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
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 72
- 试验地点
- 1
- 主要终点
- Incidence of Grade ≥3 Gastrointestinal Toxicity (Enteritis or Proctitis) During Neoadjuvant Chemoradiotherapy
研究概览
简要总结
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.
详细描述
This Phase II single-arm clinical trial investigates the safety, tolerability, and therapeutic potential of high-bioavailability curcumin (BCM-95®) administered concurrently with neoadjuvant chemoradiotherapy (nCRT) in patients with mid- to low-rectal adenocarcinoma. The study is designed and conducted at Chang Gung Memorial Hospital, Linkou (Taiwan), under IRB approval and in accordance with Good Clinical Practice (GCP) guidelines.
Scientific Background and Rationale
Curcumin (diferuloylmethane) is a hydrophobic polyphenol extracted from Curcuma longa with extensive anti-inflammatory, antioxidant, and anti-neoplastic properties mediated through suppression of NF-κB, STAT3, COX-2, and multiple cell-signaling pathways. In preclinical models, curcumin inhibits radiation-induced activation of NF-κB and enhances radiosensitivity of colorectal-cancer cell lines, while protecting normal intestinal epithelium from irinotecan-induced mucosal injury by mitigating oxidative and endoplasmic-reticulum stress. Despite its excellent oral safety record (FDA GRAS Notice No. 686), conventional curcumin suffers from extremely low systemic bioavailability due to poor solubility and rapid metabolism.
BCM-95® Curcumin is a patented formulation that combines 95 % curcuminoids with turmeric essential oils, improving absorption approximately seven-fold compared with standard curcumin. Given its dual ability to radiosensitize tumor tissue and protect normal mucosa, BCM-95® Curcumin may attenuate radiation-induced enteritis while enhancing tumor regression and pathological complete-response (pCR) rates following nCRT.
Objectives
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
盲法说明
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).
入排标准
- 年龄范围
- 20 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •(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
排除标准
- •(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
结局指标
主要结局
Incidence of Grade ≥3 Gastrointestinal Toxicity (Enteritis or Proctitis) During Neoadjuvant Chemoradiotherapy
时间窗: From the start of chemoradiotherapy to 3 weeks after completion of radiotherapy (approximately 8 weeks total)
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.
次要结局
- Vienna Rectoscopy Score for Radiation-Induced Proctitis(Baseline, 2 ± 1 weeks, and 12 ± 1 weeks after completion of radiotherapy)