Trial Title:
Comparing Chidamide+Sintilimab+Bev With Standard Second-line FOLFIRI+Bev in Advanced MSS/pMMR mCRC
NCT ID:
NCT05768503
Condition:
Metastatic Microsatellite-stable Colorectal Cancer
Conditions: Official terms:
Colorectal Neoplasms
Conditions: Keywords:
Colorectal Cancer
Microsatellite Stable
Chidamide
Sintilimab
PD-1
Bevacizumab
Study type:
Interventional
Study phase:
Phase 3
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Intervention 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.
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Experimental drug
Description:
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.
Arm group label:
Chidamide + Sintilimab + Bevacizumab Group
Other name:
CAP
Intervention type:
Drug
Intervention name:
Control Rx
Description:
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.
Arm group label:
FOLFIRI + Bevacizumab Group
Other name:
FOLFIRI+BEV
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.
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.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Locally advanced unresectable or metastatic colorectal adenocarcinoma (excluding
mixed adenosquamous carcinoma and other pathological types) confirmed by
pathological histology or cytology.
2. 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.
3. 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.
4. There is at least one measurable lesion according to RECIST v1.1.
5. ECOG PS score is in the range of 0~1.
6. 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.
7. Aged ≥ 18 years old and ≤ 75 years old.
8. Expected survival time ≥ 18 weeks.
9. 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).
10. 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.
Exclusion Criteria:
1. Prior exposure to any anti-PD-1 antibody, anti-PD-L1 antibody, HDAC inhibitor, or
irinotecan.
2. Receiving any investigational drug within 4 weeks prior to the first dose of the
study drug.
3. 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.
4. Receiving the last dose of antitumor therapy (chemotherapy, targeted therapy, tumor
immunotherapy, or tumor embolization) within 3 weeks prior to the first dose.
5. Receiving radiotherapy within 4 weeks prior to the first dose.
6. 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.
7. 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).
8. Receiving live attenuated vaccine within 4 weeks prior to the first dose or planning
to receive during the study period.
9. Major surgical procedure (craniotomy, thoracotomy or open heart surgery) or unhealed
wound, ulcer or fracture within 4 weeks prior to the first dose.
10. 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.
11. 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.
12. 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.
13. 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.
14. Known to have interstitial lung disease requiring steroid hormone therapy.
15. 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).
16. Infected with human immunodeficiency virus (HIV) (HIV 1/2 antibody positive), known
to be infected with syphilis.
17. 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.
18. Significant malnutrition, such as the need for intravenous supplemental nutrient
solutions; except for malnutrition corrected more than 4 weeks prior to the first
dose.
19. Symptomatic congestive heart failure (New York Heart Association class II-IV);
symptomatic or poorly controlled arrhythmias.
20. Uncontrolled arterial hypertension (systolic blood pressure ≥ 150 mmHg or diastolic
blood pressure ≥ 100 mmHg) even with standard treatment.
21. Any arterial thromboembolic event including myocardial infarction, pulmonary
embolism, and unstable angina within 6 months prior to enrollment.
22. 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.
23. Hepatic encephalopathy, hepatorenal syndrome, or Child-Pugh class B or more severe
cirrhosis.
24. 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.
25. > 3 loose stools per day at baseline, suggesting a predisposition to colon or small
bowel disease with uncontrollable symptoms.
26. A history of allergy or known intolerance to atropine sulfate or loperamide or the
appropriate antiemetic in combination with FOLFIRI.
27. 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.
28. A known history of inherited bleeding tendency disorders or coagulation disorders
29. 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.
30. 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).
31. Cerebrovascular accident (including transient ischemic attack) in the previous 6
months.
32. 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.
33. 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.
34. 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.
35. 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.
36. A known history of allogeneic organ transplantation and allogeneic hematopoietic
stem cell transplantation.
37. Known to be allergic to any monoclonal antibody component.
38. Female subjects in the pregnancy or lactating period.
39. A history of alcohol or drug abuse.
40. 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.
