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Sintilimab and Chidamide in Combination With or Without IBI305 in Advanced or Metastatic pMMR/MSS Colorectal Carcinoma

Primary Purpose

Advanced Microsatellite Stable Colorectal Cancer, Metastatic Microsatellite-stable Colorectal Cancer

Status

Active

Phase

Phase 2

Locations

China

Study Type

Interventional

Intervention

Sintilimab

Chidamide

IBI305

About this trial

This is an interventional treatment trial for Advanced Microsatellite Stable Colorectal Cancer focused on measuring Colorectal Carcinoma, pMMR, Microsatellite-stable

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Histologically confirmed diagnosis of unresectable locally advanced, recurrent or metastatic colorectal adenocarcinoma.
Tumor tissues were identified as mismatch repair-proficient (pMMR) by immunohistochemistry (IHC) method or microsatellite stability (MSS) by polymerase chain reaction (PCR).
Subjects must have failed at least two lines of prior treatment.
Subjects must have one measurable lesion according to RECIST v1.1 at least.
Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
18-75 years old.
Life expectancy of at least 12 weeks.
Adequate bone marrow, liver, renal and coagulation function as assessed by the laboratory required by protocol

Exclusion Criteria:

Previously received anti-programmed death-1 (PD-1) or its ligand (PD-L1) antibody or histone deacetylase (HDAC) inhibitor.
Received last dose of anti-tumor therapy (chemotherapy, targeted therapy, tumor immunotherapy or arterial embolization) within 3 weeks of the first dose of study medication.
Received radiotherapy with 4 weeks of the first dose of study medication.
Underwent major operation within 4 weeks of the first dose of study medication or open wound, ulcer or fracture.
Known symptomatic central nervous system (CNS) metastasis and/or carcinomatous meningitis. Subjects received prior treatment and have stable disease more than 4 weeks from first dose of study medication are permitted to enroll.
Active, known or suspected autoimmune disease or has a history of the disease within the last 2 years.
Interstitial lung disease requiring corticosteroids.
Active or poorly controlled serious infections.
Significant malnutrition.
Symptomatic congestive heart failure (NYHA Class II-IV) or symptomatic or poorly controlled arrhythmia.
Uncontrolled hypertension (systolic blood pressure ≥ 150 mmHg or diastolic blood pressure ≥ 100 mmHg) despite standard treatment.
Within 6 months prior to the enrollment, history of gastrointestinal perforation and/or fistula, gastrointestinal ulcer, bowel obstruction, extensive bowel resection, Crohn's disease, or ulcerative colitis, intra-abdominal abscesses, or long-term chronic diarrhea.
History or evidence of inherited bleeding diathesis or coagulopathy or thrombus
Any life-threatening bleeding within 3 months prior to the enrollment.
High risk of bleeding.

Sites / Locations

Cancer center of Sun Yat-sen University

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

The triplet group (sintilimab + chidamide + IBI305)

The doublet group (sintilimab + chidamide)

Arm Description

Every 3 weeks, patients received sintilimab 200 mg and IBI305(bevacizumab) 7.5 mg/kg on day one and chidamide 30 mg orally twice weekly.

Every 3 weeks, patients received sintilimab 200 mg on day one and chidamide 30 mg orally twice weekly.

Outcomes

Primary Outcome Measures

The progression-free survival (PFS) rates at 18 weeks

The proportion of patients without disease progression or death at the 18th week after initiation of the study treatment

Secondary Outcome Measures

Objective response rate (ORR)

The proportion of patients with a PR or CR

Progression-free survival (PFS);

The time from enrollment until tumor progression or death from any cause, whichever occurred first

Overall Survival (OS);

The time calculated from enrollment until death from any cause, with living patients censored at the last known survival date

Disease control rate (DCR)

The proportion of patients with a PR, CR, or SD

Duration of response (DoR)

For patients who achieved a complete response (CR) or partial response (PR), the time from the first tumor assessment demonstrating response until disease progression or death, whichever occurred first

Full Information

NCT ID

NCT04724239

First Posted

January 25, 2021

Last Updated

July 27, 2023

Sponsor

Sun Yat-sen University

1. Study Identification

Unique Protocol Identification Number

NCT04724239

Brief Title

Sintilimab and Chidamide in Combination With or Without IBI305 in Advanced or Metastatic pMMR/MSS Colorectal Carcinoma

Official Title

A Randomized Phase 2 Clinical Trial Evaluating Sintilimab and Chidamide in Combination With or Without IBI305 in Patients With Standard Treatment Failure of Advanced or Metastatic pMMR/MSS Colorectal Carcinoma

Study Type

Interventional

2. Study Status

Record Verification Date

July 2023

Overall Recruitment Status

Active, not recruiting

Study Start Date

March 11, 2021 (Actual)

Primary Completion Date

July 26, 2022 (Actual)

Study Completion Date

December 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Sun Yat-sen University

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief Summary

The purpose of this study is to evaluate the efficacy and safety of sintilimab and chidamide in combination with or without IBI305(bevacizumab) in patients with standard treatment failure of advanced or metastatic pMMR/MSS colorectal adenocarcinoma.

