Chidamide + Celecoxib in Advanced Metastatic Colorectal Cancer (CCmCC)

NCT05281276 | Terminated Phase 1

• 1 other identifier: N202007026
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Metastatic Colorectal Cancer

Keywords

Metastatic Colorectal Cancer

Outcome Measures

Primary Outcomes (13)

• Maximum Feasible Dose (MFD)

  Maximum Feasible Dose (MFD): is defined as the highest dose for which ≤1 of 6 evaluable subjects experiencing DLT during the first treatment cycle (28 days) of the combination therapy. If the dose of Cohort 1 is not tolerable by ≥2 evaluable subjects, the MFD will be considered as not determined.

  defined as the highest dose for which ≤1 of 6 evaluable subjects experiencing DLT during the first treatment cycle (28 days) of the combination therapy, assessed up to 24 months

• Pharmacokinetics profiles-(AUC0-t)

  Area under the plasma concentration-time curve from time zero to time t(AUC0-t)

  Run-in period, on day1, blood sample will be 0, 1, 2, 6, 12, and 24 hours; on day3, blood sample will be 0, 1, 2, 6, 12, 24, 48, and 72 hours.Combination therapy period, on day1 & day25, blood sample will be 0, 1, 2, 6, 12, 24, 48 and 72 hours.

• Pharmacokinetics profiles-(AUC0-∞)

  Area under the plasma concentration-time curve from time zero to infinity(AUC0-∞)

  Run-in period, on day1, blood sample will be 0, 1, 2, 6, 12, and 24 hours; on day3, blood sample will be 0, 1, 2, 6, 12, 24, 48, and 72 hours.Combination therapy period, on day1 & day25, blood sample will be 0, 1, 2, 6, 12, 24, 48 and 72 hours.

• Pharmacokinetics profiles-(Cmax)

  Maximum plasma concentration(Cmax)

  Run-in period, on day1, blood sample will be 0, 1, 2, 6, 12, and 24 hours; on day3, blood sample will be 0, 1, 2, 6, 12, 24, 48, and 72 hours.Combination therapy period, on day1 & day25, blood sample will be 0, 1, 2, 6, 12, 24, 48 and 72 hours.

• Pharmacokinetics profiles-(Tmax)

  Time to maximum plasma concentration(Tmax)

  Run-in period, on day1, blood sample will be 0, 1, 2, 6, 12, and 24 hours; on day3, blood sample will be 0, 1, 2, 6, 12, 24, 48, and 72 hours.Combination therapy period, on day1 & day25, blood sample will be 0, 1, 2, 6, 12, 24, 48 and 72 hours.

• Pharmacokinetics profiles-(T1/2)

  Half-life(T1/2)

  Run-in period, on day1, blood sample will be 0, 1, 2, 6, 12, and 24 hours; on day3, blood sample will be 0, 1, 2, 6, 12, 24, 48, and 72 hours.Combination therapy period, on day1 & day25, blood sample will be 0, 1, 2, 6, 12, 24, 48 and 72 hours.

• Pharmacokinetics profiles-(Kel)

  Elimination rate constant(Kel)

  Run-in period, on day1, blood sample will be 0, 1, 2, 6, 12, and 24 hours; on day3, blood sample will be 0, 1, 2, 6, 12, 24, 48, and 72 hours.Combination therapy period, on day1 & day25, blood sample will be 0, 1, 2, 6, 12, 24, 48 and 72 hours.

• Pharmacokinetics profiles-(AUC0-τ,ss)

  Area under the plasma concentration-time curve from time zero to time τ (dosing interval) at steady state(AUC0-τ,ss)

  Run-in period, on day1, blood sample will be 0, 1, 2, 6, 12, and 24 hours; on day3, blood sample will be 0, 1, 2, 6, 12, 24, 48, and 72 hours.Combination therapy period, on day1 & day25, blood sample will be 0, 1, 2, 6, 12, 24, 48 and 72 hours.

• Pharmacokinetics profiles-(Cave,ss)

  Average plasma concentration at steady state(Cave,ss)

  Run-in period, on day1, blood sample will be 0, 1, 2, 6, 12, and 24 hours; on day3, blood sample will be 0, 1, 2, 6, 12, 24, 48, and 72 hours.Combination therapy period, on day1 & day25, blood sample will be 0, 1, 2, 6, 12, 24, 48 and 72 hours.

