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
Phase: PHASE2
Conditions: Rectal Cancer, Locally Advanced Rectal Cancer, Radiation-Induced Enteritis, Radiation Proctitis, Chemoradiotherapy-Related Toxicity
Sponsor: Chang Gung Memorial Hospital

Protocol:   BCMRECRAD                                                                                                                                            
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CLINICAL STUDY PROTOCOL 
 
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 
(BCMRECRAD) 
VERSION NO.1 
 DATES: 2025/11/11 
 
 
 
 
 
INVESTIGATORS 
Shu-Huan Huang, Jeng-Fu You, Sum-Fu Chiang, Cheng-En Hsieh 
SITES 
Division of Colon and Rectal Surgery, Chang Gung Memorial Hospital, Linkou, Taiwan 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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Table of Contents 
Section 
Page 
1. Synopsis ...................................................................................................................................4 
2. Introduction and Rationale ........................................................................................................... 8 
3. Objectives and Endpoints ........................................................................................................9 
3.1. Study Objectives ................................................................................................................ 9 
3.2. Study endpoints ................................................................................................................. 9 
4. Study Design............................................................................................................................9 
4.1. Overall Design (Flow Chart) ............................................................................................. 9 
4.2. Number of Patients ........................................................................................................... 11 
4.3. Schedule of Activities (Time-Event scheme) .................................................................. 11 
5. Study Population ....................................................................................................................12 
5.1. Inclusion Criteria .............................................................................................................. 12 
5.2. Exclusion Criteria ............................................................................................................ 12 
5.3. Withdrawal criteria ..................................................................................................................... 13 
6. Treatments .............................................................................................................................13 
6.1. Treatments Administration .............................................................................................. 13 
6.2. Concomitant Therapy ...................................................................................................... 13 
7. Efficacy Assessments ............................................................................................................14 
8. Safety Assessments…………………………………………………………………………14 
9. Adverse Event reporting……………………………………………………………………14 
9.1. Definition and reports of Adverse Events........................................................................ 15 
9.2. Adverse event follow-up .................................................................................................. 16 
10. Criteria for the termination of the trials……………………………………………………16 
11. Statistical Considerations…………………………………………………………………..16 
11.1. Sample Size Determination ............................................................................................16 
11.2. Planned Statistical methods of analysis ..........................................................................17 
11.2.1. Efficacy analyses ......................................................................................................17 
11.2.2. Safety analyses .........................................................................................................17 
11.2.3. Additional analyses ..................................................................................................17 
11.2.4. The level of significance ..........................................................................................17 
11.2.5. Analysis Population ..................................................................................................17 
12. Direct access to source data/documents……………………………………………………18 
13. Ethical considerations………………………………………………………………………18 
14. Data handling and keeping………………………………………………………………….18 
15. Financing and Insurance……………………………………………………………………18 
16. Privacy and Confidentiality 

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Protection……………………………………………………………….…………………18 
17. References..............................................................................................................................19 

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1. Synopsis 
 
 
Protocol Title： 
     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 
Study Objectives： 
    This study aims to investigate the anti-inflammatory and anti-cancer properties of high-
bioavailability curcumin in patients with mid-to-low rectal cancer undergoing neoadjuvant 
chemoradiotherapy. Curcumin is generally considered to have a high safety profile, and its oral 
formulation has been classified by the U.S. Food and Drug Administration (FDA) as “Generally 
Recognized as Safe” (GRAS) (GRAS Notice [GRN] No. 686). Reports of adverse effects related to 
curcumin are rare and primarily involve interference with bile secretion and iron metabolism.[1, 2] 
However, despite numerous molecular studies demonstrating curcumin’s anti-cancer and anti-
inflammatory mechanisms, as well as its excellent oral safety, its oral bioavailability remains extremely 
low due to its lipophilic nature. Previous human studies have shown that even with oral administration 
of 12 grams of curcumin, the serum concentration only reaches 0.051 mg/mL[3], and approximately 
75% of orally administered curcumin is excreted via feces.[4] The primary objective is to evaluate 
whether curcumin can reduce radiotherapy-associated adverse effects, such as radiation-induced 
enteritis, and improve the pathological complete response (pCR) rate to chemoradiotherapy. In 
addition, translational research will be conducted on tumor tissue samples collected at different time 
points to elucidate the underlying molecular mechanisms. 
   
Investigational product(s)： 
High-Bioavailability Curcumin (BCM95 curcumin) 
Development Phase：⃞ I   ▓II    ⃞III     ⃞IV    ⃞其它______   ⃞不適用 
    Study Design： 
1. ▓ Experimental Group 
□ Control Group ：  □  Placebo  
□ Study Drug  (Name、Dose、Usage)  __________________ 
□ Other _____________ 
2. Blinding：▓ Open  □ Evaluator-blind  □ Single-blind(patient)  □ Double-blind(patient+PI)    
□ Double Dummy   □ Other ______________ 
3.  Randomization:  □ Yes   ▓ No 
4. □ Parallel design   □ Crossover design   ▓ Other __single arm__   □ Not applicable 
5.  Treatment Period：5 months  □ Not applicable 
  6.  Study Period:  3 years   (or From 2026/01/01 to 2029/12/31) 
6. Dose adjustment：□ Mandatory     ▓ Selectively       □ No        □ Not applicable 
7. Study location：▓ Single □ Multi-center  □  Global 
Endpoints (Outcome measure)： 
1. Primary endpoint: 
1. Grade 3 enteritis/proctitis or grade 3 GI AE: evaluated by National Cancer Institute Common 

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Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE v. 5.0) and the criteria of the 
Radiation Therapy Oncology Group (RTOG) and European Organisation for Research and 
Treatment of Cancer (EORTC). The cumulative incidence GI symptoms (ie, abdominal pain, 
loose stools, bloody stools, tenesmus, and nausea).  
 
