Trial Title:
Fruquintinib Combined With Chemotherapy as Third-line /Third-line+ Treatment in Advanced Colorectal Cancer
NCT ID:
NCT05928312
Condition:
Advanced Colorectal Cancer
Conditions: Official terms:
Colorectal Neoplasms
Oxaliplatin
Irinotecan
Study type:
Interventional
Study phase:
N/A
Overall status:
Not yet recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Fruquintinib Combined With Chemotherapy
Description:
1.Security introduction period:
[1] Safety introduction period (N=6), fruquintinib combined with three-week regimen:
1. Fruquintinib: Three-week regimen of combined chemotherapy: 4mg/d, orally, once a
day, taking the drug for 2 weeks and stopping the drug for 1 week, 3 weeks as a
treatment cycle.
[2] Safety introduction period (N=6), fruquintinib combined 2-week regimen:
1. Fruquintinib: two-week combination chemotherapy regimen: 4mg/d, orally, once a day,
taking the drug for 3 weeks and stopping the drug for 1 week, 4 weeks as a treatment
cycle.
2. Dose expansion phase design(N=60) Cohort 1 (30 patients) : Fruquintinib combined
with oxaliplatin. Cohort 2 (30 patients) : Fruquintinib combined with irinotecan .
Arm group label:
Advanced CRC
Other name:
Fruquintinib oxaliplatin irinotecan
Summary:
To explore the efficacy and safety of fruquintinib combined with chemotherapy as
third-line/third-line+ Treatment in advanced metastatic colorectal cancer
Detailed description:
Due to the limited efficacy of third-line treatment, the previously effective
chemotherapy regimen is a new treatment mode. RE-OPEN, RE-OX and a Korean study confirmed
that mCRC patients who had previously been effectively treated with oxaliplatin were
retreated with oxaliplatin on the third line to help them achieve OS for 14.5 to 18.5
months. At the same time, a phase III randomized SUNLIGHT study showed good efficacy at
the ASCO-GI Congress in 2023. The above studies show that the regimen of antivascular
drugs combined with chemotherapy has a tendency to improve the survival of patients with
third-line advanced colorectal cancer.
In order to further improve the efficacy of fruquintinib, we conducted a clinical study
of fruquintinib combined with chemotherapy to observe the efficacy and safety of
Third-line/Third-line+ treatment of advanced colorectal cancer, and to provide a more
effective treatment plan for third-line and above treatment for advanced colorectal
cancer patients.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Have fully understood the study and voluntarily signed the informed consent
2. Age ≥18 years old, male or female
3. Advanced metastatic colorectal adenocarcinoma confirmed by histopathology
4. The best efficacy evaluation of first-line chemotherapy (mFOLFOX6, XELOX, or
FOLFIRI) in previous patients must be partial response (PR) or above or
progression-free survival (PFS) ≥1 year, with a first-line drug withdrawal interval
of more than 1 year. Pre-adjuvant/neoadjuvant therapy is allowed. If recurrence or
metastasis occurs during or within 6 months after completion of adjuvant/neoadjuvant
therapy, adjuvant/neoadjuvant therapy is considered a failure of first-line
chemotherapy for advanced disease
5. The patient has failed at least previous second-line treatment，The use of Cetuximab
(KRAS and Braf wild type) and bevacizumab in previous anti-tumor regiments is
required，Prior treatment with regorafenib or TAS-102 is permitted
6. ECOG status 0-2 points
7. Expected survival ≥12 weeks
8. Have at least one measurable lesion (RECIST version 1.1)
9. Inadequate bone marrow reserve or organ function, as demonstrated by any of the
following laboratory values: Absolute neutrophil count (ANC) ≥1.5×109/L Platelet
count ≥80×109 / L Hemoglobin≥80 g/L（<8 g/dL） Serum albumin ≥3g/dL Alanine
aminotransferase <2.5 × upper limit of normal (ULN) if no demonstrable liver
metastases or <5 × ULN in the presence of liver metastases. Aspartate
aminotransferase (AST) <2.5 × ULN if no demonstrable liver metastases or < 5 × ULN
in the presence of liver metastases. Total bilirubin (TBL)<1.5 × ULN Creatinine≤ 1.5
× ULN concurrent with creatinine clearance ≤50 mL/min (measured or calculated by the
Cockcroft-Gault equation) confirmation of creatinine clearance is only required when
creatinine is ≤1.5 × ULN.
10. Fertile male or female patients voluntarily used effective contraceptive methods,
such as double barrier methods, condoms, oral or injectable contraceptives,
intrauterine devices, etc., during the study period and within 6 months of the last
study dose. All female patients will be considered fertile unless they have
undergone natural menopause, artificial menopause, or sterilization (such as
hysterectomy, bilateral adnexectomy, or irradiation of radioactive ovaries).