Detailed Description

In this study, we explored the potential effectiveness of combining PD-1 monoclonal antibody sintilimab with the histone deacetylase inhibitor (HDACi) chidamide, with or without IBI305(bevacizumab), in MSS/pMMR unresectable locally advanced or metastatic colorectal cancer patients who failed standard chemotherapy and testified this new combination in preclinical models. Fourty-eight patients were randomized into two groups: the doublet group, who received sintilimab 200 mg every 3 weeks and chidamide 30 mg orally twice weekly, and the triplet group, who received sintilimab, chidamide, and bevacizumab 7.5 mg/kg every 3 weeks.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Advanced Microsatellite Stable Colorectal Cancer, Metastatic Microsatellite-stable Colorectal Cancer

Keywords

Colorectal Carcinoma, pMMR, Microsatellite-stable

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Model Description

Subjects will be randomized in approximately a 1:1 ratio to receive sintilimab and chidamide with or without IBI305.

Masking

None (Open Label)

Allocation

Randomized

Enrollment

48 (Actual)

8. Arms, Groups, and Interventions

Arm Title

The triplet group (sintilimab + chidamide + IBI305)

Arm Type

Experimental

Arm Description

Every 3 weeks, patients received sintilimab 200 mg and IBI305(bevacizumab) 7.5 mg/kg on day one and chidamide 30 mg orally twice weekly.

Arm Title

The doublet group (sintilimab + chidamide)

Arm Type

Active Comparator

Arm Description

Every 3 weeks, patients received sintilimab 200 mg on day one and chidamide 30 mg orally twice weekly.

Intervention Type

Drug

Intervention Name(s)

Sintilimab

Intervention Description

200mg IV on Day 1 Q3W

Intervention Type

Drug

Intervention Name(s)

Chidamide

Intervention Description

30mg PO BIW each 3-week cycle

Intervention Type

Drug

Intervention Name(s)

IBI305

Other Intervention Name(s)

Bevacizumab

Intervention Description

7.5mg/kg IV on Day 1 Q3W

Primary Outcome Measure Information:

Title

The progression-free survival (PFS) rates at 18 weeks

Description

The proportion of patients without disease progression or death at the 18th week after initiation of the study treatment

Time Frame

24 months

Secondary Outcome Measure Information:

Title

Objective response rate (ORR)

Description

The proportion of patients with a PR or CR

Time Frame

2 year

Title

Progression-free survival (PFS);

Description

The time from enrollment until tumor progression or death from any cause, whichever occurred first

Time Frame

2 year

Title

Overall Survival (OS);

Description

The time calculated from enrollment until death from any cause, with living patients censored at the last known survival date

Time Frame

2 year

Title

Disease control rate (DCR)

Description

The proportion of patients with a PR, CR, or SD

Time Frame

2 year

Title

Duration of response (DoR)

Description

Time Frame

2 year

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Histologically confirmed diagnosis of unresectable locally advanced, recurrent or metastatic colorectal adenocarcinoma. Tumor tissues were identified as mismatch repair-proficient (pMMR) by immunohistochemistry (IHC) method or microsatellite stability (MSS) by polymerase chain reaction (PCR). Subjects must have failed at least two lines of prior treatment. Subjects must have one measurable lesion according to RECIST v1.1 at least. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1. 18-75 years old. Life expectancy of at least 12 weeks. Adequate bone marrow, liver, renal and coagulation function as assessed by the laboratory required by protocol Exclusion Criteria: Previously received anti-programmed death-1 (PD-1) or its ligand (PD-L1) antibody or histone deacetylase (HDAC) inhibitor. Received last dose of anti-tumor therapy (chemotherapy, targeted therapy, tumor immunotherapy or arterial embolization) within 3 weeks of the first dose of study medication. Received radiotherapy with 4 weeks of the first dose of study medication. Underwent major operation within 4 weeks of the first dose of study medication or open wound, ulcer or fracture. Known symptomatic central nervous system (CNS) metastasis and/or carcinomatous meningitis. Subjects received prior treatment and have stable disease more than 4 weeks from first dose of study medication are permitted to enroll. Active, known or suspected autoimmune disease or has a history of the disease within the last 2 years. Interstitial lung disease requiring corticosteroids. Active or poorly controlled serious infections. Significant malnutrition. Symptomatic congestive heart failure (NYHA Class II-IV) or symptomatic or poorly controlled arrhythmia. Uncontrolled hypertension (systolic blood pressure ≥ 150 mmHg or diastolic blood pressure ≥ 100 mmHg) despite standard treatment. Within 6 months prior to the enrollment, history of gastrointestinal perforation and/or fistula, gastrointestinal ulcer, bowel obstruction, extensive bowel resection, Crohn's disease, or ulcerative colitis, intra-abdominal abscesses, or long-term chronic diarrhea. History or evidence of inherited bleeding diathesis or coagulopathy or thrombus Any life-threatening bleeding within 3 months prior to the enrollment. High risk of bleeding.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Ruihua Xu, MD, PhD

Organizational Affiliation

Sun Yat-sen University

Official's Role

Principal Investigator

Facility Information:

Facility Name

Cancer center of Sun Yat-sen University

City

Guangzhou

State/Province

Guangdong

ZIP/Postal Code

510060

Country

China

12. IPD Sharing Statement

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Sintilimab and Chidamide in Combination With or Without IBI305 in Advanced or Metastatic pMMR/MSS Colorectal Carcinoma

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