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Trial Title:
Toripalimab Combined With Targeted Therapy and Chemotherapy With or Without Radiotherapy as First-Line Treatment for Advanced Colorectal Cancer
NCT ID:
NCT06521866
Condition:
Advanced Colorectal Carcinoma
Immunotherapy
Conditions: Official terms:
Colorectal Neoplasms
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Not yet recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Toripalimab
Description:
240 mg IV on Day 1, every 3 weeks
Arm group label:
Group A
Arm group label:
Group B
Arm group label:
Group C
Arm group label:
Group D
Intervention type:
Drug
Intervention name:
Chemotherapy
Description:
Induction therapy：Oxaliplatin: 85 mg/m² IV on Day 1 Leucovorin (LV): 400 mg/m² IV on Day
1 5-FU: 400 mg/m² IV bolus on Day 1, then 2400 mg/m² continuous IV infusion over 46-48
hours
Maintenance therapy:
Leucovorin (LV): 400 mg/m² IV on Day 1 5-FU: 400 mg/m² IV bolus on Day 1, then 2400 mg/m²
continuous IV infusion over 46-48 hours
Arm group label:
Group A
Arm group label:
Group B
Arm group label:
Group C
Arm group label:
Group D
Intervention type:
Radiation
Intervention name:
SABR
Description:
SABR: 25-60 Gy/5 Fx
Arm group label:
Group B
Arm group label:
Group D
Intervention type:
Drug
Intervention name:
Targeted therapy
Description:
Cetuximab: 400 mg/m² IV on Day 1, then 250 mg/m² IV weekly Bevacizumab: 5 mg/kg IV on Day
1
Arm group label:
Group A
Arm group label:
Group B
Arm group label:
Group C
Arm group label:
Group D
Summary:
Title: A Prospective, Randomized, Phase II Clinical Study of Toripalimab with Targeted
Therapy and Chemotherapy with or without Radiotherapy for Advanced Colorectal Cancer.
Objective: To assess the efficacy and safety of combining an immune checkpoint inhibitor
with targeted therapy and chemoradiotherapy in patients with locally advanced
unresectable or metastatic colorectal cancer. Design: This study involves left-sided
wild-type and right-sided or RAS-mutant patients who will receive different combinations
of Toripalimab, targeted therapy, chemotherapy, and radiotherapy, with specific treatment
regimens for each cohort. The primary endpoints include PFS, ORR, OS, and safety.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Age ≥ 18 years, any gender;
2. Histologically confirmed metastatic colorectal cancer (Stage IV, UICC), with
initially unresectable metastases or refusal of surgery;
- Primary tumor located in the distal transverse colon, descending colon, sigmoid
colon, and rectum, and RAS (KRAS and NRAS) and BRAF wild-type (Cohorts A and
B);
- Primary tumor located in the cecum, ascending colon, and proximal transverse
colon, and RAS (KRAS and NRAS) mutant-type (Cohorts C and D);
3. Treatment-naive patients who have not received standard anti-tumor therapy;
4. At least one measurable tumor lesion per RECIST 1.1 criteria;
5. ECOG performance status of 0-1;
6. Patients with an expected survival time of ≥ 3 months and good organ function:
- (1) Neutrophils ≥ 1.5 * 10^9/L; platelets ≥ 100 * 10^9/L; hemoglobin ≥ 9 g/dL;
serum albumin ≥ 3 g/dL;
- (2) Thyroid-stimulating hormone (TSH) ≤ upper limit of normal (ULN), T3 and T4
within normal ranges;
- (3) Bilirubin ≤ 1.5 times ULN; ALT and AST ≤ 2 times ULN;
- (4) Serum creatinine ≤ 1.5 times ULN, creatinine clearance rate ≥ 60 mL/min;
- (5) International normalized ratio (INR) or prothrombin time (PT) ≤ 1.5 times
ULN, unless the patient is receiving anticoagulant therapy and PT is within the
expected therapeutic range of anticoagulants;
- (6) Activated partial thromboplastin time (aPTT) ≤ 1.5 times ULN;
7. Female patients of childbearing potential must have a negative pregnancy test;
female patients not of childbearing potential; male patients of reproductive
potential and female patients of reproductive potential and at risk of pregnancy
must agree to use adequate contraception throughout the study period, continuing
until 12 months after the last dose of study treatment;
8. Signed and dated informed consent form indicating that the patient has been informed
of all pertinent aspects of the study;
9. Patients willing and able to comply with visit schedule, treatment plan, laboratory
tests, and other study procedures.
Exclusion Criteria:
1. Pathologically diagnosed with other intestinal tumors, such as gastrointestinal
stromal tumors;
2. No testing for RAS mutation status;
3. Resectable metastases or patients wishing to undergo metastasectomy;
4. Prior systemic therapy. Systemic therapy includes all of the following: chemotherapy
agents such as fluoropyrimidines, irinotecan, and oxaliplatin, VEGF monoclonal
antibodies (e.g., bevacizumab), EGFR monoclonal antibodies (cetuximab or
panitumumab), small molecule TKIs, immune checkpoint inhibitors, etc.;
5. Uncontrolled active bleeding from the primary tumor or bowel obstruction;
6. Contraindications to immune checkpoint inhibitors;
7. Allergy to the therapeutic drugs and/or their excipients;
8. Previous treatment with PD-1 antibodies, PD-L1 antibodies, or CTLA-4 antibodies;
9. Received any form of radiation therapy within 4 weeks prior to enrollment;
10. Previous or concurrent other malignancies, except adequately treated non-melanoma
skin cancer, in situ cervical cancer, or papillary thyroid carcinoma;
11. Active autoimmune disease or history of autoimmune disease (e.g., interstitial
pneumonia, colitis, hepatitis, hypophysitis, vasculitis, nephritis, hyperthyroidism,
hypothyroidism, including but not limited to these diseases or syndromes); except
autoimmune-mediated hypothyroidism on stable doses of thyroid replacement hormone,
type I diabetes on stable doses of insulin, vitiligo, or childhood asthma/allergies
that have resolved and do not require intervention in adulthood;
12. History of immunodeficiency, including HIV-positive, or other acquired/congenital
immunodeficiency diseases, or history of organ transplantation and allogeneic bone
marrow transplantation;
13. History of interstitial lung disease (excluding radiation pneumonitis not treated
with steroids), non-infectious pneumonia;
14. Active tuberculosis infection identified by history or CT scan, or history of active
tuberculosis infection within 1 year prior to enrollment, or history of active
tuberculosis infection more than 1 year ago but without proper treatment;
15. Active hepatitis B (HBV DNA ≥ 2000 IU/mL or 10^4 copies/mL), active hepatitis C (HCV
antibody positive and HCV-RNA above the detection limit);
16. Severe dysfunction of the heart, lungs, or kidneys;
17. Hypertension not well controlled by antihypertensive medications (systolic blood
pressure ≥ 140 mmHg or diastolic blood pressure ≥ 90 mmHg);
18. History of substance abuse, alcoholism, or drug addiction;
19. Any other factors judged by the investigator to potentially affect the safety or
compliance of the patient with the study, such as serious concomitant disease
(including mental illness), serious laboratory abnormalities, or other familial or
social factors.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Start date:
August 1, 2024
Completion date:
August 1, 2027
Lead sponsor:
Agency:
Fudan University
Agency class:
Other
Source:
Fudan University
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06521866