 
2. Secondary endpoints: 
1. Colonoscopy evaluation of proctitis by Vienna Rectoscopy Score: baseline, 2±1 weeks and 12
±1 weeks after radiation therapy completed. 
2. Any grade III adverse events during the neoadjuvant therapy: evaluated by National Cancer 
Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE v. 5.0) 
and the criteria of the Radiation Therapy Oncology Group (RTOG) and European Organisation 
for Research and Treatment of Cancer (EORTC) 
3. Clinical complete response rate of the primary tumor after completion of the neoadjuvant 
treatment: evaluated by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 
v1.1) 
4. Pathological or clinical complete response rate of the primary tumor after completion of the 
neoadjuvant treatment: defined as no residual cancer cells in the resected specimen after curative 
resection 
5. Patient’s tolerability and completion rate of the neoadjuvant therapy 
 
3.   Exploratory endpoints (if any):  
1. Three-year disease-related treatment failure rate: defined as locoregional recurrence, distal  
metastasis or cancer-related death from the neoadjuvant treatment to 3-year follow-up after  
the surgery  
2. Five-year overall survival death: defined as the death rate during the treatment and  
follow-up period 
3. Compare the molecular marker alterations in rectal tumors and adjacent tissues following 
chemoradiotherapy with those documented in existing molecular databases
Inclusion/Exclusion Criteria： 
Inclusion criteria:  
(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 
 
Exclusion criteria:  

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(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 

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requirements 
 
Study Procedures： 
This single-arm study is aimed to recruit 72 mid-to-low locally advanced rectal cancer patients 
who need neoadjuvant chemotherapy and radiotherapy. The pre-operative evaluation, including 
completed colonoscopy, neck-to-abdomen computed tomography, pelvis magnetic resonance imaging, 
and serum carcinoembryonic antigen, are arranged as a current practice guideline. After the patients 
agree to participate, a daily dose of 3g of high bioavailability curcumin is given as the chemotherapy 
starts. The curcumin therapy is continued during the whole neoadjuvant chemotherapy and radiation 
therapy. A complete blood count is checked during each cycle of chemotherapy. 
During the treatment period, participants will undergo biweekly (every 2 weeks) routine 
blood tests and adverse event assessments from the start of CRT until the completion of 
neoadjuvant therapy and subsequent surgery (approximately 3–4 months).Moreover, additional 
biochemical examinations with liver and renal function and adverse events (CTCAE version 5) and the 
criteria of the Radiation Therapy Oncology Group (RTOG) and European Organisation for Research 
and Treatment of Cancer (EORTC) are examined every 3 cycles of chemotherapy. The curcumin 
treatment is ended along with the completion of chemotherapy. An additional colonoscopy will be 
arranged 2 to 3 weeks after the radiation therapy completed to evaluate acute proctitis by Vienna 
Rectoscopy Score. After completion of the chemoradiation, colonoscopy and pelvis magnetic 
resonance imaging are conducted to evaluate the tumor response. Tumor response will be evaluated 
concurrently based on imaging and clinical findings. The total neoadjuvant CRT course lasts 
approximately 19 weeks. Based on each surgeon's clinical judgment, the patient receives either 
curative surgery or a watch-and-wait strategy. Colonoscopy and tissue biopsies of both tumor and 
adjacent normal rectal tissue will be performed at three designated time points: prior to treatment, upon 
completion of radiotherapy, and following the completion of chemoradiotherapy. The obtained 
specimens will be subjected to molecular analysis and compared with established databases to evaluate 
treatment-related molecular changes. 
For translational analyses, only residual clinical specimens (e.g., a few millimeters of surplus 
tumor tissue) obtained after standard diagnostic or therapeutic procedures will be utilized. The 
sampling volume is minimal and will not interfere with diagnostic interpretation. All specimens 
will be de-identified and coded in accordance with ethical and regulatory standards and will be 
used exclusively for translational and biomarker studies. 
Sample size calculation is performed using one proportion equality test using the exact test to 
achieving an 80% power at the 5% level of significance. With the expectation of an -15% of 
improvement of acute radiation proctitis (30% to 15%), the total estimated patients number in a single-
arm trial required is 64. Consider the patient with incomplete data and drop-out rate of 10%, the total 
estimated number of sample size is 72. Sample size calculation was performed using PASS software 
(Power Analysis and Sample Size version 2021, NCSS, Kaysville, Utah, USA).

