Chidamide + Celecoxib in Advanced Metastatic Colorectal Cancer (CCmCC)

NCT ID: NCT05281276

Last Updated: 2024-12-20

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE1

Total Enrollment

9 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-09-20

Study Completion Date

2024-03-26

Brief Summary

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This study is designed as an open-label, dose-escalation manner to determine the MFD of chidamide in combination with celecoxib in patients with advanced mCRC.

Detailed Description

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This is a monocentric, open-label, non-randomized dose feasibility study trial to characterize the safety, tolerability, pharmacokinetics, and preliminary efficacy of chidamide in combination with celecoxib in patients with advanced mCRC. Each cohort will have up to 6 subjects. Eligible patients will be assigned to 1 of up to 2 sequential cohorts. The planned dose levels of the two cohorts include (1) 20 mg chidamide plus 200 mg celecoxib; and (2) 30 mg chidamide plus 200 mg celecoxib.

For each subject, the treatment period is divided into two periods, a run-in period and a combination therapy period.

Conditions

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Metastatic Colorectal Cancer

Keywords

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Metastatic Colorectal Cancer

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

Cohort1: Chidamide(20mg)+Celecoxib(200mg); Cohort2: Chidamide(30mg)+Celecoxib(200mg)
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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chidamide (20 mg) BIW in combination with celecoxib (CC)

Chidamide: The dosing schedule is four/six tablets (20 mg) BIW, taken at 30 min after breakfast. The interval between two doses in each week should not be less than 3 days.

Celecoxib: The dosing schedule is one capsule (200 mg) daily taken at 30 min after breakfast.

A treatment cycle is defined as a period of 4 weeks (28 days)

Group Type EXPERIMENTAL

chidamide

Intervention Type DRUG

During the run-in period, the patients will take a single dose of chidamide on Day 3. In a 28-day treatment cycle, the dosing schedule is four/six table (20/30mg) BIW .

celecoxib

Intervention Type DRUG

During the run-in period, the patients will take a single dose of celecoxib on Day 1. In a treatment cycle, the dosing schedule is one capsule(200 mg) daily.

chidamide(30 mg) BIW in combination with celecoxib (CC)

Chidamide: The dosing schedule is four/six tablets (30 mg) BIW, taken at 30 min after breakfast. The interval between two doses in each week should not be less than 3 days.

Celecoxib: The dosing schedule is one capsule (200 mg) daily taken at 30 min after breakfast.

A treatment cycle is defined as a period of 4 weeks (28 days)

Group Type EXPERIMENTAL

chidamide

Intervention Type DRUG

During the run-in period, the patients will take a single dose of chidamide on Day 3. In a 28-day treatment cycle, the dosing schedule is four/six table (20/30mg) BIW .

celecoxib

Intervention Type DRUG

During the run-in period, the patients will take a single dose of celecoxib on Day 1. In a treatment cycle, the dosing schedule is one capsule(200 mg) daily.

Interventions

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chidamide

During the run-in period, the patients will take a single dose of chidamide on Day 3. In a 28-day treatment cycle, the dosing schedule is four/six table (20/30mg) BIW .

Intervention Type DRUG

celecoxib

During the run-in period, the patients will take a single dose of celecoxib on Day 1. In a treatment cycle, the dosing schedule is one capsule(200 mg) daily.

Intervention Type DRUG

Other Intervention Names

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tucidinostat HBI-8000 Celebrex

Eligibility Criteria

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Inclusion Criteria

1. The patient is 20-year-old or older on the day that consent is provided.
2. With histologically or cytologically proven metastatic colorectal adenocarcinoma.
3. Have measurable lesions according to RECIST v1.1.
4. Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0 to 2.
5. Adequate organ function as defined below:

i. White blood cells (WBC) ≥3,000/μL ii. Absolute neutrophil count ≥1,500/μL iii. Platelets ≥1 x 105/μL iv. Hemoglobin ≥9.0 g/dL v. Total bilirubin ≤1.5 x the upper limit of normal (ULN) vi. AST(SGOT)/ALT(SGPT) ≤3 x ULN (or ≤5 x ULN if liver metastases are present) vii. Serum creatinine ≤1.5 x ULN
6. Patients who had received or were intolerant of at least 2 front-line systemic treatments. In addition, patients have failed or refused all available standard treatment, or were intolerant of such treatments. For K-ras wild type tumor, anti-EGFR therapy must have been done. For K-ras mutant tumor, antiangiogenic therapy must have been done.
7. Able to take oral medication.
8. With a life expectancy of at least 3 months.
9. Female patients of childbearing potential must have a negative urine or serum pregnancy test.
10. Patients in reproductive age must be willing to use adequate contraception (refer to Section 8.4.2 of the protocol for adequate contraception methods) during the study and 3 months after the end of the study.
11. Ability to understand and the willingness to provide a written informed consent document.


