Comparing Chidamide+Sintilimab+Bev With Standard Second-line FOLFIRI+Bev in Advanced MSS/pMMR mCRC

NCT05768503 | Recruiting Phase 3

• 1 other identifier: CAPability-02
• Study Type: interventional
• Target: 176
• Locations: 1 country
• Sites: 12

Brief Summary

This is a randomized, controlled, multicenter phase Ⅲ study to evaluate the therapeutic efficacy and safety of chidamide + sintilimab + bevacizumab versus standard second-line FOLFIRI + bevacizumab therapy in subjects with advanced microsatellite stable colorectal cancer who have failed first-line oxaliplatin-containing standard therapy. The primary purpose is to compare the progression-free survival (PFS) of chidamide + sintilimab + bevacizumab versus standard second-line FOLFIRI + bevacizumab therapy for colorectal cancer, with a planned enrollment of 176 subjects with advanced microsatellite stable colorectal cancer who have failed first-line oxaliplatin-containing standard therapy.

Conditions

Metastatic Microsatellite-stable Colorectal Cancer

Keywords

Colorectal Cancer; Microsatellite Stable; Chidamide; Sintilimab; PD-1; Bevacizumab

Outcome Measures

Primary Outcomes (1)

• Progression-Free Survival (PFS)

  Time from randomization to disease progression or death from any cause

  Around 4 years

Secondary Outcomes (6)

• Objective Response Rates (ORR)

  Around 4 years

• Overall Survival (OS)

  Around 4 years

• Disease Control Rate (DCR)

  Around 4 years

• Duration of Response (DOR)

  Around 4 years

• Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30)

  Around 4 years

Study Arms (2)

Chidamide + Sintilimab + Bevacizumab Group

EXPERIMENTAL

The treatment option for the chidamide + sintilimab + bevacizumab is 200 mg of sintilimab IV Drip Q3W, 30 mg of chidamide PO BIW, and bevacizumab 7.5 mg/kg IV Drip Q3W until loss of clinical benefit or development of intolerable toxicity (whichever occurs first), with a maximum treatment duration of 2 years.

Drug: Experimental drug

FOLFIRI + Bevacizumab Group

ACTIVE COMPARATOR

The treatment option for the standard second-line FOLFIRI + bevacizumab therapy group is bevacizumab 5 mg/kg IV Drip Q2W, irinotecan 180 mg/m2 IV Drip Q2W, calcium folinate 400 mg/m2 IV Q2W or calcium levofolinate 200 mg/m2 IV Drip Q2W, 5-fluorouracil 400 mg/m2 IV +2400 mg/m2 CIV (infusion 46-48 hr) Q2W until loss of clinical benefit or development of intolerable toxicity (whichever occurs first), with a maximum treatment duration of 2 years.

Drug: Control Rx

Interventions

Experimental drug DRUG

The treatment option for the chidamide + sintilimab + bevacizumab is 200 mg of sintilimab IV Drip Q3W, 30 mg of chidamide PO BIW, and bevacizumab 7.5 mg/kg IV Drip Q3W until loss of clinical benefit or development of intolerable toxicity (whichever occurs first), with a maximum treatment duration of 2 years.

Also known as: CAP

Chidamide + Sintilimab + Bevacizumab Group

Control Rx DRUG

The treatment option for the standard second-line FOLFIRI + bevacizumab therapy group is bevacizumab 5 mg/kg IV Drip Q2W, irinotecan 180 mg/m2 IV Drip Q2W, calcium folinate 400 mg/m2 IV Q2W or calcium levofolinate 200 mg/m2 IV Drip Q2W, 5-fluorouracil 400 mg/m2 IV +2400 mg/m2 CIV (infusion 46-48 hr) Q2W until loss of clinical benefit or development of intolerable toxicity (whichever occurs first), with a maximum treatment duration of 2 years.