11. Good compliance, cooperate with follow-up.
Exclusion Criteria:
- 1: Patients with known dMMR or MSI-H colorectal cancer who have not previously used
anti-PD-1 or PD-L1 inhibitors
2: Previously received small molecule targeted drug therapy with fuquinitinib
3: Symptomatic brain or meningeal metastases (except those with brain metastases
that have undergone local radiotherapy or surgery for more than 6 months and whose
disease control is stable)
4: Severe infection (such as intravenous infusion of antibiotics, antifungals, or
antiviral drugs) within 4 weeks prior to treatment, or unexplained fever > 38.5 ° C
during screening/first administration
5: Have high blood pressure that is not well controlled by antihypertensive
medications (systolic blood pressure ≥150 mmHg or diastolic blood pressure ≥100
mmHg)
6: Obvious clinical bleeding symptoms or obvious bleeding tendency within 3 months
prior to treatment (bleeding > 30 mL within 3 months, hematemesis, black stool,
blood in the stool), hemoptysis (> 5 mL of fresh blood within 4 weeks), etc. Or
treatment of arterial venous thrombosis events within the preceding 6 months, such
as cerebrovascular accidents (including transient ischemic attack, cerebral
hemorrhage, cerebral infarction), deep vein thrombosis, and pulmonary embolism
7: Long-term anticoagulant therapy with warfarin or heparin, or long-term
antiplatelet therapy (aspirin ≥300 mg/day or clopidogrel ≥75 mg/day) is required
8: During screening, it was found that the tumor invaded large vascular structures,
such as pulmonary artery, superior vena cava or inferior vena cava, etc., and the
researchers judged that there was a risk of major bleeding
9: The patient currently has gastrointestinal diseases such as active gastric and
duodenal ulcers, ulcerative colitis, or active bleeding from unresectosed tumors, or
other conditions determined by researchers that may cause gastrointestinal bleeding
or perforation .Active heart disease, including myocardial infarction,
severe/unstable angina, occurs 6 months before treatment. Left ventricular ejection
fraction <50% by echocardiography showed poor arrhythmia control.
10: Patients with other malignant tumors (except cured basal cell carcinoma of the
skin and carcinoma in situ of the cervix) in the past 5 years or at the same time
11: Known allergy to the investigational drug or any of its excipients
12: Active or uncontrolled severe infection
1. Known human immunodeficiency virus (HIV) infection
2. Known history of clinically significant liver disease, including viral
hepatitis [active HBV infection, i.e., positive HBV DNA (>1×104 copies /mL or
>2000 IU/ml) must be excluded for known hepatitis B virus (HBV) carriers
3. Known hepatitis C virus infection (HCV) and HCV RNA positive (>1×103 copies
/mL), or other hepatitis, cirrhosis]
13. Any other medical condition, clinically significant metabolic abnormality,
physical abnormality or laboratory abnormality, in which, in the investigator's
judgment, there is reason to suspect that the patient has a medical condition
or condition that is not suitable for the use of the investigational drug (such
as having seizures and requiring treatment), or which would affect the
interpretation of the study results or place the patient at high risk
14. Urine routine indicated urinary protein ≥2+, and 24-hour urinary protein
quantity >1.0g.
15. Incomplete healing of skin wounds, surgical sites, trauma sites, severe mucosal
ulcers or fractures
16. Stroke events and/or transient cerebral ischemia occurred within 12 months
prior to enrollment
17. The patient has any current disease or condition that affects drug absorption,
or the patient is unable to take fuquintinib orally
18. Women who are pregnant (positive pregnancy test before medication) or
breastfeeding
19. The patients considered by the investigators to be unsuitable for inclusion in
this study.
Gender:
All
Minimum age:
18 Years
Maximum age:
75 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Zhejiang Cancer Institute & Hospital
Address:
City:
Hangzhou
Country:
China
Contact:
Last name:
Wangxia Lv
Phone:
13757141026
Email:
lvwangxia@163.com
Investigator:
Last name:
HaiJun Zhong
Email:
Principal Investigator
Investigator:
Last name:
Meiqin Yuan
Email:
Sub-Investigator
Investigator:
Last name:
Bixia Liu
Email:
Sub-Investigator
Investigator:
Last name:
Zhong Shi
Email:
Sub-Investigator
Investigator:
Last name:
Tingting Feng
Email:
Sub-Investigator
Investigator:
Last name:
Junchi Cheng
Email:
Sub-Investigator
Start date:
August 28, 2023
Completion date:
June 1, 2026
Lead sponsor:
Agency:
Zhejiang Cancer Hospital
Agency class:
Other
Source:
Zhejiang Cancer Hospital
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05928312