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Concomitant Treatments：  □不適用 
1. Concomitant Therapy： 
1.1 TEGAFOX(one cycle)： 
*Oxaliplatin 85 mg/m2 in D5W 250 ml IVF 2 hrs, D1, every 2 wks 
*Tegafur-uracil 300mg/m2/day and leucovorin 90mg/day PO, given on days 1 to 5 and 8 to 12 
days, every 2 weeks 
1.2 FOLFOX(one cycle)： 
*Oxaliplatin 85 mg/m2 in D5W 250 ml IVF 2 hours, D1 
*Calcium Folinate 100 - 400 mg/m2 in D5W 250ml IVF 2 hours, D1 
*5-FU 400 mg/m2 IV bolus on D1 *5-FU (2400 mg/m2) IVF 46 hrs, Repeat every 2 weeks 
1.3 UFUR (one cycle) 
*Tegafur 300-350 mg/m2/day and leucovorin 90mg/day PO on day 1 to day 5, then rest for 2  
days for 2 weeks 
1.4 The radiation therapy modules are as follows： 
Short-Course (hypofractionated, 25 Gy/5 fractions) Radiotherapy（SCRT） 
      2. Prohibited Therapy：cell therapy, immunotherapy 
Statistical Methods： 
1. Main study Hypothesis： ■ Equality  □ Superiority  □ Non-inferiority  
   ⃞ Equivalence   □ Other  
2. Estimated Sample Size：整個試驗預計納入人數_72_，整個試驗可評估人數_64_ 
                                               本中心預計納入人數__72_，本中心可評估人數_64_ 
3. Efficacy assessment group：  ■ Intent-to-treat (ITT)   □ Per-Protocol (PP)   
                                                 □ Other ________ 
附註：意圖治療：Intent-to-treat (ITT)；依計畫書：Per-Protocol (PP)  
4. Interim analysis：  □ Yes    ■ No 
5. Statistical methods：descriptive statistics, Kaplan-Meier method, T-test 
6. Handling of Missing Data：Listwise deletion 
 
 
 

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2. Introduction and Rationale 
The primary treatment method for non-metastatic locally advanced rectal cancer is TME 
(Total mesorectal excision). In recent years, neoadjuvant chemotherapy and radiation therapy 
have been proven to decrease local recurrence and increase the possibility of organ preservation. 
[5, 6] However, radiation proctitis is a joint adverse event in one-third of patients one week 
after radiation treatment is complete;  [7] and severe acute toxicity was observed in 4.2% of 
patients. [8]  
Curcumin (diferuloylmethane) is a hydrophobic polyphenol derived from the rhizome of 
Curcuma longa. It has been proven an anti-inflammatory agent as an NF-kB inhibitor  [9] and 
has numerous intrinsic and extrinsic anti-neoplastic pathways. [10] The murine model showed 
that oral curcumin could alleviate irinotecan-induced intestinal injury via attenuation of NF‑κB 
activation, oxidative stress and endoplasmic reticulum stress. [11] One phase I clinical trial 
showed the oral form curcumin can be safe even up to 8 gram per day.[12] Moreover, the 
USFDA has designated oral curcumin as a “generally recognized as safe” agent. (US FDA; per 
21 CFR 182.10, 182.20) However, due to its hydrophobic feature, poor bioavailability limited 
its clinical application.[13]  
BCM-95® contains an extract characterized as a 95% curcuminoid complex (curcumin, 
demethoxycurcumin, and bisdemethoxycurcumin in their natural ratios) along with turmeric 
essential oil. The bioavailability of BCM-95® has been proven to be 6.93-fold compared to 
regular curcumin. [14] Therefore, the application of BCM-95® may improve radiation-related 
inflammation and chemotherapy-induced mucosal injury. Moreover, its anti-neoplastic effect 
may improve the tumor response to current neoadjuvant therapy and therefore improve the 
long-term outcome of rectal patients. 
 
2.1 Investigational product(s) 
BCM-95® curcumin 3 gram per day  
2.2 Animal and preclinical study data 
Guo et al: curcumin can promote Bax, TP53 gene, activated the caspase-3 and caspase-9 in 
CRC cell line (LoVo), which can induce cancer cell apoptosis. [15] 
Mosieniak et al.: curcumin can activate senescence and autophagy via p53 and p21 
overexpression. [16] 
 
NF-κB Ionizing radiation (IR) is well recognized for activating the transcription factor NF-
κB, a key mediator of both cancer cell resistance to treatment and radiation-induced normal 
tissue toxicity  [17]. In cancer cells, NF-κB drives the activation of pro-survival signaling 
pathways, facilitating tumor growth and progression. Additionally, NF-κB regulates the 
expression of numerous cytokines and chemokines with strong pro-inflammatory properties, 
which can exacerbate tissue injury following IR exposure [18].  
 
Curcumin has been shown to inhibit the proliferation and post-irradiation clonogenic survival 
of multiple colorectal cancer cell lines. While ionizing radiation activates NF-κB in a dose- 
and time-dependent fashion, curcumin effectively counteracts this by preventing the 
phosphorylation and degradation of IκBα, inhibiting IκB kinase activity, and reducing Akt 
phosphorylation. It also suppresses the expression of key NF-κB-regulated proteins, 
including Bcl-2, Bcl-xL, IAP-2, COX-2, and cyclin D1, thereby enhancing the therapeutic 
efficacy of radiotherapy [19].  
 

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In addition to its radiosensitizing effects, curcumin also demonstrated protective activity in 
normal intestinal cells exposed to Irinotecan. It blocked NF-κB signaling and mitigated 
Irinotecan-induced apoptosis by upregulating molecular chaperones such as GRP78, P4HB, 
and PRDX4, while downregulating pro-apoptotic proteins like CHOP and cleaved caspase-3. 
These protective effects are mediated through curcumin's inhibition of NF-κB activation, 
along with its ability to reduce oxidative stress and endoplasmic reticulum stress, ultimately 
alleviating intestinal mucosal injury caused by chemotherapy [11]. 
 
