Hepatic Arterial Infusion Chemotherapy Combined With Sintilimab and Regorafenib as Adjuvant Therapy for Colorectal Liver Metastasis Patients With a High Risk of Recurrent: a Single-arm, Phase II Study

NCT05753163 | Unknown Phase 2

• 1 other identifier: 2022-GWK-001
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 1

Brief Summary

Pts with histologically confirmed CRLM and whose CRS \>2 were enrolled into this single-arm, phase II study. The critical enrollment criteria were that Subjects had completely resected Primary lesion and liver metastases and had no evidence of extrahepatic disease. After hepatectomy， HAIC (FOLFOX: oxaliplatin 85mg/m2, 5- fluorouracil 2500mg/m2, calcium folinate 400mg/m2) was given every 4-6 weeks for 2-4 cycles depending on pts' health status, in combination with Sintilimab (200mg, iv, d1) and regorafenib (80mg, po, d1-21) every 3 weeks for up to 6 months. The primary endpoint was 1-year recurrence-free survival (RFS) and secondary endpoints included RFS, overall survival (OS), safety, and health-related quality of life.

Conditions

Colorectal Liver Metastasis

Outcome Measures

Primary Outcomes (1)

• 1-year recurrence-free survival rate (1-year RFS)

  Incidence of recurrence-free patients in one year

  12 months

Secondary Outcomes (4)

• recurrence-free survival (RFS)

  Up to approximately 2 years

• overall survival (OS)

  Up to approximately 5 years

• Safety and tolerability

  Up to approximately 2 years

• health-related quality of life (HRQol)

  Up to approximately 2 years

Study Arms (1)

treatment

EXPERIMENTAL

Combination Product: HAIC-FOLFOX combined with Sintilimab and Regorafenib

Interventions

HAIC-FOLFOX combined with Sintilimab and Regorafenib COMBINATION_PRODUCT

HAIC (FOLFOX: oxaliplatin 85mg/m2, 5- fluorouracil 2500mg/m2, calcium folinate 400mg/m2) was given every 4-6 weeks for 2-4 cycles depending on pts' health status, in combination with Sintilimab (200mg, iv, d1) and regorafenib (80mg, po, d1-21) every 3 weeks for up to 6 months .

treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Aged over 18 years， men or women who are not pregnant；
• ECOG PS 0/1 evaluated 14 days before enrollment, and expected survival \>12 months after liver resection;
• Liver function: Child-Pugh score Class A or ≤7 Class B；
• Patients with histologically- or clinically-confirmed CRLM（TxNxM1）and CRS\>2；
• Patients had completely resected Primary lesions and liver metastases as well as no evidence of extrahepatic disease；
• No complications such as bleeding, jaundice, infection, abdominal pleural effusion, obstruction and perforation were observed within 7 days (including 7 days) before the screening. The subjects recovered well after surgery, the surgical incision healed well, the stitches were removed, and the drainage tube was removed;
• Preoperative chemoradiotherapy was limited to neoadjuvant or conversion therapy；
• Patients must have the ability to understand and voluntarily sign the informed consent, and must sign an informed consent before starting any specific procedure for the study；
• Patients were considered capable of complying with the study protocol；

You may not qualify if:

