Clinical trial NCT06269445: The Efficacy and Safety of Lcaritin Combined With Bevacizumab and FOLFIRI in Treatment of Liver Metastases From Colorectal Cancer
Official title: The Efficacy and Safety of Lcaritin Combined With Bevacizumab and FOLFIRI in Treatment of Liver Metastases From Colorectal Cancer: A Prospective, Single-arm Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Colorectal Cancer
Lead sponsor: Sir Run Run Shaw Hospital
Sponsor class: OTHER
First posted: 2024-02-21
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: To evaluate the efficacy and safety of the combination regimen of Icaritin with bevacizumab + FOLFIRI in patients with liver metastases from advanced colorectal cancer.

Detailed description: At present, second-line only targeting combined with chemotherapy is the main treatment option, and the choice of treatment modality is limited, with the immunotherapy rise of immunotherapy, the mode of combining immunotherapy on the basis of existing first- and second-line chemotherapy combined with targeting is also being actively explored, but no positive results of large-scale phase III clinical studies have been reported yet. Meanwhile, there is no solution to the the problem of pro-inflammatory factor release. Therefore, it is necessary to consider the combination of a drug with a better safety profile and target-immunity synergistic effect. A combination of drugs with better safety and target-immunity synergistic effect could be considered as a safer and more effective treatment option for patients with liver metastases from advanced colorectal cancer.

Eligibility criteria: Inclusion Criteria:

* 1). Age ≥ 18 years. 2).Patients with unresectable advanced metastatic colorectal cancer confirmed by clinical diagnostic criteria and/or histopathological or cytological examination. Metastases include, but are not limited to the liver.

  3). Presence of clearly measurable (RECIST 1.1 compliant) liver metastases on imaging assessment (unresectable by MDT assessment).

  4). Patients who have failed prior first-line systemic systemic therapy, including bevacizumab.

  5).ECOG PS score 0-1. 6). Have normal organ function and meet the following criteria on laboratory tests within 7 days prior to initiation of therapy:
  1. Haemoglobin level \> 80 g/L;
  2. Absolute neutrophil count (ANC) ≥ 1.5 x 109/L;
  3. Platelet count ≥50×10-9/L;
  4. Serum albumin ≥ 30 g/L;
  5. Total bilirubin ≤ 2 × upper limit of normal (ULN);
  6. Aspartate aminotransferase (AST), alanine aminotransferase (ALT) ≤ 5 × ULN;
  7. Alkaline phosphatase (ALP) ≤ 2.5 x ULN;
  8. creatinine ≤ 1.5 x ULN and creatinine clearance ≥ 50 ml/min. 7). Good swallowing function. 8). Coagulation function: international normalised ratio (INR) ≤ 1.5 x ULN or prothrombin time (PT)≤16s.

     9). Life expectancy ˃3 months. 10). Voluntary participation in this study and voluntary signing of informed consent.

     11). Men and women of gestational age must agree to use adequate contraception throughout the study and for 3 months after the end of treatment.

     Exclusion Criteria:
* 1). Pre-existing or coexisting other active malignant tumours (except for malignant tumours that have been curatively treated and have been free of malignancy that has received curative treatment and has been free of morbidity for more than 5 years or carcinoma in situ that can be cured by adequate treatment).

  2). Concomitant administration of modern Chinese medicinal preparations for antitumour and anti-tumour indications.

  3). Patients who have received chemotherapy or anti-vascular endothelial growth factor receptor (VEGF) therapy.

  4). Patients receiving systemic chemotherapy, hormonal therapy, immunotherapy, approved proteins/antibodies or any experimental drugs or treatments (30 days) or radiotherapy (within 14 days).

  5). Tumour invasion of large blood vessels. 6). Significant cardiovascular compromise within 12 months prior to the first dose of study drug: e.g., New York Heart Association (NYHA) Class II or higher. Stroke, myocardial infarction or cerebral haemorrhage, or arrhythmia associated with haemodynamic instability; Corrected QT (QTc) interval prolongation \>480ms.

  7). Any surgical procedure within the last 28 days. 8). Bleeding from ruptured oesophageal or gastric varices within the last 2 weeks, or unconfirmed severe varices and bleeding in the judgement of the investigator.

  9). Bleeding or thrombotic disorders or on thrombolytic therapy, coagulation disorders; study intervention Clinically significant haemoptysis or tumour bleeding of any cause within 2 weeks prior to first dose.

  10). Patients with uncontrolled epilepsy, history of central nervous system disease or psychiatric disorders, hypertension.

  11). Active autoimmune disease requiring systemic therapy within the past 2 years.

  12). Clinically significant ascites on physical examination that cannot be controlled medically.

  13). Pregnant or breastfeeding female patients, or those unwilling to use contraception during the trial.

  14). Known hypersensitivity to Icaritin, Bevacizumab and chemotherapeutic drug components.

  15). Suspect that it may cause contraindication to the use of the drug, or affect the reliability of the study results, or place the patient at a disease or condition that places the patient at high risk for treatment complications, or affects the patient's adherence to the trial medication.

  16). Vulnerable populations, including those with mental illness, cognitive impairment, critically ill patients, illiteracy, etc.

  17). Presence of other reasons that the investigator considers inappropriate for participation in this study.

Primary outcomes:
measure: Progression-free survival(PFS)
timeFrame: up to 5 years
Secondary outcomes:
measure: Objective remission rate (ORR)
timeFrame: up to 5 years
measure: Overall survival (OS)
timeFrame: up to 5 years
measure: Disease Control Rate (DCR)
timeFrame: up to 5 years
measure: Duration of ongoing remission (DOR)
timeFrame: up to 5 years
measure: TRAEs
timeFrame: up to 5 years
measure: Quality of life of the patients
timeFrame: up to 5 years
Other outcomes:
Locations:
city: Hangzhou
country: China
facility: Sir Run Run Shaw Hospital, Zhejiang University School of Medicine
state: Zhejiang
Study officials:
affiliation: Sir Run Run Shaw Hospital
name: Sheng Dai
role: PRINCIPAL_INVESTIGATOR
References: