Trial Title:
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
NCT ID:
NCT05753163
Condition:
Colorectal Liver Metastasis
Conditions: Official terms:
Neoplasm Metastasis
Liver Neoplasms
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Combination Product
Intervention name:
HAIC-FOLFOX combined with Sintilimab and Regorafenib
Description:
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 .
Arm group label:
treatment
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.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Aged over 18 years， men or women who are not pregnant；
2. ECOG PS 0/1 evaluated 14 days before enrollment, and expected survival >12 months
after liver resection;
3. Liver function: Child-Pugh score Class A or ≤7 Class B；
4. Patients with histologically- or clinically-confirmed CRLM（TxNxM1）and CRS>2；
5. Patients had completely resected Primary lesions and liver metastases as well as no
evidence of extrahepatic disease；
6. 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;
7. Preoperative chemoradiotherapy was limited to neoadjuvant or conversion therapy；
8. 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；
9. Patients were considered capable of complying with the study protocol；
10. No medical comorbidities that could interfere with chemotherapy and immunotherapy or
targeted therapy, see exclusion criteria；
11. 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;
12. 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.
13. Any acute, clinically significant treatment-related toxicity (due to prior
treatment) must have resolved to ≤ grade 1 prior to enrollment, except for hair
loss;
14. HIV antibody test results were negative at screening;
15. 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;
16. 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.
Exclusion Criteria:
1. Colorectal cancer with extrahepatic metastasis;
2. Malignant abdominal effusion;
3. There were postoperative complications such as abdominal effusion, pleural effusion,
intestinal cavity perforation, bleeding and intestinal obstruction that needed
treatment.
4. History of soft meningitis
5. 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;
6. 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)
7. Active TB disease
8. 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;
9. A history of congenital long QT syndrome or a corrected QT interval >500ms at
screening (calculated using Fridericia's method);
10. A history of uncorrected electrolyte disturbances such as serum potassium, calcium,
or magnesium
11. Received major surgery within 4 weeks prior to the enrollment (except for diagnosis)
or expected to require major surgery during the study period;
12. Malignancies other than CRC that have developed within 5 years prior to screening,
with the exception of those with a negligible risk of metastasis or death (e.g.,
5-year OS rate > 90%), such as adequately treated cervical carcinoma in situ,
non-melanoma skin cancer, localized prostate cancer, duct carcinoma in situ, or
stage I uterine cancer;
13. Severe infections, including but not limited to hospitalization due to infection,
bacteremia, or severe pneumonia complications, occurred in the 4 weeks prior to the
enrollment;
14. Therapeutic antibiotics were given orally or intravenously within 2 weeks prior to
the enrollment. Subjects who received prophylactic antibiotics (for example, to
prevent urinary tract infections or exacerbations of COPD) were eligible;
15. Previous allogeneic stem cell or solid organ transplantation;
16. Received live attenuated vaccine within 4 weeks prior to the enrollment, or expected
to receive such vaccine during sintilimab treatment or within 5 months after the
last dose;
17. With untreated or incompletely treated esophageal and/or gastric varicose veins
associated with bleeding or at high risk of bleeding. Prior to enrollment, subjects
must undergo ultrasound, CT, MRI, or liver elasticity tests, assess the size of all
varicose veins (small to large), and be treated according to local standard care.
Subjects who received the corresponding examination within 6 months prior to the
enrollment do not need to be re-examined;
18. Co-infection with HBV and HCV. Subjects with a history of HCV infection but negative
PCR results for HCV RNA are considered not infected with HCV;
19. Symptomatic, untreated, or progressive central nervous system (CNS) metastases.
Asymptomatic subjects whose CNS lesions have been treated are eligible as long as
they meet all of the following criteria: They must have measurable lesions outside
the CNS according to RECIST v1.1; Subjects had no history of intracranial or spinal
bleeding; Metastases are limited to the cerebellar or supratentorial regions (i.e.,
no midbrain, pontine, medullary, or spinal cord metastases); No evidence of progress
between completion of CNS oriented therapy and initiation of study therapy; Subjects
had not received stereotactic, whole brain radiation, and/or neurosurgical resection
within 28 days prior to the enrollment; There was no need for continuous use of
glucocorticoids to treat CNS disease. A steady dose of anticonvulsant therapy is
permitted. Asymptomatic subjects with newly detected CNS metastases at the time of
screening are eligible after radiotherapy or surgery, and no need for repeated
screening of brain scan results;
20. Refuse follow-up and participating in other clinical trials that may interfere with
this study;
21. Patients are not suitable for enrollment judged by investigators.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Fudan University Shanghai Cancer Center
Address:
City:
Shanghai
Zip:
200032
Country:
China
Status:
Recruiting
Contact:
Last name:
Lu Wang
Phone:
+8618121299357
Email:
w.lr@hotmail.com
Start date:
August 2, 2022
Completion date:
March 2025
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/NCT05753163
