Trial Title:
A Prospective Multi-centered Randomized Controlled Trial on Fruquintinib in Combination With HAIC in the Treatment of Liver Metastatic Colorectal Cancer After Failure of Second-line Systematic Therapy
NCT ID:
NCT05511051
Condition:
Colorectal Cancer
Conditions: Official terms:
Colorectal Neoplasms
Conditions: Keywords:
Third-line
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Fruquintinib
Description:
Fruquintinib
Arm group label:
Fruquintinib
Arm group label:
Fruquintinib + HAIC
Intervention type:
Drug
Intervention name:
HAIC
Description:
HAIC
Arm group label:
Fruquintinib + HAIC
Summary:
The current study is to investigate the safety and efficacy of fruquintinib combined with
HAIC in patients with advanced colorectal liver metastases who have failed second-line
systemic standard treatment, in order to provide more survival opportunities for the
second progression of advanced colorectal liver metastases.
Detailed description:
Among Chinese colorectal cancer patients, 43.8% had metastasis at the time of diagnosis,
of which liver metastasis accounted for 51.5%. In addition, it was reported that 10%-25%
of patients developed liver metastasis after radical resection of colorectal cancer, and
more than two-thirds of colorectal patients eventually developed liver metastasis.
Colorectal liver metastasis was reported to be the most important cause of death in
colorectal cancer patients.The median survival time of untreated liver metastases was
only 6.9 months, and the 5-year survival rate of unresectable patients was less than 5%,
and for unresectable colorectal liver metastasis, the median survival time could reach
30.9 months after comprehensive treatment.
Fruquintinib, a VEGFR 1/2/3 inhibitor, is one of the standard 3rd-line therapy for
colorectal cancer, which has already been approved and marketed in China. In phase III
FRESCO study, liver metastases subgroup showed that the median OS of fruquintinib group
was 8.61 months, which was 2.63 months longer than that of control group, reducing death
risk by 41%, with statistically significant P value.
Patients with large tumor burden mainly caused by liver metastasis and with insignificant
or refractory response to drug therapy, or patients who cannot tolerate systemic therapy,
can be combined with transcatheter arterial chemoembolization (HAI) or transcatheter
arterial chemoembolization (TACE) at appropriate time, which helps to prolong the
progression-free time and overall survival.
The current study is to investigate the safety and efficacy of fruquintinib combined with
HAIC in patients with advanced colorectal liver metastases who have failed second-line
systemic standard treatment, in order to provide more survival opportunities for the
second progression of advanced colorectal liver metastases.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Fully understand the study and voluntarily sign the informed consent form;
2. Age ≥ 18 years;
3. Patients with unresectable colorectal liver metastases who have failed standard
second-line systemic therapy, who have not previously received HAIC therapy, and
have not received third-line standard targeted agents (regorafenib or fruquintinib
or trifluridine tipiracil (TAS-102);
4. Definition of liver metastases: at least 1 measurable liver metastasis lesion (based
on RECIST 1.1); if the liver metastases are single, the tumor is > 5 cm; if multiple
tumors, it needs to be greater than or equal to 4, of which at least 1 exceeds 3 cm;
5. PFS > 4 months from last dose of oxaliplatin with FOLFOX regimen
6. Child-Pugh classification of liver function: A;
7. ECOG performance status 0-1, and no deterioration within 7 days;
8. BMI ≥ 18;
9. Expected survival ≥ 3 months;
10. Vital organs function in accordance with the following requirements (any blood
components and cell growth factors are not allowed within 14 days before
enrollment):
- Absolute neutrophil count ≥ 1.5 × 109/L and white blood cells ≥ 4.0 × 109/L;
- Platelets ≥ 100 × 109/L;
- Hemoglobin ≥ 90 g/L;
- Total bilirubin TBIL ≤ 1.5 times ULN;
- ALT and AST ≤ 5 times ULN;
- Urea nitrogen/urea nitrogen (BUN) and creatinine (Cr) ≤ 1.5 × ULN (and
creatinine clearance (CCr) ≥ 50 mL/min);
- Left ventricular ejection fraction (LVEF) ≥ 50%;
- Fridericia-corrected QT interval (QTcF) < 470 milliseconds.