2.3 Clinical data 
Howells et al.: Curcumin is a safe and tolerable adjunct to FOLFOX chemotherapy in metastatic 
colorectal cancer patients with potential benefits of overall survival. [20] 
Carroll et al: Curcumin 4g per day can reduce 40% of aberrant crypt foci in the rectum of 
healthy smokers [21] 
 
2.4 Risks / benefits Assessment 
Benefit: the anti-inflammation and anti-neoplastic effect of curcumin may alleviate the side 
effect or improved the tumor response to neoadjuvant chemotherapy and radiation therapy. 
 
Risk: the limited case reports of curcumin on hepatitis and iron metabolism may effect 
patient with relative underlying disease such as active hepatitis or iron metabolic diseases.[1, 
22] 
 
2.5 Regulatory 
 
This study will be conducted in compliance with the protocol approved by the Institutional 
Review Board, and according to Good Clinical Practice standards.  No deviation from the 
protocol will be implemented without the prior review and approval of the IRB except where 
it may be necessary to eliminate an immediate hazard to a research subject.  In such case, the 
deviation will be reported to the IRB as soon as possible. 
3.  Objectives and Endpoints 
 
3.1 Study Objectives:  
3.1.1 Primary objective:  the anti-inflammation effect of curcumin on the radiation proctitis, 
adverse events and completion of neoadjuvant radiation therapy and chemotherapy  
3.1.2 Secondary objectives: the anti-neoplastic effect of curcumin on the treatment of rectal 
cancer in adjuvant with radiation therapy and chemotherapy 
 
3.2 Study endpoints: 
3.2.1 Primary endpoint:  
1. Grade 3 enteritis/proctitis: evaluated by National Cancer Institute Common 
Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE v. 5.0) and 
colonoscopy evaluation 2 weeks after radiation therapy completed 
 
3.2.2 Secondary endpoints:  
1. Any grade III adverse events during the neoadjuvant therapy: evaluated by National 
Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI 
CTCAE v. 5.0) 

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2. Clinical complete response rate of the primary tumor after completion of the neoadjuvant 
treatment: evaluated by Response Evaluation Criteria in Solid Tumors Version 1.1 
(RECIST v1.1) 
3. Pathological or clinical complete response rate of the primary tumor after completion of 
the neoadjuvant treatment: defined as no residual cancer cells in the resected specimen after 
curative resection 
4. Patient’s tolerability and completion rate of the neoadjuvant therapy 
4. Study Design 
 
4.1 Overall Design 
This phase II single-arm study is aimed to recruit 72 mid-to-low locally advanced rectal 
cancer patients who need neoadjuvant chemotherapy and radiotherapy. The pre-operative 
evaluation, including completed colonoscopy, neck-to-abdomen computed tomography, 
pelvis magnetic resonance imaging, and serum carcinoembryonic antigen, are arranged as a current 
practice guideline. After the patients agree to participate, a daily dose of 3g of BCM-95® curcumin 
is given as the chemotherapy starts. The curcumin therapy is continued during the whole 
neoadjuvant chemotherapy and radiation therapy. A complete blood count is checked during each 
cycle of chemotherapy. 
Moreover, additional biochemical examinations with liver and renal function and adverse 
events (CTCAE version 5) and the criteria of the Radiation Therapy Oncology Group (RTOG) and 
European Organisation for Research and Treatment of Cancer (EORTC) are examined every 3 
cycles of chemotherapy. The curcumin treatment is ended along with the completion of 
chemotherapy. An additional colonoscopy will be arranged 2 to 3 weeks after the radiation therapy 
completed to evaluate acute proctitis by Vienna Rectoscopy Score. After completion of the 
chemoradiation, colonoscopy and pelvis magnetic resonance imaging are conducted to evaluate the 
tumor response. Based on each surgeon's clinical judgment, the patient receives either curative 
surgery or a watch-and-wait strategy. 
 
Run-in Cohort (n=6) Design 
Study Design 
This trial will begin with a run-in cohort of 6 patients receiving high-bioavailability curcumin 
(BCM-95) in combination with standard neoadjuvant chemoradiotherapy (nCRT) for mid-
/low-rectal cancer. The purpose of the run-in phase is to confirm safety, tolerability, and 
feasibility prior to expanding enrollment to the full Phase II cohort. 
 
Objectives 
 
Primary Objective (Run-in cohort): 
To evaluate the incidence of dose-limiting toxicities (DLTs), particularly hepatotoxicity 
and gastrointestinal adverse events (AEs), during curcumin administration with 
concurrent chemoradiotherapy. 
 
Secondary Objectives: 
o To confirm feasibility of oral curcumin administration and patient adherence. 
o To monitor preliminary gastrointestinal protective effects (e.g., radiation 
proctitis, diarrhea). 
o To validate safety monitoring and study logistics prior to full expansion. 
 

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Patient Population 
 
6 patients with stage II–III mid-/low-rectal adenocarcinoma scheduled for standard 
nCRT will be enrolled. 
 
Patients must meet all eligibility criteria, including adequate hematologic and hepatic 
function. 
 
Treatment 
 
Investigational Product: BCM-95 curcumin, administered orally throughout the course 
of nCRT. 
 
Concomitant Therapy: Standard long-course pelvic radiotherapy (50.4 Gy/28 fractions) 
plus concurrent capecitabine. 
 
Safety Monitoring 
 
DLT Evaluation Window: Entire course of concurrent nCRT (6 weeks). 
 
