Clinical Study of Fruquintinib Combined With Raltitrexed in the Treatment of Metastatic Colorectal Cancer

A Single-arm, Open, Multicenter Clinical Study of Fruquintinib Combined With Raltitrexed in the Treatment of Metastatic Colorectal Cancer

To evaluate the efficacy and safety of Fruquintinib combined with Raltitrexed in the treatment of metastatic colorectal cancer that progressed or could not be tolerated after previous fluorouracil, oxaliplatin, and irinotecan based therapy

Study Overview

• Status: Recruiting
• Conditions: Metastatic Colorectal Cancer
• Intervention / Treatment: Drug: Fruquintinib

Detailed Description

To evaluate the progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), overall survival (OS), and safety of Fruquintinib combined with Raltitrexed in 30 patients with metastatic colorectal cancer who had progressed or could not tolerate fluorouracil, oxaliplatin, and irinotecan based therapy.

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Xiaodong Peng, Director; Phone Number: 0086-457-079186427246; Email: pxddhbb@163.com

Study Locations

• China
  • Jiangxi
    • Nanchang, Jiangxi, China
      • Recruiting
      • The First Affiliated Hospital of NanChang University
      • Contact: Xiaodong Peng; Phone Number: pxddhbb@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Have fully understood the study and voluntarily signed the informed consent;
2. Age ≥18 years old, gender unlimited;
3. Advanced metastatic colorectal adenocarcinoma confirmed by histopathology;

4. The patient progressed or was intolerant after receiving at least previous standard therapy containing fluorouracil, oxaliplatin, and irinotecan.

   • Each first-line treatment must include one or more chemotherapeutic agents for a duration of ≥1 cycle;
   • Allow pre-adjuvant/neoadjuvant therapy. 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;
   • Prior chemotherapy combined with cetuximab or bevacizumab is permitted;
5. Have at least one measurable lesion (RECIST 1.1 standard);
6. Eastern Cooperative Oncology Group (ECOG) physical condition 0-1 score;
7. Expected survival ≥12 weeks;

8. The functions of vital organs during the first 14 days of enrollment meet the following requirements (the use of any blood components and cell growth factors during the first 14 days of enrollment is not allowed) :

   • Absolute neutrophil count ≥1.5×109/L;
   • Platelet ≥80×109/L;
   • Hemoglobin ≥8g/dL;
   • Total bilirubin < 1.5 × upper limit of normal（ULN）;
   • Alanine aminotransferase (ALT) and Aspartate aminotransferase (AST) < 2.5 × ULN (< 5 × ULN in patients with liver metastasis);
   • Serum creatinine ≤1 × ULN;
   • endogenous creatinine clearance > 50ml/min;
9. Women of childbearing age or men whose partners wish to have children need to take effective contraceptive measures.

Exclusion Criteria:

1. Previous treatment with Fruquintinib or other anti-vascular endothelial growth factor receptor (VEGFR) inhibitors such as Apatinib, Regorafenib, and Anlotinib;
2. Previous treatment with Raltitrexed;
3. Participated in other drug clinical trials and received at least one drug therapy within four weeks prior to enrollment or received other systemic anti-tumor therapy, including chemotherapy, signal transduction inhibitors, hormone therapy, and immunotherapy within four weeks prior to enrollment;
4. The patient currently has a disease or condition that affects drug absorption, or the patient cannot take Fruquintinib orally;
5. The patient currently has gastrointestinal diseases such as gastric and duodenal active ulcers, ulcerative colitis, or active bleeding from unresectable tumors, or other conditions determined by researchers that may cause gastrointestinal bleeding or perforation;
6. Patients with active bleeding or bleeding tendency;

7. History of severe cardiovascular and cerebrovascular diseases:

   • Cerebrovascular accident (excluding lacunar infarction, minor cerebral ischemia, or transient ischemic attack), myocardial infarction, unstable angina, and poorly controlled arrhythmias (including QTc interval ≥ 450ms for men and 470 ms for women) within 6 months prior to first administration of the study drug (QTc interval Fridericia) Formula calculation);
   • New York Heart Association (NYHA) Heart Function Rating > Grade II or left ventricular ejection fraction (LVEF) < 50%;
8. Have had other malignancies within the past 5 years, except basal cell or squamous cell carcinoma of the skin after radical surgery, or carcinoma in situ of the cervix;
9. Clinically uncontrolled active infections, such as acute pneumonia, active hepatitis B or C (hepatitis B virus infection regardless of drug control, hepatitis B virus DNA≥1×104 copies /mL or > 2000 IU/ml);
10. There is known to be symptomatic central nervous system metastasis and/or cancerous meningitis. Participants with previously treated brain metastases may participate in the trial if their condition is stable (no evidence of radiographic progression at least 4 weeks prior to initial administration of the trial treatment), repeated radiographic studies confirm no evidence of new brain metastases or enlargement of the original brain metastases, and no steroid therapy is required at least 14 days prior to initial administration of the trial treatment. This exception does not include cancerous meningitis, which should be excluded regardless of whether it is clinically stable;
11. Women who are pregnant (positive pregnancy test before medication) or breastfeeding;
12. The patient currently has hypertension that cannot be controlled by drugs, which is prescribed as: systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg after taking antihypertensive drugs;
13. Urine routine indicates urinary protein ≥2+, or 24-hour urinary protein volume > 1.0g;
14. The patients considered by the investigators to be unsuitable for inclusion in this study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Fruquintinib combined with Raltitrexed group; Fruquintinib combined with Raltitrexed therapy	Drug: Fruquintinib; Fruquintinib capsule is taken orally once a day, 5 mg each time, and taken for 2 weeks and stopped for 1 week, every 21 days (3 weeks) for a cycle. Raltitrexed: 3 mg/m2 intravenously, on the first day of each cycle, for a treatment cycle of 3 weeks. Combination treatment until toxicity becomes intolerable, disease progression, or death.; Other Names: Raltitrexed

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression free survival (PFS)	The time from enrollment to disease progression or death	From date of randomization until the date of first documented progression or date of death

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate (ORR)	Proportion of patients with complete or partial response	through study completion, an average of 1 year
Disease control rate (DCR)	Proportion of patients assessed as having a complete response, partial response, or stable disease	through study completion, an average of 1 year
Overall survival (OS)	Patients were enrolled until their death from any cause	Through study completion, an average of 1year
Security	Safety was evaluated by adverse reactions	Through study completion, an average of 1year

Collaborators and Investigators

• Sponsor: The First Affiliated Hospital of Nanchang University
• Investigators: Study Chair: Xiaodong Peng, Director, The First Affiliated Hospital of NanChang University

Study record dates

Study Major Dates

• Study Start (Actual): October 20, 2023
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): October 1, 2026

Study Registration Dates

• First Submitted: October 26, 2023
• First Submitted That Met QC Criteria: November 1, 2023
• First Posted (Actual): November 7, 2023

Study Record Updates

• Last Update Posted (Actual): November 7, 2023
• Last Update Submitted That Met QC Criteria: November 1, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: metastatic colorectal cancer; Fruquintinib; Raltitrexed
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Folic Acid Antagonists; Raltitrexed
• Other Study ID Numbers: HMPL-013-E1-C002

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No