Colorectal cancer
Conditions
Interventions
test group:Sintilimab and fruquintinib in combination with capecitabine or S-1 treatment (patients receive either capecitabine or S-1 based on the clinician’s decision)
Sponsors
Nantong Cancer Hospital
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: 1. Signed written informed consent must be obtained prior to the implementation of any study-related procedures. 2. Age >= 18 years. 3. Histologically or cytologically confirmed unresectable metastatic colorectal cancer (mCRC) (AJCC 8th edition, Stage IV). 4. Disease progression during or after second-line standard therapy, as assessed by RECIST v1.1. 5. At least one radiographically measurable lesion per RECIST v1.1. 6. Ability to take oral medication. 7. Eastern Cooperative Oncology Group (ECOG) performance status of 0–1. 8. Expected survival time >3 months. 9. Adequate organ function, with laboratory parameters meeting the following criteria: a. Absolute neutrophil count (ANC) >= 1.5×10?/L without granulocyte-colony stimulating factor administration within the past 14 days. b. Platelet count>= >= 80×10?/L without blood transfusion within the past 14 days. c. Hemoglobin >8 g/dL without blood transfusion or erythropoiesis-stimulating agents within the past 14 days. d. Total bilirubin ULN but direct bilirubin within normal limits. e. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) = 60 mL/min. g. Adequate coagulation function, defined as international normalized ratio (INR) or prothrombin time (PT) <= 1.5×ULN. h. Normal thyroid function, defined as thyroid-stimulating hormone (TSH) within the normal range. Patients with baseline TSH outside the normal range may still be eligible if total triiodothyronine (T3) (or free T3 [FT3]) and free thyroxine (FT4) are within normal limits. i. Normal cardiac enzyme levels (patients with clinically insignificant isolated laboratory abnormalities, as judged by the investigator, may be eligible). (Optional) 10. For female patients of childbearing potential, a urine or serum pregnancy test must be performed within 3 days prior to the first administration of the study drug (Cycle 1, Day 1), with a negative result required for enrollment. If the urine pregnancy test result is indeterminate, a confirmatory blood pregnancy test is required. Women are considered non-childbearing if they are postmenopausal for at least one year or have undergone surgical sterilization or hysterectomy. 11. All patients (male and female) with reproductive potential must use highly effective contraception (annual failure rate <1%) during the entire treatment period and for 120 days after the last dose of study drug (or 180 days after the last dose of chemotherapy, whichever is longer).
Exclusion criteria
Exclusion criteria: 1. Prior treatment with fruquintinib. 2. Prior treatment with any of the following therapies: PD-L1 inhibitors, PD-1 inhibitors, or agents targeting other stimulatory or co-inhibitory T-cell receptors (e.g., CTLA-4, OX-40, CD137). 3. Symptomatic or high-risk conditions, including obstruction, bleeding, perforation, or pneumonitis (including non-infectious pneumonitis requiring prior corticosteroid therapy and pneumonitis under current treatment). 4. Diagnosis of malignancies other than colorectal cancer within 5 years before the first dose, except for radically treated basal cell carcinoma of the skin, squamous cell carcinoma of the skin, and/or in situ carcinoma that has been completely resected. 5. Current participation in an interventional clinical study or receipt of other investigational drugs or investigational devices within 4 weeks before the first dose. 6. Systemic treatment with traditional Chinese medicine with antitumor indications or immunomodulatory agents (e.g., thymosin, interferons, interleukins) within 2 weeks before the first dose, except for localized pleural effusion control. 7. Active autoimmune disease requiring systemic treatment (e.g., disease-modifying agents, corticosteroids, or immunosuppressants) within 2 years before the first dose. Replacement therapy (e.g., thyroid hormone, insulin, or physiological corticosteroids for adrenal or pituitary insufficiency) is not considered systemic treatment. 8. Systemic corticosteroid therapy (excluding nasal, inhaled, or other local corticosteroids) or any other immunosuppressive therapy within 7 days before the first dose. • Note: Physiological doses of corticosteroids <= 10 mg/day prednisone or equivalent) are permitted. 9. Clinically uncontrolled pleural or peritoneal effusion (patients without the need for drainage or those with stable effusion for 3 days after drainage discontinuation may be enrolled). 10. Known history of allogeneic organ transplantation (except corneal transplantation) or allogeneic hematopoietic stem cell transplantation. 11. Known hypersensitivity to sintilimab, fruquintinib, or any excipients of the study drugs. 12. Conditions affecting oral drug intake, such as inability to swallow, history of gastrointestinal surgery, chronic diarrhea, or bowel obstruction. 13. Failure to recover from toxicities and/or complications of prior interventions (i.e., toxicities must have resolved to <= Grade 1 or baseline level, except for fatigue or alopecia). 14. Known history of human immunodeficiency virus (HIV) infection (i.e., HIV 1/2 antibody-positive). 15. Untreated active hepatitis B, defined as HBsAg positivity with detectable HBV DNA exceeding the upper limit of normal (ULN) at the study site’s laboratory. • Note: Patients with hepatitis B may be enrolled if they meet the following criteria: a. HBV viral load <1000 copies/mL (200 IU/mL) before the first dose, and they must receive antiviral therapy throughout the chemotherapy period to prevent HBV reactivation. b. Patients with anti-HBc(+), HBsAg(-), anti-HBs(-), and undetectable HBV DNA do not require prophylactic antiviral therapy but must be closely monitored for viral reactivation. 16. Active hepatitis C infection, defined as positive HCV antibodies with HCV RNA levels above the detection limit. 17. Receipt of a live vaccine within 30 days before the first dose (Cycle 1, Day 1). • Note: Injectable inactivated seasonal influenza vaccines within 30 days before the first dose are allowed, but
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| ORR; | — |
Secondary
| Measure | Time frame |
|---|---|
| DCR;DoR;PFS;OS;Safety; | — |
Countries
China
Contacts
Public ContactXiaohong Xu
Nantong Cancer Hospital
Outcome results
None listed