DLT Criteria (adapted for this study): 
o Grade ≥3 non-hematologic toxicity (CTCAE v5.0), excluding expected alopecia 
and transient nausea/vomiting. 
o ALT or AST >3× ULN confirmed on repeat test, or ALT/AST >5× ULN at any 
time. 
o Total bilirubin >2× ULN with concurrent ALT/AST elevation. 
o Grade 4 hematologic toxicity lasting >7 days. 
o Any toxicity requiring treatment interruption >2 weeks. 
 
Monitoring Plan: 
o CBC, renal, and liver function tests weekly during nCRT. 
o Symptom assessment (diarrhea, proctitis, fatigue) using CTCAE v5.0 and RTOG 
scoring. 
 
Decision Rules 
 
If ≤1 of 6 patients develops a DLT, the study will proceed to Phase II enrollment 
(planned n=72). 
 
If ≥2 of 6 patients develop a DLT, the Principal Investigator (PI)  and Co-Principal 
Investigator (Co-PI) will review safety data, and dose adjustment, protocol amendment, 
or early termination will be considered before further enrollment. 
 
Transition to Full Cohort 
 
Upon the confirmation of safety and IRB notification, the trial will expand to the Phase 
II cohort. 
 
The same treatment regimen will be maintained unless other safety issues come into 
concern. 
 
 
 
Flow Chart (試驗流程圖)： 

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14 
 
4.2 
Number of Patients 
 
Sample size calculation is performed using one proportion equality test using 
the exact test to achieving an 80% power at the 5% level of significance. With 
the expectation of an -15% of improvement of acute radiation proctitis (30% 
to 15%), the total estimated patients number in a single-arm trial required is 
64. Consider the patient with incomplete data and drop-out rate of 10%, the 
total estimated number of sample size is 72. Sample size calculation was 
performed using PASS software (Power Analysis and Sample Size version 
2021, NCSS, Kaysville, Utah, USA). 
4.3 
Schedule of Activities 
 
Time-Event scheme(評估時程表): 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
15 
 
Immune profiling 
 
 Peripheral blood 
 
The presence of tumors is often linked to a significant reduction in both effector and 
memory T cell populations, a shift from type 1 to type 2 immune responses, and 
diminished effector T cell proliferation. Preclinical studies have shown that curcumin can 
counteract these immunosuppressive effects by preserving T cell populations, expanding 
central memory (TCM) and effector memory (TEM) T cell subsets, reversing the type 2 
immune bias, and restoring T cell proliferation in tumor-bearing hosts. Curcumin also 
suppresses regulatory T cell (Treg) function by downregulating the secretion of 
immunosuppressive cytokines such as TGF-β and IL-10. Importantly, it enhances the 
cytotoxic activity of effector T cells against cancer cells. These findings highlight 
curcumin’s potential as an immunomodulatory agent capable of mitigating tumor-induced 
suppression of cell-mediated immunity and augmenting antitumor immune responses [23]. 
To determine whether these findings are applicable to patients, we plan to use BD 
FACSymphony high-parameter flow cytometry to assess T effector cell function before 
and after combinatorial treatment. This will be done using a validated antibody panel 
available at Chang Gung Memorial Hospital (Table 1). 
 
Table 1. Tentative antibody panel for BD FACSymphony high-parameter 
immunophenotyping. (The antibody panel is subject to modification based on the 
experimental conditions.) 
 
To evaluate whether curcumin can suppress pro-inflammatory cytokines during 
radiotherapy and chemotherapy, we plan to employ a cytokine array to comprehensively 
assess cytokine levels before and after total neoadjuvant treatment. Additionally, we aim to 
monitor circulating tumor DNA (ctDNA) dynamics—a promising non-invasive 

 
16 
 
biomarker—by measuring ctDNA levels pre- and post-treatment. This approach will allow 
us to explore potential correlations between ctDNA fluctuations and treatment response or 
clinical outcomes, supporting the use of liquid biopsy for real-time monitoring and 
assessment of therapeutic efficacy. As a control group, we will include blood samples from 
patients with chronic liver disease but without HCC, collected from the Human Tissue Bio-
bank at Chang Gung Memorial Hospital. 
 
*We will use the Milliplex cytokine array (Human Cytokine/Chemokine Magnetic Bead 
Panel IV; Catalog #HCYP4MAG-64K), which includes targets such as BAFF, Blys, 
BRAK, CXCL14, CCL28, CXCL16, HCC-4, CCL16, HMGB1, IFNβ, IL-14, IL-19, IL-24, 
IL-28B, IL-32α, IL-34, IL-35, IL-36β, IL-1F8, IL-37, IL-1F7, IL-38, IL-1F10, MIP-4, 
MPIF-1, CCL23, and YKL40. 
(Note: The panel may be adjusted depending on experimental needs.) 
 
 Tumor biopsy  
 
To investigate whether curcumin enhances the antitumor efficacy and mitigates normal 
tissue toxicity of radiotherapy and chemotherapy, we will employ multiplex 
immunohistochemistry to perform high-dimensional spatial profiling of both tumor and 
adjacent normal colon mucosal tissues from colorectal cancer (CRC) patients. This cutting-
edge multiplex imaging technique allows for simultaneous detection of dozens of protein 
markers on formalin-fixed paraffin-embedded (FFPE) samples, preserving spatial context 
and cellular interactions within the tumor microenvironment [24]. 
 