Gender:
All
Minimum age:
18 Years
Maximum age:
75 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Anhui Provincial Cancer Hospital
Address:
City:
Hefei
Country:
China
Status:
Not yet recruiting
Contact:
Last name:
Yifu He
Contact backup:
Last name:
Lulu Cao
Investigator:
Last name:
Yifu He
Email:
Principal Investigator
Investigator:
Last name:
Lulu Cao
Email:
Sub-Investigator
Facility:
Name:
The First People's Hospital of Foshan
Address:
City:
Foshan
Country:
China
Status:
Not yet recruiting
Contact:
Last name:
Wei Wang
Investigator:
Last name:
Wei Wang
Email:
Principal Investigator
Investigator:
Last name:
Fen Feng
Email:
Sub-Investigator
Facility:
Name:
Sun Yat-sen University Cancer Center
Address:
City:
Guangzhou
Zip:
510060
Country:
China
Status:
Recruiting
Contact:
Last name:
Ruihua Xu, MD
Phone:
+862087343795
Email:
xurh@susycc.org.cn
Contact backup:
Last name:
Feng Wang, MD,PhD
Phone:
+862087343795
Investigator:
Last name:
Ruihua Xu, MD
Email:
Principal Investigator
Investigator:
Last name:
Feng Wang, MD, PhD
Email:
Sub-Investigator
Facility:
Name:
The Third Affiliated Hospital of Sun Yat-sen University
Address:
City:
Guangzhou
Country:
China
Status:
Not yet recruiting
Contact:
Last name:
Xiangyuan Wu
Contact backup:
Last name:
Min Dong
Investigator:
Last name:
Xiangyuan Wu
Email:
Principal Investigator
Investigator:
Last name:
Min Dong
Email:
Sub-Investigator
Facility:
Name:
The First Affiliated Hospital of Guangxi Medical University
Address:
City:
Nanning
Country:
China
Status:
Not yet recruiting
Contact:
Last name:
Xiaohua Hu
Contact backup:
Last name:
Zhigang Peng
Investigator:
Last name:
Xioahua Hu
Email:
Principal Investigator
Investigator:
Last name:
Yehong Bin
Email:
Sub-Investigator
Facility:
Name:
Harbin Medical University Cancer Hospital
Address:
City:
Harbin
Country:
China
Status:
Not yet recruiting
Contact:
Last name:
Yanqiao Zhang, MD
Investigator:
Last name:
Yanqiao Zhang, MD
Email:
Principal Investigator
Investigator:
Last name:
Dan Su, MD
Email:
Sub-Investigator
Facility:
Name:
Henan Cancer Hospital
Address:
City:
Zhengzhou
Country:
China
Status:
Not yet recruiting
Contact:
Last name:
Xiaobing Chen
Contact backup:
Last name:
Caiyun Nie
Investigator:
Last name:
Xiaobing Chen
Email:
Principal Investigator
Investigator:
Last name:
Caiyun Nie
Email:
Sub-Investigator
Facility:
Name:
The First Affiliated Hospital of Nanchang University
Address:
City:
Nanchang
Country:
China
Status:
Not yet recruiting
Contact:
Last name:
Xiaojun Xiang
Contact backup:
Last name:
Yan He
Investigator:
Last name:
Xiaojun Xiang
Email:
Principal Investigator
Investigator:
Last name:
Yan He
Email:
Sub-Investigator
Facility:
Name:
Ruijin Hospital, Shanghai Jiaotong University School of Medicine
Address:
City:
Shanghai
Country:
China
Status:
Not yet recruiting
Contact:
Last name:
Jun Zhang
Contact backup:
Last name:
Chengfang Shangguan
Investigator:
Last name:
Jun Zhang
Email:
Principal Investigator
Investigator:
Last name:
Chengfang Shangguan
Email:
Sub-Investigator
Facility:
Name:
West China Hospital of Sichuan University
Address:
City:
Chendu
Country:
China
Status:
Not yet recruiting
Contact:
Last name:
Meng Qiu
Contact backup:
Last name:
Guixia Wei
Investigator:
Last name:
Meng Qiu
Email:
Principal Investigator
Investigator:
Last name:
Guixia Wei
Email:
Sub-Investigator
Facility:
Name:
The Second Affiliated Hospital of Kunming Medical University
Address:
City:
Kunming
Country:
China
Status:
Not yet recruiting
Contact:
Last name:
Xuefen Lei
Contact backup:
Last name:
Yixuan Chen
Investigator:
Last name:
Xuefen Lei
Email:
Principal Investigator
Investigator:
Last name:
Yixuan Chen
Email:
Sub-Investigator
Facility:
Name:
The First Affiliated Hospital of Zhejiang University College of Medicine
Address:
City:
Hangzhou
Country:
China
Status:
Not yet recruiting
Contact:
Last name:
Weijia Fang
Contact backup:
Last name:
Lulu Liu
Investigator:
Last name:
Weijia Fang
Email:
Principal Investigator
Investigator:
Last name:
Zhou Tong
Email:
Sub-Investigator
Start date:
March 1, 2023
Completion date:
January 2027
Lead sponsor:
Agency:
Sun Yat-sen University
Agency class:
Other
Source:
Sun Yat-sen University
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05768503
