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Metastatic Microsatellite-stable Colorectal CancerPhase 3NCT05768503

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

A Phase 3 study testing Experimental drug in people with Metastatic Microsatellite-stable Colorectal Cancer, run by Sun Yat-sen University at 12 sites in China.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial 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… Read more about this study

Who is it for?
Ages 18 to 75 years
What is being tested?
Experimental drug
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
176 participants
Where
12 sitesChina
Study dates
1 Mar 2023to Jan 2027
Phase
Phase 3
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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:
  • 1) Blood routine: absolute neutrophil count (ANC) ≥ 1.5×109/L; platelet count (PLT) ≥ 100×109/L; hemoglobin level (HGB) ≥ 9.0 g/dL.
  • 2) 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.
  • 3) 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.
  • 5) Coagulation function: international normalized ratio (INR) ≤ 1.5×ULN and activated partial thromboplastin time (APTT) ≤ 1.5×ULN.

Who cannot join

  • 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.
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  • 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).
  • Infected with human immunodeficiency virus (HIV) (HIV 1/2 antibody positive), known to be infected with syphilis.
  • Severe infections that are in the active phase or poorly controlled in clinical practice. Serious infection, including but not limited to hospitalization for complications of infection, bacteremia or severe pneumonia, within 4 weeks prior to the first dose.
  • Significant malnutrition, such as the need for intravenous supplemental nutrient solutions; except for malnutrition corrected more than 4 weeks prior to the first dose.
  • Symptomatic congestive heart failure (New York Heart Association class II-IV); symptomatic or poorly controlled arrhythmias.
  • Uncontrolled arterial hypertension (systolic blood pressure ≥ 150 mmHg or diastolic blood pressure ≥ 100 mmHg) even with standard treatment.
  • Any arterial thromboembolic event including myocardial infarction, pulmonary embolism, and unstable angina within 6 months prior to enrollment.
  • A history of deep vein thrombosis or any other serious thromboembolism (implantable IV port or catheter-derived thrombosis, or superficial vein thrombosis is not considered "serious" thromboembolism) within 3 months prior to enrollment.
  • Hepatic encephalopathy, hepatorenal syndrome, or Child-Pugh class B or more severe cirrhosis.
  • A history of gastrointestinal perforation and/or fistula in the previous 6 months; a history of peptic ulcer, a history of intestinal obstruction (including incomplete intestinal obstruction requiring parenteral nutrition), extensive bowel resection (partial colectomy or extensive small bowel resection complicated by chronic diarrhea), Crohn's disease, ulcerative colitis, abdominal abscess, or long-term chronic diarrhea. Post-intestinal stent implantation.
  • > 3 loose stools per day at baseline, suggesting a predisposition to colon or small bowel disease with uncontrollable symptoms.
  • A history of allergy or known intolerance to atropine sulfate or loperamide or the appropriate antiemetic in combination with FOLFIRI.
  • Uncontrolled metabolic disorders or other non-malignant organ or systemic diseases or secondary reactions to cancer and can lead to higher medical risk and/or uncertainty in survival evaluation.
  • A known history of inherited bleeding tendency disorders or coagulation disorders
  • Any life-threatening bleeding event within the previous 3 months, including the need for blood transfusion therapy, surgical or local treatment, or ongoing drug therapy.
  • A high risk of bleeding as determined by the investigators: cirrhosis with severe esophagogastric fundic varices, intermittent or persistent non-fatal bleeding events (including but not limited to intermittent bloody stools or positive occult blood due to primary intestinal lesions, intermittent hemoptysis due to pulmonary metastases).
  • Cerebrovascular accident (including transient ischemic attack) in the previous 6 months.
  • Use of aspirin (>325 mg/day) or other NSAIDs known to inhibit platelet function for 10 consecutive days within 10 days prior to the first dose.
  • Treatment with oral or parenteral anticoagulants or thrombolytics for 10 consecutive days within 10 days prior to the first dose. However, prophylactic use of anticoagulants is allowed.
  • Pleural fluid, ascites, and pericardial effusion with clinical symptoms or requiring drainage, except for small amounts of pleural fluid, small amounts of ascites, and small amounts of pericardial effusion without clinical symptoms on imaging only.
  • A history of other primary malignancies, except: malignancies in complete response for at least 2 years prior to enrollment and requiring no other treatment during the study period; adequately treated non-melanoma skin cancer or malignant freckled nevus with no evidence of disease recurrence; adequately treated carcinoma in situ with no evidence of disease recurrence.
  • A known history of allogeneic organ transplantation and allogeneic hematopoietic stem cell transplantation.
  • Known to be allergic to any monoclonal antibody component.
  • Female subjects in the pregnancy or lactating period.
  • A history of alcohol or drug abuse.
  • Other acute or chronic illnesses, psychiatric disorders, or abnormal laboratory test values that may result in the following outcomes: increasing the risk associated with study participation or study drug administration, or interfering with the interpretation of study results and, at the investigator's discretion, classifying the patient as ineligible for participation in this study.