Using multiplex immunohistochemistry, we will comprehensively characterize immune 
cell infiltration patterns, including CD4+ and CD8+ T cells, regulatory T cells (Tregs), 
macrophages (M1 and M2 phenotypes), and dendritic cells, as well as assess expression 
levels of immune checkpoint molecules such as PD-1, PD-L1, CTLA-4, and CD47 on both 
immune and tumor cells. We will also evaluate stromal components, cytokine-associated 
markers, and markers of tissue damage or repair to assess treatment-induced changes in 
both tumor and normal mucosa. By comparing immune cell composition, activation states, 
and checkpoint expression in tissues from curcumin-treated versus untreated cohorts, we 
aim to delineate how curcumin modulates the immunological landscape of CRC. This will 
help determine whether curcumin not only amplifies local and systemic antitumor 
immunity but also confers a protective effect against treatment-induced inflammation and 
injury in adjacent normal tissues [25]. 
 
5. Study Population 
 
5.1 Inclusion Criteria 
         
Teeatment group 
Inclusion criteria: 
(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. 

 
17 
 
(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 
 
5.2 Exclusion Criteria 
 
       Treatment group 
Exclusion criteria: 
(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…etc. 
(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 < 

 
18 
 
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 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 
 
 
5.3 Withdrawal criteria 
Subject should be withdrawn from the study due to any of the following conditions: 
1. The subject voluntarily decides to withdraw her/his consent 
2. The subject dies or is lost to follow-up 
3. The subject is pregnancy 
4. The subject develops disease progression (metastasis or enlargement confirmed) 
5. Any clinical adverse event, laboratory abnormality, intercurrent illness, or any occurrence or 
change in the subject’s physically and/or psychologically status giving indication to the 
investigator that further participation in the study may not be the best interest of the subject 
6. The subject does not receive, or is unable to receive, the study intervention, does not keep 
appointments, or otherwise does not adhere to protocol requirements 
7. The subject was enrolled by error and/or it is discovered that the subject does not meet the 
eligibility criteria after enrollment 
8. The study is terminated prematurely by the investigator, research institution, sponsor, IRB or 
regulatory authorities 
For a subject who is withdrawn due to progress confirmed, CT (or MRI) and colonoscopy could be 
waived at the Early Termination Visit per the investigator’s judgments. If a subject is discontinued 
due to an AE, every effort will be made to follow the event until event resolves or stabilizes at a 
level acceptable to the investigator. 
 
6. Treatments 
 
6.1.Treatment Administration 
       A daily dose or high bioavailability curcumin (BCM-95 curcumin) 3g per day is given orally 
along with the neoadjuvant short-course radiation therapy and chemotherapy. 
6.2. Concomitant Therapy 
1. Concomitant Therapy： 
  
1.1 TEGAFOX(one cycle)： 
*Oxaliplatin (own expense) 85 mg/m2 in D5W 250 ml IVF 2 hrs, D1, every 2 wks 
*Tegafur-uracil 300mg/m2/day and leucovorin 90mg/day, given on days 1 to 5 and 8 to 12 
days, every 2 weeks 
1.2 FOLFOX(one cycle)： 

 
19 
 
*Oxaliplatin (own expense) 85 mg/m2 in D5W 250 ml IVF 2 hours, D1 
*Calcium Folinate 100 - 400 mg/m2 in D5W 250ml IVF 2 hours, D1 
*5-FU 400 mg/m2 IV bolus on D1 *5-FU (2400 mg/m2) IVF 46 hrs, Repeat every 2 weeks 
1.3 UFUR (one cycle) 
*Tegafur 300-350 mg/m2/day and leucovorin 90mg/day PO on day 1 to day 5, then rest for  
2  days for 2 weeks 
1.4 The radiation therapy modules are as follows： 
Short-Course (hypofractionated, 25 Gy/5 fractions) Radiotherapy (SCRT) 
2. Prohibited Therapy：cell therapy, immunotherapy 
       
7. Efficacy Assessments 
 
1. Grade 3 enteritis/proctitis: evaluated by National Cancer Institute Common 
Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE v. 5.0) and the criteria 
of the Radiation Therapy Oncology Group (RTOG) and European Organization for 
Research and Treatment of Cancer (EORTC). The sign or symptoms of radiation proctitis 
(diarrhea, rectal bleeding, rectal pain) is evaluated and recorded by our research nurse 2 to 4 
weeks after radiation therapy completed. Colonoscopy evaluation for Vienna Rectoscopy 
Score will take place 2 to 3 weeks after the radiation therapy is completed. 
 
2. Any grade III adverse events during the neoadjuvant therapy: evaluated by clinicans 
according to National Cancer Institute Common Terminology Criteria for Adverse Events 
Version 5.0 (NCI CTCAE v. 5.0) every cycles of chemotherapy. An additional evaluation 
and record will be recorded by the research nurse every 3 cycles of chemotherapy. 
 
3. Clinical complete response rate of the primary tumor after completion of the neoadjuvant 
treatment: evaluated by Response Evaluation Criteria in Solid Tumors Version 1.1 
(RECIST v1.1) after neoadjuvant chemotherapy and radiation therapy completed 
 
4. Pathological or clinical complete response rate of the primary tumor after completion of 
the neoadjuvant treatment: defined as no residual cancer cells in the resected specimen after 
curative resection 
 
5. Patient’s tolerability and completion rate of the neoadjuvant therapy 
 
 
8. Safety Assessments 
 
The complete blood count is evaluated on each admission for chemotherapy. The adverse 
events is evaluated according to National Cancer Institute Common Terminology Criteria for 
Adverse Events Version 5.0 (NCI CTCAE v. 5.0). Serum creatinine, electrolyte, AST, ALT, 
total and direct bilirubin is examined on each 3 cycle of chemotherapy.  
 If ALT or AST exceeds three times the upper limit of normal (3×ULN), curcumin 
administration will be suspended. This 3×ULN threshold is a commonly used warning 
indicator for drug-induced liver injury. In such cases, we will monitor liver function tests 
weekly until the values recover to <1.5×ULN or return to baseline. 
 