Also known as: FOLFIRI+BEV

FOLFIRI + Bevacizumab Group

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Locally advanced unresectable or metastatic colorectal adenocarcinoma (excluding mixed adenosquamous carcinoma and other pathological types) confirmed by pathological histology or cytology.
• Diagnosis of pMMR confirmed by PCR for microsatellite stability (MSS) or low microsatellite instability (MSI-L), or by immunohistochemistry for DNA mismatch repair (MMR) proteins, including MLH1, MSH2, MSH6 and PMS2 protein expression, which result in no protein deletion.
• Patients who have failed first-line oxaliplatin-containing standard therapy and have imaging evidence (e.g., CT scan) or clinical evidence (e.g., cytology report of new ascites or pleural effusion) of disease progression during or after treatment; patients whose intolerance of toxicity has led to discontinuation of first-line oxaliplatin-containing standard therapy may be enrolled; relapse within 180 days after the last dose of oxaliplatin-containing adjuvant therapy.
• There is at least one measurable lesion according to RECIST v1.1.
• ECOG PS score is in the range of 0\~1.
• Subjects who have signed a written informed consent form and who are able to comply with the visits and related procedures specified in the protocol.
• Aged ≥ 18 years old and ≤ 75 years old.
• Expected survival time ≥ 18 weeks.
• Female subjects of childbearing age or male subjects whose sexual partners are at childbearing age are required to take effective contraception measures throughout the treatment period and for 6 months after the treatment (see section 4.3 of the protocol).
• Subjects having adequate organ and bone marrow functions with laboratory test values within 7 days prior to enrollment meeting the following requirements (no blood components, cell growth factors, albumin, and other corrective therapy drugs are allowed to be given within the first 14 days of obtaining laboratory tests), as follows:
• \) Blood routine: absolute neutrophil count (ANC) ≥ 1.5×109/L; platelet count (PLT) ≥ 100×109/L; hemoglobin level (HGB) ≥ 9.0 g/dL.
• \) Liver function: serum total bilirubin (TBIL) ≤ 1.5 × upper limit of normal (ULN); alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3.0 × ULN in subjects without liver metastases, and ALT and AST ≤ 5.0 × ULN in subjects with liver metastases; serum albumin ≥ 25 g/L.
• \) Renal function: serum creatinine (Cr) ≤ 1.5 x ULN. 4) Patients with routine urine results showing urine protein \<2+ or routine urine testing showing urine protein ≥ 2+ at baseline should undergo 24-hour urine collection and 24-hour urine protein quantification \< 1 g.
• \) Coagulation function: international normalized ratio (INR) ≤ 1.5×ULN and activated partial thromboplastin time (APTT) ≤ 1.5×ULN.

You may not qualify if:

• Prior exposure to any anti-PD-1 antibody, anti-PD-L1 antibody, HDAC inhibitor, or irinotecan.
• Receiving any investigational drug within 4 weeks prior to the first dose of the study drug.
• Concurrent participation in another interventional clinical study, except in an observational (non-interventional) clinical study or in the follow-up phase of an interventional study.
• Receiving the last dose of antitumor therapy (chemotherapy, targeted therapy, tumor immunotherapy, or tumor embolization) within 3 weeks prior to the first dose.
• Receiving radiotherapy within 4 weeks prior to the first dose.
• Patients who have received radiotherapy more than 4 weeks prior to the first dose with any radiotherapy-related toxic reactions, such as radiation pneumonia, radiation hepatitis, radiation enteritis, including clinical symptoms only, or requiring glucocorticoid therapy.
• Use of immunosuppressive drugs within 4 weeks prior to the first dose, excluding topical glucocorticoids by nasal spray, inhalation or other routes or physiological doses of systemic glucocorticoids (i.e., no more than 10 mg/day prednisone or equivalent doses of other glucocorticoids).
• Receiving live attenuated vaccine within 4 weeks prior to the first dose or planning to receive during the study period.
• Major surgical procedure (craniotomy, thoracotomy or open heart surgery) or unhealed wound, ulcer or fracture within 4 weeks prior to the first dose.
• Presence of toxicity (excluding alopecia, non-clinically significant and asymptomatic laboratory abnormalities) from prior antineoplastic therapy not recovered to ≤ grade 1 by NCI common terminology criteriafor adverse events (CTCAE) Version 5.0 (NCI CTCAE Version 5.0) prior to the first dose.
• Known presence of symptomatic CNS metastases and/or carcinomatous meningitis. Subjects with prior treatment for brain metastases may participate in the study provided that the brain metastases have remained stable for at least 4 weeks prior to the first dose of study treatment; and that neurological symptoms have recovered to ≤ grade 1 by NCI CTCAE version 5.0.
• Active autoimmune disease requiring systemic therapy (e.g., use of disease-relieving drugs, corticosteroids, or immunosuppressants) within 2 years prior to the first dose. Alternative therapies (e.g., thyroxine, insulin, or physiologic corticosteroids for adrenal or pituitary insufficiency) are allowed. A known history of primary immunodeficiency. For patients with only positive autoimmune antibodies, the presence of autoimmune diseases should be confirmed at the discretion of the investigator.
• Patients who are known to have active tuberculosis and are receiving anti-tuberculosis treatment or have received anti-tuberculosis treatment within 1 year prior to the first dose.
• Known to have interstitial lung disease requiring steroid hormone therapy.
• Known to have acute or chronic active hepatitis B (HBsAg positive and HBV DNA ≥ 200 IU/mL or ≥ 103 copies/mL) or acute or chronic active hepatitis C (HCV antibody positive and HCV RNA positive).

Sponsors & Collaborators

• Sun Yat-sen University: lead

Study Sites (12)

Anhui Provincial Cancer Hospital

Hefei, Anhui, China

NOT YET RECRUITING

The First People's Hospital of Foshan

Foshan, Guangdong, China

NOT YET RECRUITING

Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, 510060, China

RECRUITING

The Third Affiliated Hospital of Sun Yat-sen University

Guangzhou, Guangdong, China

NOT YET RECRUITING

The First Affiliated Hospital of Guangxi Medical University

Nanning, Guangxi, China

NOT YET RECRUITING

Harbin Medical University Cancer Hospital

Harbin, Heilongjiang, China

NOT YET RECRUITING

Henan Cancer Hospital

Zhengzhou, Henan, China

NOT YET RECRUITING

The First Affiliated Hospital of Nanchang University

Nanchang, Jiangxi, China

NOT YET RECRUITING

Ruijin Hospital, Shanghai Jiaotong University School of Medicine

Shanghai, Shanghai Municipality, China

NOT YET RECRUITING

West China Hospital of Sichuan University

Chengdu, Sichuan, China

NOT YET RECRUITING

The Second Affiliated Hospital of Kunming Medical University

Kunming, Yunnan, China

NOT YET RECRUITING

The First Affiliated Hospital of Zhejiang University College of Medicine

Hangzhou, Zhejiang, China

NOT YET RECRUITING

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Drugs, Investigational; Tin Fluorides

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)

Pharmaceutical Preparations; Fluorides; Hydrofluoric Acid; Fluorine Compounds; Inorganic Chemicals; Tin Compounds; Cariostatic Agents; Biomedical and Dental Materials; Manufactured Materials; Technology, Industry, and Agriculture

Study Officials

• Ruihua Xu, MD

  Sun Yat-sen University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ruihua Xu, MD

CONTACT

+86 20 87343795; xurh@sysucc.org.cn

Feng Wang, MD,PhD

CONTACT

+86 20 87343795; wangfeng@sysucc.org.cn

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, President

Model Details: 176 subjects will be randomized in a 1:1 ratio into either the chidamide + sintilimab + bevacizumab group or the standard second-line FOLFIRI + bevacizumab therapy group.

Study Record Dates

• First Submitted: February 16, 2023
• First Posted: March 14, 2023
• Study Start: March 1, 2023
• Primary Completion: January 1, 2026
• Study Completion (Estimated): January 1, 2027
• Last Updated: March 14, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will not share

Locations

CN (12)