• Pre-treatment tumour tissue sample (if available). If tumour tissue is available, submit one formalin-fixed, paraffin-embedded (FFPE) tumour sample from a paraffin block (preferred), or approximately 10-15 slides containing unstained, freshly cut, serial sections, along with a relevant pathology report within 4 weeks of enrollment. If the FFPE samples described above are not available, any type of sample (including fine needle aspiration biopsy samples, cell mass samples \[e.g., samples from pleural effusion\] and lavage samples) may also be accepted. An associated pathology report should be provided with the sample. If tumour tissue is not available (e.g., exhausted due to past diagnostic tests), subjects are still eligible for study participation;
• Adequate haematological and organ function， based on the following laboratory results obtained during the 14 days prior to enrollment (unless otherwise stated) ： Absolute neutrophil count (ANC)≥1.5×10 9 /L (1500/μL)， without supported granulocyte colony-stimulating factor Lymphocyte count ≥0.5×10 9 /L (500/μL) Platelets ≥ 75 × 10 9 /L（75, 000/μL） Haemoglobin≥ 85 g/L, blood transfusions may be permitted to meet this criterion Aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP) ≤ 5 × upper limit of normal (ULN); Serum bilirubin≤ 3 × ULN Serum creatinine ≤ 1.5 × ULN or calculated creatinine clearance ≥50 mL/min (using Cockcroft-Gault formula) Serum albumin≥28 g/L（2.8 g/dL） INR or aPTT≤2 × ULN, or PT prolonged ≤ 3 s if patients did not receive anticoagulant therapy.
• Albuminuria \< 2+ tested by urinary cellulose (carried out within 14 days prior to initiation of treatment); Patients with baseline albuminuria ≥2+ should have their urine collected for 24 hours and must then confirm that albuminuria content within 24 hours is \< 1g.
• Any acute, clinically significant treatment-related toxicity (due to prior treatment) must have resolved to ≤ grade 1 prior to enrollment, except for hair loss;
• HIV antibody test results were negative at screening;
• Patients with active hepatitis B virus (HBV) infection: HBVDNA \< 2000IU/mL acquired within 28 days prior to enrollment, receiving anti-HBV therapy (in accordance with local standard care, such as Entecavir) for at least 7 days prior to enrollment and willing to continue treatment during the study period; Patients with active hepatitis C virus (HCV) infection: HCVRNA \< 2000IU/mL acquired within 28 days prior to enrollment, receiving anti-HCV therapy for at least 7 days prior to enrollment and willing to continue treatment during the study;
• Women of childbearing age must undergo a negative pregnancy test (βHCG) before treatment, and women of childbearing age and men (who have sex with women of childbearing age) must agree to use effective contraception uninterrupted during treatment and for six months after the last therapeutic dose was administered.
• Colorectal cancer with extrahepatic metastasis;
• Malignant abdominal effusion;
• There were postoperative complications such as abdominal effusion, pleural effusion, intestinal cavity perforation, bleeding and intestinal obstruction that needed treatment.
• History of soft meningitis
• Current or past autoimmune diseases or immunodeficiency, including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener's granuloma, Sjogren's syndrome, Guillain-Barre syndrome, or multiple sclerosis, with the following exceptions: Subjects who had a history of autoimmune-related hypothyroidism and were receiving thyroid hormone replacement therapy were eligible; Subjects with controlled type 1 diabetes receiving insulin therapy were eligible; Subjects with clinical manifestations of eczema, psoriasis, chronic lichenia simple, or vitiligo only (e.g., excluding subjects with psoriatic arthritis) are eligible if they meet all of the following criteria: 1. Skin rash area must be \< 10% body surface area 2. Good disease control at baseline with only inefficient topical glucocorticoid therapy. 3. No acute exacerbations requiring psoralen plus A-band ultraviolet radiation, methotrexate, retinoic acid, biologics, oral calcineurin inhibitors, or high-performance or oral glucocorticoid therapy have occurred in the previous 12 months;
• Idiopathic pulmonary fibrosis, institutionalized pneumonia (e.g., bronchiolitis obliterans), drug-induced or idiopathic pneumonia, or evidence of active pneumonia on a chest computed tomography (CT) scan during screening. Radiation pneumonia was present in the allowable area (fibrosis)
• Active TB disease
• Major cardiovascular disease (such as New York Heart Society Class II or worse heart disease, myocardial infarction, or cerebrovascular accident), unstable arrhythmia, or unstable angina in the 3 months prior to enrollment;

Sponsors & Collaborators

• Fudan University: lead

Study Sites (1)

Fudan University Shanghai Cancer Center

Shanghai, 200032, China

RECRUITING

MeSH Terms

Interventions

sintilimab; regorafenib

Central Study Contacts

Lu Wang, M.D.

CONTACT

+86-18121299357; sysucczyf@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Hepatic Surgery

Study Record Dates

• First Submitted: February 21, 2023
• First Posted: March 3, 2023
• Study Start: August 2, 2022
• Primary Completion: March 1, 2024
• Study Completion: March 1, 2025
• Last Updated: March 3, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)