 

 
20 
 
9. Adverse event reporting 
Dr. Shu-Huan Huang will report SAEs to the IRB of Chang Gung Medical Foundation 
according to the Serious Adverse Event Reporting Procedures and Guidelines as posted in 
the Clinical Trials Resource on the website of Chang Gung Medical Foundation IRB. SAE 
reports to the IRB should include the following information when calling the Medical 
Monitor: 
 Date and time of the SAE 
 Date and time of the SAE report 
 Name of reporter 
 Call back phone number 
 Affiliation/Institution conducting the study 
 Protocol number 
 Title of protocol 
 Description of the SAE, including attribution to drug and expectedness    
 
9.1 Definitions and reports of Adverse Events 
All adverse events that occur after the informed consent is signed (including run-in) must be 
recorded on the adverse event CRF (paper and/or electronic) whether or not related to study 
agent. AE Data Elements including: 
 AE reported date 
 AE Verbatim Term 
 CTCAE Term (v 5.0) 
 Event onset date and event ended date 
 Severity grade 
 Attribution to study agent (relatedness) 
 Whether or not the event was reported as a Serious Adverse Event (SAE) 
 Action taken with the study agent 
 Outcome of the event 
 Comments 
 
Identify the adverse event using the NCI Common Terminology Criteria for Adverse Events 
(CTCAE) version 5.0.  The CTCAE provides descriptive terminology and a grading scale for 
each adverse event listed. 
 
AEs will be assessed according to the CTCAE grade associated with the AE term.  AEs that 
do not have a corresponding CTCAE term will be assessed according to their impact on the 
participant’s ability to perform daily activities as follows: 
 
 
Grade 
Severity 
Description  
1 
Mild 
 
Barely noticeable, does not influence functioning 

Causing no limitations of usual activities
2 
Moderate 
 
Makes participant uncomfortable, influences functioning
 
Causing some limitations of usual activities
3 
Severe 
 
Severe discomfort, treatment needed 
 
Severe and undesirable, causing inability to carry out 
usual activities
4 
Life threatening 
 
Immediate risk of death 
 
Life threatening or disabling

 
21 
 
5 
Fatal 
 
Causes death of the participant 
 
The possibility that the adverse event is related to study drug will be classified as one of the 
following:  not related, unlikely, possible, probable, definite. 
  
DEFINITION of Serious Adverse Events: ICH Guideline E2A and GCP of Taiwan define 
serious adverse events as those events, occurring at any dose, which meet any of the 
following criteria: 
 Results in death 
 Is life threatening (Note: the term life-threatening refers to an event in which the 
patient was at risk of death at the time of the event; it does not refer to an event 
which hypothetically might have caused death if it were more severe). 
 Requires inpatient hospitalization or prolongation of existing hospitalization 
 Results in persistent or significant disability/incapacity 
 Is a congenital abnormality/birth defect 
 Events that may not meet these criteria, but which the investigator finds very 
unusual and/or potentially serious, will also be reported in the same manner. 
 
9.2 Adverse event follow-up 
All AEs, including lab abnormalities that in the opinion of the investigator are clinically 
significant, will be followed according to good medical practices and documented as such. 
Site staff should send follow-up reports as requested when additional information is 
available.  Additional information should be entered on the IRB of Chang Gung Medical 
Foundation of SAE form in the appropriate format.  Follow-up information should be sent to 
Chang Gung Medical Foundation IRB as soon as possible according to IRB’s Serious 
Adverse Event Reporting Procedures and Guidelines.  
 
10. Criteria for the termination of the trial 
 
1. The drug’s lack of efficacy is proven early for failure to obtain the expected benefit. 
Treatment does not lead to an equal or better result than the treatment against which is 
compared. 
2. Be shown prematurely that the drug is harmful, resulting in a risk for patients enrolled in 
the trial. 
3. Logistics issues for being unable to recruit the expected number of subjects. It is 
important to publish this type of trial indicating problems observed and the causes leading 
to early termination since they can help other investigators avoid the same problems and 
repeating the same mistakes. 
11. Statistical Considerations 
 
Quantitative variables will be presented as mean±standard deviation (SD) and categorical 
variables will be presented as proportions. The Student t-test, Mann-Whitney U-test and 
Spearman rank correlation test will be used to analyze differences between groups of 
variables.  
 
11.1 Sample size Determination 
Sample size calculation is performed using one proportion equality test using the exact test 
to achieving an 80% power at the 5% level of significance. With the expectation of an -15% 

 
22 
 
of improvement of acute radiation proctitis (30% to 15%), the total estimated patients 
number in a single-arm trial required is 64. Consider the patient with incomplete data and 
drop-out rate of 10%, the total estimated number of sample size is 72. Sample size 
calculation was performed using PASS software (Power Analysis and Sample Size version 
2021, NCSS, Kaysville, Utah, USA). 
 