Trial locations and contacts

12 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Ruihua Xu, MD contact

+86 20 87343795

xurh@sysucc.org.cn

Feng Wang, MD,PhD contact

+86 20 87343795

wangfeng@sysucc.org.cn

12 sites in 1 country

China12 sites, 12 recruiting

  • West China Hospital of Sichuan University

    Chengdu, Sichuan

    Meng Qiu

    Guixia Wei

    Not yet recruiting

  • The First People's Hospital of Foshan

    Foshan, Guangdong

    Wei Wang

    Wei Wang

    Not yet recruiting

  • Sun Yat-sen University Cancer Center

    Guangzhou, Guangdong, 510060

    Ruihua Xu, MD, +862087343795, xurh@susycc.org.cn

    Feng Wang, MD,PhD, +862087343795

    Recruiting

  • The Third Affiliated Hospital of Sun Yat-sen University

    Guangzhou, Guangdong

    Xiangyuan Wu

    Min Dong

    Not yet recruiting

  • The First Affiliated Hospital of Zhejiang University College of Medicine

    Hangzhou, Zhejiang

    Weijia Fang

    Lulu Liu

    Not yet recruiting

  • Harbin Medical University Cancer Hospital

    Harbin, Heilongjiang

    Yanqiao Zhang, MD

    Yanqiao Zhang, MD

    Not yet recruiting

  • Anhui Provincial Cancer Hospital

    Hefei, Anhui

    Yifu He

    Lulu Cao

    Not yet recruiting

  • The Second Affiliated Hospital of Kunming Medical University

    Kunming, Yunnan

    Xuefen Lei

    Yixuan Chen

    Not yet recruiting

  • The First Affiliated Hospital of Nanchang University

    Nanchang, Jiangxi

    Xiaojun Xiang

    Yan He

    Not yet recruiting

  • The First Affiliated Hospital of Guangxi Medical University

    Nanning, Guangxi

    Xiaohua Hu

    Zhigang Peng

    Not yet recruiting

  • Ruijin Hospital, Shanghai Jiaotong University School of Medicine

    Shanghai, Shanghai Municipality

    Jun Zhang

    Chengfang Shangguan

    Not yet recruiting

  • Henan Cancer Hospital

    Zhengzhou, Henan

    Xiaobing Chen

    Caiyun Nie

    Not yet recruiting

Other trials in China

About this study

Official title: Chidamide+Sintilimab+Bevacizumab Versus Standard Second-Line Therapy of FOLFIRI+Bevacizumab in Subjects With Advanced Microsatellite Stable (MSS/pMMR) Colorectal Cancer Who Have Failed Oxaliplatin-Containing First-Line Therapy

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.

Read the detailed description

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. The treatment option for the chidamide + sintilimab + bevacizumab (study group) is 200 mg of sintilimab IV Drip Q3W, 30 mg of chidamide PO BIW, and bevacizumab 7.5 mg/kg IV Drip Q3W, with a maximum treatment duration of 2 years. The treatment option for the standard second-line FOLFIRI + bevacizumab therapy group (control 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 Q2W, with a maximum treatment duration of 2 years.

The primary endpoint of this study is the progression-free survival (PFS), defined as the time from random assignment of the subject to disease progression or death from any cause.

All eligible patients will be randomly assigned to either the trial or control group in a 1:1 ratio based on the following stratification factors: Whether the primary focus is located in the right-sided colorectum; Whether bevacizumab has been administered in the first-line treatment.

Being tested
Experimental drug, Control Rx
Keywords
Colorectal Cancer, Microsatellite Stable, Chidamide, Sintilimab, PD-1, Bevacizumab
Medical subject headings
Colorectal Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Experimental drugDrug

    Also called CAP

    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.

  • Control RxDrug

    Also called FOLFIRI+BEV

    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.

Study groups in NCT05768503
Study groupRoleWhat they receive
Chidamide + Sintilimab + Bevacizumab GroupExperimentalThe 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.
Receives: Drug: Experimental drug
FOLFIRI + Bevacizumab GroupActive comparatorThe 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.
Receives: Drug: Control Rx

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Progression-Free Survival (PFS)

    Time from randomization to disease progression or death from any cause

    Measured: Around 4 years

Secondary outcomes (6)

  1. Objective Response Rates (ORR)

    The percentage of subjects whose therapeutic effect evaluation is complete response (CR) or partial response (PR) according to RECIST 1.1.

    Measured: Around 4 years

  2. Overall Survival (OS)

    Time from randomization to death from any cause

    Measured: Around 4 years

  3. Disease Control Rate (DCR)

    The percentage of subjects whose therapeutic effect evaluation is complete response (CR), partial response (PR) or stable disease (SD) according to RECIST 1.1.

    Measured: Around 4 years

  4. Duration of Response (DOR)

    Time from achievement of a response to disease progression.

    Measured: Around 4 years

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

    Quality of life is assessed using the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ) C30. It will be evaluated at Screening, Tumor Assessment Visit (Week 8 and 12) and End of Treatment visit. The higher score means the worse quality of life.

    Measured: Around 4 years

  6. Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-CR29 (EORTC QLQ-CR29)

    Quality of life in patients with colorectal cancer is assessed using the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ) CR29. It will be evaluated at Screening, Tumor Assessment Visit (Week 8 and 12) and End of Treatment visit. The higher score means the worse quality of life.

    Measured: Around 4 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted14 Mar 2023
  2. Study start1 Mar 2023
  3. Primary completionJan 2026 (estimated)
  4. Study completionJan 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
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.
Masking
None (open label)
Enrolment
176 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05768503
Sponsor's protocol ID
CAPability-02
Status last verified
Mar 2023
First submitted
16 Feb 2023
Last updated
14 Mar 2023
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Experimental drug in people with Metastatic Microsatellite-stable Colorectal Cancer, run by Sun Yat-sen University at 12 sites in China.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 14 inclusion and 40 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 14 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 12 sites in China. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Ruihua Xu, MD (+86 20 87343795, xurh@sysucc.org.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression-Free Survival (PFS) (time frame: Around 4 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05768503.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Mar 2023.

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