- INR ≤ 1.5 × ULN, APTT ≤ 1.5 × ULN.
11. women of childbearing age need to take effective contraceptive measures;
12. good compliance and cooperation with follow-up.
Exclusion Criteria:
1. Unable to comply with the study protocol or study procedures;
2. Pregnant or breastfeeding women;
3. Any factor affecting oral administration;
4. Evidence of central nervous system metastases;
5. Concurrent with any of the following: uncontrolled hypertension, coronary artery
disease, arrhythmia, and heart failure;
6. Alcohol or drug abuse within 4 weeks after the last clinical trial;
7. Previous VEGFR inhibition therapy;
8. Uncontrolled severe concurrent infection resulting in disability;
9. Proteinuria ≥ 2 + (1.0 g/24 h);
10. Evidence or history of bleeding tendency within 2 months prior to enrollment,
regardless of seriousness;
11. Arterial/venous thromboembolic events, such as cerebrovascular accidents (including
transient ischemic attack), within 12 months before the first treatment;
12. Acute myocardial infarction, acute coronary syndrome or CABG within 6 months before
the first treatment;
13. Fractures or wounds that have not been cured for a long time;
14. coagulopathy, bleeding tendency or receiving anticoagulant therapy;
15. Inactivated vaccines within 4 weeks prior to enrollment or possible during the
study;
16. Patients with other malignant tumors within 5 years before enrollment, except for
basal cell or squamous cell carcinoma of the skin after radical resection, or
cervical carcinoma in situ;
17. Active autoimmune diseases or history of autoimmune diseases within 4 weeks before
enrollment;
18. Previous allogeneic bone marrow transplantation or organ transplantation;
19. Subjects who are allergic to the study drug or any of its adjuvant preparations;
20. Electrolyte abnormalities judged clinically significant by the investigator;
21. Known human immunodeficiency virus (HIV) infection. Known history of clinically
significant liver disease, including viral hepatitis [known hepatitis B virus (HBV)
carriers must have excluded active HBV infection, ie, positive HBV DNA (> 1 × 104
copies/mL or > 2000 IU/mL); known hepatitis C virus (HCV) infection and positive HCV
RNA (> 1 × 103 copies/mL);
22. Unresolved toxicities above CTCAE v5.0 grade 1 due to any prior anticancer therapy,
excluding alopecia, lymphopenia, and oxaliplatin-induced neurotoxicity ≤ grade 2;
23. Received blood transfusion therapy, blood products and hematopoietic factors, such
as albumin and granulocyte colony-stimulating factor (G-CSF), within 28 days before
enrollment;
24. with brain metastases, or with severe malignant pleural effusion and ascites;
25. Any other diseases, clinically significant metabolic abnormalities, physical
examination abnormalities or laboratory abnormalities, according to the investigator
's judgment, there is reason to suspect that the patient has a disease or condition
that is not suitable for the use of the study drug (such as having seizures and
requiring treatment), or will affect the interpretation of the study results, or put
the patient at high risk;
26. Patients who are considered unsuitable for inclusion in this study by the
investigator.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Cancer Institute and Hospital, Chinese Academy of Medical Sciences
Address:
City:
Beijing
Country:
China
Status:
Recruiting
Contact:
Last name:
Yue Han
Phone:
+86-13511021629
Email:
doctorhan@163.com
Facility:
Name:
Dalian Medial University Affiliated Second Hospital
Address:
City:
Dalian
Country:
China
Status:
Not yet recruiting
Contact:
Last name:
Jinghua Sun
Facility:
Name:
People's Hospital of Inner Mongolia
Address:
City:
Hohhot
Country:
China
Status:
Not yet recruiting
Contact:
Last name:
Liying Xue
Start date:
February 1, 2022
Completion date:
December 31, 2024
Lead sponsor:
Agency:
Cancer Institute and Hospital, Chinese Academy of Medical Sciences
Agency class:
Other
Collaborator:
Agency:
Hutchison Medipharma Limited
Agency class:
Industry
Source:
Cancer Institute and Hospital, Chinese Academy of Medical Sciences
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05511051