course of standard neoadjuvant chemoradiotherapy (nCRT). nCRT will include: Short-course radiotherapy: 25 Gy in 5 fractions with systemic chemotherapy as per institutional protocol. Curcumin administration starts on the first day of chemoradiotherapy and continues until completion. The aim is to evaluate whether curcumin reduces radiation-induced gastrointestinal toxicity (enteritis/proctitis), enhances tumor response, and improves treatment tolerability. Translational analyses of tumor and blood samples will explore curcumin's anti-inflammatory and anti-cancer molecular mechanisms.

Dietary Supplement: Curcumin (BCM-95®)

Interventions

Curcumin (BCM-95®) DIETARY_SUPPLEMENT

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.

Also known as: High-Bioavailability Curcumin, BCM95 Curcumin

High-Bioavailability Curcumin (BCM-95®) Plus Neoadjuvant Chemoradiotherapy

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• (A) Males and females more than 20 years of age (B) Signed informed consent (C) Patients with a pathologically proven rectal adenocarcinoma located less than 10 cm to the anus.
• (D) Clinical staging (AJCC 8th ed.): T2-4 N0 M0 or T any N1-2 M0 (E) Distal metastasis has been excluded by imaging study: by chest-to-pelvic computed tomography or Positron Emission Tomography (F) Preoperative pelvic staging by pelvic Magnetic Resonance Imaging (preferred) or trans-rectal ultrasound (G) Patients with WHO/ECOG performance scale 0 or 1

You may not qualify if:

• (A) Refuse to sign the informed consent (B) Distal metastasis revealed by the imaging study (C) Patients does not receive radiotherapy (D) Unable to receive further curative resection (E) Patients receive tumor resection before the neoadjuvant treatment (F) Patients have history of more than 5 Gy of pelvic radiation (G) Patients in pregnancy or lactation status (H) Patients have allergic history to curcumin, 5-fluouracil or oxaliplatin (I) Patients of childbearing potential can not cooperate with appropriate contraceptive method (oral, injectable, or implantable hormonal contraceptive; tubal ligation; intra-uterine device; barrier contraceptive with spermicide; or vasectomized partner) (J) Patients with any concurrent malignancy; patients with history of malignancy should be cancer-free for more than 5 years (K) Patients with New York Heart Association (NYHA) class III or IV heart failure, unstable angina pectoris, unstable cardiac arrhythmia or tachycardia (heart rate \> 100 beats/minute) (L) Patients have concurrent uncontrolled medical conditions, such as illness ongoing or requiring IV antibiotics, severe chronic renal failure (eGFR \<30 mL/min/1.73m2) or severe active hepatitis(AST/ALT\>3x upper normal limit)、Total Bilirubin\>2 mg/dl (M) Patients with previous or current drug abuse (N) Patients underwent major surgery within 28 days of study enrollment (except diverting colostomy) (O) Patients have Familial Adenomatosis Polyposis Coli (FAP), Hereditary Non-Polyposis Colorectal Cancer (HNPCC), active Crohn's disease or active ulcerative Colitis (P) Patients have known dipyrimidine dehydrogenase deficiency (DPD) (Q) Patients with congenital iron metabolic or hematopoietic diseases (R) Patients with synchronous colon cancer (S) The Patients with hematologic abnormalities (INR \> 1.5, white blood cell (WBC) count \< 3,000/μL, absolute neutrophil count (ANC) \< 1,500/μL, platelet count \< 100,000/μL, hemoglobin \< 9.0 g/dL not caused by tumor treatment) or known hematologic diseases (aplastic anemia, myelodysplastic syndrome (MDS), leukemia, malignant lymphoma, multiple myeloma, hereditary hematologic diseases such as thalassemia, sickle cell anemia, etc.).
• (T) The patient has diabetes mellitus (U) The patient is taking the immunosuppressants Cyclosporine, Tacrolimus, Sirolimus, and Everolimus and antigoagulants (warfarin、NOACs、aspirin) (V) Patients with The medical, psychological, or social condition that, in the opinion of the investigator, may increase the patient's risk or limit the patient's adherence with study requirements

Sponsors & Collaborators

• Chang Gung Memorial Hospital: lead

Study Sites (1)

Linkou Chang Gung Memorial Hospital

Taoyuan District, Taoyuan, 333, Taiwan

Location

Related Publications (7)

• Ouyang M, Luo Z, Zhang W, Zhu D, Lu Y, Wu J, Yao X. Protective effect of curcumin against irinotecan-induced intestinal mucosal injury via attenuation of NF-kappaB activation, oxidative stress and endoplasmic reticulum stress. Int J Oncol. 2019 Apr;54(4):1376-1386. doi: 10.3892/ijo.2019.4714. Epub 2019 Feb 11.

