Fruquintinib Combined With Chemotherapy as Third-line /Third-line+ Treatment in Advanced Colorectal Cancer

NCT05928312 | Not Yet Recruiting

• 1 other identifier: HMPL-013-FLAG-C127
• Study Type: interventional
• Target: 72
• Locations: 1 country
• Sites: 1

Brief Summary

To explore the efficacy and safety of fruquintinib combined with chemotherapy as third-line/third-line+ Treatment in advanced metastatic colorectal cancer

Conditions

Advanced Colorectal Cancer

Outcome Measures

Primary Outcomes (2)

• Dose-limiting toxicity(DLT)

  Usually refers to the highest dose at which a subject's probability of developing DLT does not exceed the probability of target toxicity during the regime-specified DLT observation period.

  up to 12 months

• Objective response rate (ORR)

  CR + PR rate according to the RECIST version 1.1 guidelines.

  up to 12 months

Secondary Outcomes (3)

• Progression Free Survival (PFS)

  up to 12 months

• Overall survival time

  up to 36 months

• Assess the anti-tumor activity:DCR

  up to 12 months

Study Arms (1)

Advanced CRC

EXPERIMENTAL

Patients with Advanced CRC were given Fruquintinib Combine With Chemotherapy.

Drug: Fruquintinib Combined With Chemotherapy

Interventions

Fruquintinib Combined With Chemotherapy DRUG

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 .

Also known as: Fruquintinib oxaliplatin irinotecan

Advanced CRC

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Have fully understood the study and voluntarily signed the informed consent
• Age ≥18 years old, male or female
• Advanced metastatic colorectal adenocarcinoma confirmed by histopathology
• 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
• 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
• ECOG status 0-2 points
• Expected survival ≥12 weeks
• Have at least one measurable lesion (RECIST version 1.1)
• 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.
• 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).
• Good compliance, cooperate with follow-up.

You may not qualify if:

• : Patients with known dMMR or MSI-H colorectal cancer who have not previously used anti-PD-1 or PD-L1 inhibitors
• : Previously received small molecule targeted drug therapy with fuquinitinib
• : 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)
• : 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
• : Have high blood pressure that is not well controlled by antihypertensive medications (systolic blood pressure ≥150 mmHg or diastolic blood pressure ≥100 mmHg)
• : 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
• : Long-term anticoagulant therapy with warfarin or heparin, or long-term antiplatelet therapy (aspirin ≥300 mg/day or clopidogrel ≥75 mg/day) is required
• : 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
• : 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.
• : 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
• : Known allergy to the investigational drug or any of its excipients
• : Active or uncontrolled severe infection
• Known human immunodeficiency virus (HIV) infection
• Known history of clinically significant liver disease, including viral hepatitis \[active HBV infection, i.e., positive HBV DNA (\>1×104 copies /mL or \>2000 IU/ml) must be excluded for known hepatitis B virus (HBV) carriers
• Known hepatitis C virus infection (HCV) and HCV RNA positive (\>1×103 copies /mL), or other hepatitis, cirrhosis\]

Sponsors & Collaborators

• Zhejiang Cancer Hospital: lead

Study Sites (1)

Zhejiang Cancer Institute & Hospital

Hangzhou, Zhejing, China

Location

MeSH Terms

Interventions

Drug Therapy

Intervention Hierarchy (Ancestors)

Therapeutics

Study Officials

• Wangxia Lv

  Zhejiang Cancer Institute & Hospital

  STUDY CHAIR

Central Study Contacts

Wangxia Lv

CONTACT

13757141026; lvwangxia@163.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: June 19, 2023
• First Posted: July 3, 2023
• Study Start: August 28, 2023
• Primary Completion: June 28, 2025
• Study Completion (Estimated): June 1, 2026
• Last Updated: July 20, 2023

Record last verified: 2023-07

Locations

CN (1)