• Pharmacokinetics profiles-(Cmin,ss)

  Minimum (trough) plasma concentration at steady state(Cmin,ss)

  Run-in period, on day1, blood sample will be 0, 1, 2, 6, 12, and 24 hours; on day3, blood sample will be 0, 1, 2, 6, 12, 24, 48, and 72 hours.Combination therapy period, on day1 & day25, blood sample will be 0, 1, 2, 6, 12, 24, 48 and 72 hours.

• Pharmacokinetics profiles-(Cmax,ss)

  Maximum (peak) plasma concentration at steady state(Cmax,ss)

  Run-in period, on day1, blood sample will be 0, 1, 2, 6, 12, and 24 hours; on day3, blood sample will be 0, 1, 2, 6, 12, 24, 48, and 72 hours.Combination therapy period, on day1 & day25, blood sample will be 0, 1, 2, 6, 12, 24, 48 and 72 hours.

• Pharmacokinetics profiles-(Tmax,ss)

  Time to maximum plasma concentration at steady state(Tmax,ss)

  Run-in period, on day1, blood sample will be 0, 1, 2, 6, 12, and 24 hours; on day3, blood sample will be 0, 1, 2, 6, 12, 24, 48, and 72 hours.Combination therapy period, on day1 & day25, blood sample will be 0, 1, 2, 6, 12, 24, 48 and 72 hours.

• Pharmacokinetics profiles-(DF)

  Degree of fluctuation(DF)

  Run-in period, on day1, blood sample will be 0, 1, 2, 6, 12, and 24 hours; on day3, blood sample will be 0, 1, 2, 6, 12, 24, 48, and 72 hours.Combination therapy period, on day1 & day25, blood sample will be 0, 1, 2, 6, 12, 24, 48 and 72 hours.

Secondary Outcomes (2)

• Progression-free survival

  from the time of first day of dosing (Run-in period Day1) until the date of first objective disease progression or death, assessed up to 24 months

• Objective response

  From enrollment until disease progression or unacceptable toxicity, assessed up to 24 months

Study Arms (2)

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

EXPERIMENTAL

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)

Drug: chidamide; Drug: celecoxib

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

EXPERIMENTAL

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)

Drug: chidamide; Drug: celecoxib

Interventions

chidamide 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 .

Also known as: tucidinostat, HBI-8000

chidamide (20 mg) BIW in combination with celecoxib (CC); chidamide(30 mg) BIW in combination with celecoxib (CC)

celecoxib 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.

Also known as: Celebrex

chidamide (20 mg) BIW in combination with celecoxib (CC); chidamide(30 mg) BIW in combination with celecoxib (CC)

Eligibility Criteria

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

You may qualify if:

• The patient is 20-year-old or older on the day that consent is provided.
• With histologically or cytologically proven metastatic colorectal adenocarcinoma.
• Have measurable lesions according to RECIST v1.1.
• Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0 to 2.
• 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
• 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.
• Able to take oral medication.
• With a life expectancy of at least 3 months.
• Female patients of childbearing potential must have a negative urine or serum pregnancy test.
• 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.
• Ability to understand and the willingness to provide a written informed consent document.

You may not qualify if:

• The patient is 20-year-old or older on the day that consent is provided.
• With histologically or cytologically proven metastatic colorectal adenocarcinoma.
• Have measurable lesions according to RECIST v1.1.
• Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0 to 2.
• 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
• 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.
• Able to take oral medication.
• With a life expectancy of at least 3 months.
• Female patients of childbearing potential must have a negative urine or serum pregnancy test.
• 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.
• Ability to understand and the willingness to provide a written informed consent document.
• With known central nervous system (CNS) metastases, a history of CNS metastases or leptomeningeal diseases.
• 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.
• 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.

Sponsors & Collaborators

• Taipei Medical University Shuang Ho Hospital: lead

Study Sites (1)

Taipei Medical University Shuang Ho Hospital

New Taipei City, Taiwan

Location

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

N-(2-amino-5-fluorobenzyl)-4-(N-(pyridine-3-acrylyl)aminomethyl)benzamide; HBI-8000; Celecoxib

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Benzenesulfonamides; Sulfonamides; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sulfones; Sulfur Compounds; Pyrazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director, Cancer Center

Model Details: Cohort1: Chidamide(20mg)+Celecoxib(200mg); Cohort2: Chidamide(30mg)+Celecoxib(200mg)

Study Record Dates

• First Submitted: November 15, 2021
• First Posted: March 16, 2022
• Study Start: September 20, 2022
• Primary Completion: March 26, 2024
• Study Completion: March 26, 2024
• Last Updated: December 20, 2024

Record last verified: 2024-12

Locations

TW (1)