Immunotherapy, Metastatic Colorectal Cancer With Left-sided Primary Tumor
Conditions
Brief summary
This is a two-arm, randomized phase II clinical study. It is planned to enroll 44 patients with primary left-sided, RAS and BRAF wild-type metastatic colorectal cancer. After signing the informed consent, eligible subjects will be screened to enter the clinical study and assigned to two treatment groups using simple randomization and allocation concealment methods. The treatment plans for the two groups are as follows: Group A: FOLFOXIRI (Irinotecan 165mg/m², iv, d1; Oxaliplatin 85mg/m², iv, d1; (Levo) Folinic Acid (200) 400mg/m², iv, d1; total 5-FU 2400mg/m², iv gtt (continuous for 48h), d1) + Bevacizumab (5mg/kg, i.v, Q2W) Group B: FOLFOX (Oxaliplatin 85mg/m², iv gtt (for 2h), d1; (Levo) Folinic Acid (200) 400mg/m², iv gtt (for 2h), d1; 5-FU 400mg/m², iv, followed by 2400mg/m², iv gtt (continuous for 46-48h), d1) + Cetuximab (500mg/m², i.v, Q2W) Both groups A and B will repeat the treatment every 2 weeks, for a maximum of 9 cycles. Then, the attending physician will decide whether to conduct maintenance treatment (Capecitabine or 5FU/LV with or without Bevacizumab is recommended). Both groups A and B will be combined with QL1706 (5mg/kg, i.v, Q3W) for a maximum of 52 weeks. Medication will continue until the researcher judges that there is no longer clinical benefit (the researcher makes a comprehensive judgment based on RECIST v1.1 imaging evaluation and clinical status, etc.), intolerable toxicity occurs, the subject withdraws informed consent, or other criteria for terminating treatment in the protocol are met, whichever comes first.
Interventions
DRUGFOLFOXIRI + QL1706 + Bevacizumab
FOLFOXIRI(Irinotecan 165mg/m², iv, d1; Oxaliplatin 85mg/m², iv, d1; (Levo) Folinic Acid (200) 400mg/m², iv, d1; total 5-FU 2400mg/m², iv gtt (continuous for 48h), d1) + QL1706 (5mg/kg, i.v., Q3W) + Bevacizumab (5mg/kg, i.v., Q2W)
DRUGFOLFOX+QL1706+Cetuximab
FOLFOX (Oxaliplatin 85mg/m², iv gtt (for 2h), d1; (Levo) Folinic Acid (200) 400mg/m², iv gtt (for 2h), d1; 5-FU 400mg/m², iv, followed by 2400mg/m², iv gtt (continuous for 46-48h), d1) + QL1706 (5mg/kg, i.v., Q3W) + Cetuximab (500mg/m², i.v., Q2W).
Sponsors
Fujian Cancer Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Age 18 to 75 years old. 2. Eastern Cooperative Oncology Group (ECOG) performance status score of 0-1. 3. Histologically or cytologically confirmed metastatic colorectal adenocarcinoma with the primary tumor located in the left-sided colon (from the splenic flexure to the rectum), including cecal adenocarcinoma. 4. Presence of at least one evaluable lesion according to RECIST v1.1 criteria. 5. The subject has provided sufficient tumor tissue samples through colonoscopy biopsy for MSI, TMB, and other tests. 6. Tumors confirmed by tissue testing to be wild-type for KRAS, NRAS, and BRAF. 7. Within 7 days prior to the first dose of study drug, laboratory tests meet the following criteria (no blood products, hematopoietic growth factors, albumin, or other corrective treatments within 14 days prior to testing): (1) Biochemistry: Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 times the upper limit of normal (ULN), or ≤ 5 times ULN in the presence of liver metastases; total bilirubin (TBIL) ≤ 1.5 times ULN, or ≤ 2 times ULN in the presence of liver metastases; serum creatinine ≤ 1.5 times ULN, or creatinine clearance \> 50 mL/min (calculated by the Cockcroft-Gault formula). (2) Hematology: Hemoglobin (Hb) ≥ 9.0 g/dL. No red blood cell transfusions within 1 week prior to the baseline Hb test; absolute neutrophil count (ANC) ≥ 1.5 × 10⁹/L; platelet count ≥ 100 × 10⁹/L. No platelet transfusions within 1 week prior to the baseline platelet test. (3) Coagulation function: International normalized ratio (INR) ≤ 1.5 × ULN (for subjects receiving prophylactic anticoagulation therapy without active bleeding \[i.e., no bleeding within the past 14 days\], the investigator should determine that the INR is within a safe and effective therapeutic range). (4) Urinalysis: Urine protein ≤ 30 mg/dL (1+) by dipstick or routine urinalysis (if ≥ 2+, then a 24-hour urine protein quantification must be \< 1 g/24h). 8. Estimated survival of at least 3 months. 9. No contraindications to chemotherapy or immunotherapy. 10. Women of childbearing potential must have a negative serum pregnancy test within 7 days prior to enrollment and agree to use a reliable and effective method of contraception during the study and for 5 months after the last dose of study drug. Men whose partners are women of childbearing potential must agree to use a reliable and effective method of contraception during the study and for 5 months after the last dose of study drug. Lactating women are not eligible. 11. The subject must provide informed consent for the study prior to enrollment, voluntarily sign a written informed consent form, and be willing and able to comply with the study visit schedule, treatment plan, laboratory tests, and other study procedures.
Exclusion criteria
1. Confirmed by histopathological or cytological examination as other pathological types, such as squamous cell carcinoma, undifferentiated carcinoma, neuroendocrine carcinoma, etc. For mixed pathological types, the determination will be made based on the predominant component; adenocarcinoma component \> 70% confirmed by pathologist is eligible for enrollment. Primary appendiceal tumors are
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate | 18 weeks | The percentage of participants in the analysis dataset who achieve a best overall response of Complete Response (CR) or Partial Response (PR) from the start of treatment until disease progression or withdrawal from the study. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Response | 52 weeks | The time from the first assessment of Complete Response (CR) or Partial Response (PR) until the first assessment of Progressive Disease (PD) or death from any cause. |
| Disease Control Rate | 18 weeks | The proportion of patients whose tumors have shrunk or remained stable for a certain period of time, including cases of Complete Response (CR), Partial Response (PR), and Stable Disease (SD). |
| Progression Free Survival | 52 weeks | The time from the day of enrollment until the first occurrence of disease progression (PD) or death due to any cause. |
| Overall Survival | 52 weeks | It refers to the time from the date of enrollment to the date of death due to any cause. |
| Incidence of Adverse Events | 30 days after the end of study | fatigue, nausea/vomiting, abdominal pain and diarrhea, stomatitis, hepatic dysfunction, myelosuppression, etc. |
Countries
China
Contacts
Primary Contactrongbo lin
Outcome results
None listed