1. The patient is 20-year-old or older on the day that consent is provided.
2. With histologically or cytologically proven metastatic colorectal adenocarcinoma.
3. Have measurable lesions according to RECIST v1.1.
4. Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0 to 2.
5. Adequate organ function as defined below:

i. White blood cells (WBC) ≥3,000/μL ii. Absolute neutrophil count ≥1,500/μL iii. Platelets ≥1 x 105/μL iv. Hemoglobin ≥9.0 g/dL v. Total bilirubin ≤1.5 x the upper limit of normal (ULN) vi. AST(SGOT)/ALT(SGPT) ≤3 x ULN (or ≤5 x ULN if liver metastases are present) vii. Serum creatinine ≤1.5 x ULN
6. Patients who had received or were intolerant of at least 2 front-line systemic treatments. In addition, patients have failed or refused all available standard treatment, or were intolerant of such treatments. For K-ras wild type tumor, anti-EGFR therapy must have been done. For K-ras mutant tumor, antiangiogenic therapy must have been done.
7. Able to take oral medication.
8. With a life expectancy of at least 3 months.
9. Female patients of childbearing potential must have a negative urine or serum pregnancy test.
10. Patients in reproductive age must be willing to use adequate contraception (refer to Section 8.4.2 of the protocol for adequate contraception methods) during the study and 3 months after the end of the study.
11. Ability to understand and the willingness to provide a written informed consent document.

Exclusion Criteria

1. With known central nervous system (CNS) metastases, a history of CNS metastases or leptomeningeal diseases.
2. With known hypersensitivity towards chidamide, celecoxib, sulfonamides, aspirin, NSAIDs, or any other agents used in the study, including the excipient in the study agent; or with history of asthma, urticarial, or other allergic-type reactions after taking aspirin or other NSAIDs.
3. With severe systemic disease, such as renal disease (serum creatinine \>1.5 x ULN), liver disease (AST/ALT \>3 x ULN, AST/ALT \>5 x ULN if metastatic liver disease were known), active gastrointestinal hemorrhage or increased risks of gastrointestinal bleeding, uncontrolled diabetes, or uncontrolled hypertension.
4. With uncontrolled or significant cardiovascular diseases, including:

i. Symptomatic congestive heart failure within 6 months prior to screening, or left ventricular ejection fraction \<50% prior to screening ii. Myocardial infarction within 12 months prior to screening iii. Severe or unstable angina within 6 months prior to screening iv. History of any significant ventricular arrhythmias (e.g., ventricular tachycardia, ventricular fibrillation, or TdP) v. History of significant QT interval prolongation, or corrected QT interval (QTc) \>450 ms prior to screening vi. History of cerebrovascular accident vii. Symptomatic coronary heart disease requiring treatment with agents
5. With the size of fluid area detected by cardiac ultrasonography in cavum pericardium ≥ 10 mm.
6. With history of organ transplantation.
7. With known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness.
8. With autoimmune disorders or history of organ transplantation who require immunosuppressive therapy.
9. Has had prior chemotherapy, targeted small molecule therapy, radiation therapy, or any NSAID within 2 weeks prior to the first dose of study medication or who has not recovered from adverse events to CTCAE v5.0 Grade 1 due to a previously administered agent.
10. Has clinical significant gastrointestinal abnormality, e.g., unable to swallow, chronic diarrhea, ileus, or bowel obstruction, which would interfere the ingestion, transportation, or absorption of oral agents.
11. With active infection \[suffered from active infection of bacteria, virus, fungi, mycobacteria, parasites, or other infections (excluding nail bed fungal infections), or require intravenous antibiotic therapy, or antiviral therapy, or hospitalization due to any significant infection events within 4 weeks\], or persistent fever within 14 days prior to study entry.
12. Had major surgery \<6 weeks prior to study entry.
13. Has known psychiatric disorder, mental deficiency, or substance abuse disorder that would limit compliance with study requirements.
14. Is currently participating and receiving study therapy, or has participated in a study of an investigational agent and received study therapy or used an investigation device within 4 weeks of the first dose of study medication.
15. Pregnant or lactating female.
16. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might interfere the results of the trial or is not in the best interest of the subject to participate, in the opinion of the investigator.
Minimum Eligible Age

20 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Taipei Medical University Shuang Ho Hospital

OTHER

Sponsor Role lead

Responsible Party

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Chao Tsu-Yi

Director, Cancer Center

Responsibility Role PRINCIPAL_INVESTIGATOR

Locations

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Taipei Medical University Shuang Ho Hospital

New Taipei City, , Taiwan

Site Status

Countries

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Taiwan

Other Identifiers

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N202007026

Identifier Type: -

Identifier Source: org_study_id