  PMID: 30968152 RESULT

• Sandur SK, Deorukhkar A, Pandey MK, Pabon AM, Shentu S, Guha S, Aggarwal BB, Krishnan S. Curcumin modulates the radiosensitivity of colorectal cancer cells by suppressing constitutive and inducible NF-kappaB activity. Int J Radiat Oncol Biol Phys. 2009 Oct 1;75(2):534-42. doi: 10.1016/j.ijrobp.2009.06.034.

  PMID: 19735878 RESULT

• Arun P, Sagayaraj A, Azeem Mohiyuddin SM, Santosh D. Role of turmeric extract in minimising mucositis in patients receiving radiotherapy for head and neck squamous cell cancer: a randomised, placebo-controlled trial. J Laryngol Otol. 2020 Feb 7:1-6. doi: 10.1017/S0022215120000316. Online ahead of print.

  PMID: 32029014 RESULT

• Antony B, Merina B, Iyer VS, Judy N, Lennertz K, Joyal S. A Pilot Cross-Over Study to Evaluate Human Oral Bioavailability of BCM-95CG (Biocurcumax), A Novel Bioenhanced Preparation of Curcumin. Indian J Pharm Sci. 2008 Jul-Aug;70(4):445-9. doi: 10.4103/0250-474X.44591.

  PMID: 20046768 RESULT

• Shehzad A, Wahid F, Lee YS. Curcumin in cancer chemoprevention: molecular targets, pharmacokinetics, bioavailability, and clinical trials. Arch Pharm (Weinheim). 2010 Sep;343(9):489-99. doi: 10.1002/ardp.200900319.

  PMID: 20726007 RESULT

• Ismail NI, Othman I, Abas F, H Lajis N, Naidu R. Mechanism of Apoptosis Induced by Curcumin in Colorectal Cancer. Int J Mol Sci. 2019 May 17;20(10):2454. doi: 10.3390/ijms20102454.

  PMID: 31108984 RESULT

• Jurenka JS. Anti-inflammatory properties of curcumin, a major constituent of Curcuma longa: a review of preclinical and clinical research. Altern Med Rev. 2009 Jun;14(2):141-53.

  PMID: 19594223 RESULT

MeSH Terms

Conditions

Rectal Neoplasms

Interventions

Curcumin

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Diarylheptanoids; Heptanes; Alkanes; Hydrocarbons, Acyclic; Hydrocarbons; Organic Chemicals; Catechols; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic

Study Officials

• Shu-Huan Huang, MD.

  Chang Gung Memorial Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Shu-Huan Huang, MD.

CONTACT

+88633281200; mr0946@cgmh.org.tw

Jeng-Fu You, MD

CONTACT

+88633281200; you3368@cgmh.org.tw

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Masking Details: This study is conducted as an open-label, single-arm trial. Because the investigational product (oral high-bioavailability curcumin, BCM-95®) is administered as a dietary supplement in combination with standard neoadjuvant chemoradiotherapy, blinding of participants and investigators is not feasible. The intervention does not involve a placebo or comparator arm, and all participants receive the same standardized treatment regimen. Safety, efficacy, and translational endpoints will be objectively assessed using predefined clinical and laboratory criteria (CTCAE v5.0, RTOG/EORTC, RECIST v1.1).
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is a single-arm, open-label, phase II interventional study designed to evaluate the safety, tolerability, and therapeutic potential of high-bioavailability curcumin (BCM-95®) administered concurrently with standard neoadjuvant chemoradiotherapy (nCRT) in patients with mid-to-low rectal adenocarcinoma. All participants will receive oral BCM-95® (3 g/day) throughout the entire nCRT period. The study begins with a safety run-in cohort of six patients to confirm dose feasibility and monitor dose-limiting toxicities (DLTs), followed by expansion to a total of 72 patients. The intervention model follows a single-group assignment without randomization or masking. Outcomes include radiation-induced gastrointestinal toxicity, treatment completion, and tumor response. Translational analyses on serial tumor and blood samples will explore curcumin's anti-inflammatory and anti-cancer mechanisms.

Study Record Dates

• First Submitted: November 18, 2025
• First Posted: November 25, 2025
• Study Start: January 1, 2026
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): December 31, 2028
• Last Updated: November 25, 2025

Record last verified: 2025-11

Locations

TW (1)