11.2 Planned Statistical methods of analysis 
Categorical variables were compared using Pearson’s chi-squared test or Fisher’s exact test, 
while continuous variables were compared using the Mann–Whitey U test. Survival curves 
were generated using the Kaplan–Meier method and compared between the two groups 
using the log-rank test. The index date of survival analysis was the day the patient started 
radiotherapy. All statistical analyses were performed using the Statistical Package for 
Social Sciences (SPSS), version 24 (IBM Corp., New York, NY, USA). Differences were 
considered statistically significant at a two-sided p-value of < 0.05. 
 
11.2.1 Efficacy analysis 
 
 
Adverse events are assessed by the clinician on each cycle of admission, and additional 
record of adverse events (CTCAE version 5) by our research nurse on every 3 cycles of 
chemotherapy. 
Clinical complete remission is evaluated on each colonoscopy examination after the 
neoadjuvant chemotherapy and radiation therapy completed according to Response 
Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1). In addition, the 
pathologist evaluates pathological complete response and tumor regression grade after 
curative resection.  
 
11.2.2 Safety analysis 
The adverse events and complete blood count is evaluated on each admission for 
chemotherapy. Serum creatinine, electrolyte, AST, ALT, total and direct bilirubin is 
examined on each 3 cycle of chemotherapy. Adverse events are assessed by the clinician on 
each cycle of admission, and additional evaluation of adverse events (CTCAE version 5) by 
our research nurse on every 3 cycles of chemotherapy, which is the standard follow-up 
scheduled of the chemotherapy.  
 
11.2.3 Additional analysis 
 
Not applicable 
 
11.2.4 The level of significance 
A p-value less than 0.05 was considered significant and was denoted by *. 
 
11.2.5 Analysis Population 
 
The outcome of this single arm clinical trial is compared with other clinical trials and our 
previous retrospective neoadjuvant chemoradiation data of CGMH. 
 
11.2.5.1 Procedure for accounting for missing, unused and spurious data 
The incomplete clinical data and sequencing data with poor quality will be excluded in 
the study. 

 
23 
 
 
11.2.5.2 Procedures for reporting any deviation(s) from the original statistical 
plan 
Investigators permit IRB to access to the raw data of experiment for trial-related 
monitoring, audits and regulatory inspection if additional statistical plan is required. 
 
12. Direct access to source data/documents 
Investigators permit IRB to access to the source data of experiment for trial-related 
monitoring, audits and regulatory inspection. 
 
13. Ethical considerations 
           
This study will be conducted according to Taiwan and international standards of Good 
Clinical Practice for all studies.  Applicable government regulations and Chang Gung 
Medical Foundation research policies and procedures will also be followed. 
 
This protocol and any amendments will be submitted to the Chang Gung Medical Foundation 
Institutional Review Board (IRB) for formal approval to conduct the study.  The decision of 
the IRB concerning the conduct of the study will be made in writing to the investigator.   
 
All subjects for this study will be provided a consent form describing this study and 
providing sufficient information for subjects to make an informed decision about their 
participation in this study.  This consent form will be submitted with the protocol for review 
and approval by the IRB.  The formal consent of a subject, using the IRB-approved consent 
form, will be obtained before that subject is submitted to any study procedure.  This consent 
form must be signed by the subject or legally acceptable surrogate, and the investigator-
designated research professional obtaining the consent.  
 
14. Data handling and keeping 
Clinical samples will be collected in Chang Gung Medical Foundation. The sequencing 
data will be stored in computers of laboratory with an electronic encryption. The clinical 
and source data can only be assessed by clinical doctors and investigators of the study. 
Data and Safety Monitoring Plan (DSMP) 
This section outlines the Data and Safety Monitoring Plan (DSMP) for the clinical study. 
The purpose of the DSMP is to ensure the safety of study participants and the integrity of 
the study data. The monitoring activities will be performed regularly and will be adapted 
based on study progress and emerging safety signals. 
1. Monitoring Plan 
- Enrollment monitoring will be conducted tri-monthly by the Principal Investigator (PI). 
- Serious Adverse Events (SAEs) will be reported immediately and reviewed quarterly by 
the Safety Officer. 
- Protocol deviations will be recorded and reviewed monthly by the Clinical Research 
Coordinator (CRC). 
- Data quality will be assessed on an ongoing basis by the Data Manager. 
2. Reporting 

 
24 
 
All safety monitoring activities and findings will be reported to the Sponsor and PI. 
 
 
15.  Financing and Insurance 
       
      This study is supported by Chang Gung Medical Foundation (CGMF). The main research 
fund is aimed to be supported by Chang Gung Medical Foundation. 
 
16.  Privacy and Confidentiality Protection 
A research code will be used to represent the patient’s identity, and this code will not display 
the patient’s name, ID number, or address. The principal investigator will maintain a strict 
confidentiality stance regarding the results and diagnoses of the patient’s visit. If research 
findings are published, the patient’s identity will still be kept confidential. 
By signing the consent form, the patient is agree that his or her visit records may be directly 
reviewed by monitors, auditors, research ethics committees, and regulatory authorities to 
ensure that the research process and data comply with relevant laws and regulations. The 
individuals mentioned above also pledge never to violate the confidentiality of the patient’s 
identity. 
According to the regulations of the United States or the European Union for pharmaceutical 
management, trial results will be published on the public clinical trial information website: 
Clinicaltrials.gov (for the United States). However, the patient’s personal information will 
remain confidential, and the website will only have a summary of the trial results. 
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Imam, Z., et al., Drug induced liver injury attributed to a curcumin supplement. Case 
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