TAS-102 in Combination With Regorafenib or Fruquintinib for Third-line and Above Advanced Colorectal Cancer

Single-arm, Multicentre Real-world Observational Study of TAS-102 in Combination With Regorafenib or Fruquintinib for Third-line and Above Advanced Colorectal Cancer

This is a single-arm, multicentre real-world observational study of TAS-102 in combination with regorafenib or fruquintinib for third-line and above advanced colorectal cancer.

Study Overview

• Status: Not yet recruiting
• Conditions: Fruquintinib; Regorafenib; Gastrointestinal Tumours; TAS 102
• Intervention / Treatment: Drug: regorafenib; Drug: fruquintinib

Detailed Description

This is a single-arm, multicentre real-world observational study of TAS-102 in combination with regorafenib or fruquintinib for third-line and above advanced colorectal cancer.The purpose of the study is to evaluate the efficacy and safety of TAS-102 in combination with a regimen of regorafenib or fruquintinib for the treatment of advanced colorectal cancer in the third line and above.

• Study Type: Observational
• Enrollment (Estimated): 45

Contacts and Locations

• Study Contact: Name: Yunpeng Liu, PhD; Phone Number: 86-24-83282312; Email: cmu_trial@163.com
• Study Contact Backup: Name: Ling Xu, PhD; Email: cmuxuling@163.com

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

Male or female patients between the ages of 18-75 years

Description

Inclusion Criteria:

1. Male or female patients between the ages of 18-75 years;
2. Patients with colorectal cancer diagnosed by histology or cytology;
3. Patients with metastatic colorectal cancer who have failed two or more standard therapies; patients are permitted to have received prior chemotherapy with fluorouracil, oxaliplatin, irinotecan, and other regimens, patients are permitted to receive EGFR and/or VEGF inhibitors, and patients are permitted to have received prior immunotherapy;
4. Have at least one measurable lesion according to the solid tumour efficacy evaluation criteria RECIST version 1.1; the measurable lesion should not have received local treatment such as radiotherapy (lesions located within the area of previous radiotherapy may also be selected as target lesions if progression is confirmed to have occurred and meets the RECIST 1.1 criteria);
5. ECOG PS score: 0 to 1; expected survival more than 3 months;
6. Oral medication is available;
7. have adequate organ and bone marrow function, i.e., meet the following criteria:

(1) Criteria for routine blood tests need to be met: Haemoglobin level (HB) ≥ 90 g/L (no transfusion within 28 days); Absolute neutrophil count (ANC) ≥ 1.5 x 109/L; Platelet count (PLT) ≥ 100×109/L. (2) Biochemical tests need to meet the following criteria: Serum total bilirubin (TBIL) ≤ 1.5 times the upper limit of normal (ULN) ; ALT and AST ≤ 2.5 ULN (ALT and AST ≤ 5 ULN if liver metastases are present); Cr ≤ 1.5 ULN or creatinine clearance (CCr) ≥ 60 ml/min; (Cockcroft-Gault formula) (3) Adequate coagulation function, defined as International Normalised Ratio (INR) or Prothrombin Time (PT) ≤ 1.5 times ULN; 8) Pregnant or breastfeeding patients: 1) Females and males of childbearing potential must agree to use adequate contraception prior to entering the programme until at least 8 weeks after the last dose of study drug. The Investigator or designee is required to advise subjects on how to achieve adequate contraception. Appropriate contraception is defined in the study as any medically recommended method (or combination of methods) based on standard treatment 2) Women of childbearing age must have a negative serum or urine pregnancy test confirmed within 7 days prior to initiating treatment and must agree to record a negative result prior to entering the study.

Exclusion Criteria:

- study:

1. Patients with abnormal coagulation or a tendency to gastrointestinal bleeding on thrombolytic or anticoagulant medication, including active peptic ulcers with fecal occult blood++, vomiting blood or black stools within 3 months.
2. Prior or concurrent cancers with a primary site or histology different from CRC within the year of enrolment, with the exception of cured in situ cervical cancer, non-melanoma skin cancers, and superficial bladder tumours:staging Ta, Tis and T1 .
3. Arterial or venous thrombotic or embolic events, such as cerebrovascular accidents (including transient ischaemic attacks), deep vein thrombosis, or pulmonary embolism (except for appropriately treated catheter-associated venous thrombosis occurring more than 1 month after initiation of therapy), have occurred within 6 months prior to the start of treatment.
4. Major surgery, biopsy or significant traumatic injury within 28 days prior to the start of investigational therapy.
5. Unhealed wounds, ulcers, or fractures.
6. Patients with brain metastases and/or carcinomatous meningitis.
7. Congestive heart failure >New York Heart Association (NYHA) class 2.
8. Unstable angina (angina at rest), new onset angina (within the last 3 months). Myocardial infarction within 6 months prior to the start of treatment.
9. Arrhythmia requiring antiarrhythmic therapy (beta-blockers or digoxin permitted). Uncontrolled hypertension. (Systolic blood pressure > 150 mmHg or diastolic blood pressure > 90 mmHg despite optimal medical therapy).
10. Patients with pheochromocytoma
11. Pleural effusion or ascites causing respiratory restriction (≥ CTCAE grade 2 dyspnoea)
12. Active infection >NCI CTCAE2 level
13. interstitial lung disease with signs and symptoms at the time of informed consent
14. known hypersensitivity to any of the drugs in the study, to drugs of the same class as the study drug, or to excipients in dosage forms
15. use of CYP3A4 inhibitors or inducers
16. Participation in another clinical trial within 4 weeks prior to enrolment and receipt of the investigational drug and any concomitant therapy containing the investigational drug
17. have received radiotherapy within 4 weeks prior to enrolment and the lesion under observation in this study is in the target area of radiotherapy
18. Subjects with active tuberculosis (TB) who are receiving anti-tuberculosis treatment or have received anti-tuberculosis treatment within one year prior to screening
19. Subjects with comorbidities requiring long-term treatment with immunosuppressive drugs or systemic or topical corticosteroids at immunosuppressive doses (>10mg/day of prednisone or other equipotent hormones).
20. Received any anti-infective vaccine (e.g., influenza vaccine, varicella vaccine, neocoronavirus vaccine, etc.) within 4 weeks prior to enrolment.
21. Pregnancy or breastfeeding
22. Persistent proteinuria >3.5 g/24 hours by measurement of urine protein-creatinine ratio (grade 3, NCI-CTCAE version 5.0) in random urine samples.
23. Human immunodeficiency virus (HIV) positive
24. Hepatitis B virus surface antigen (HBsAg) positive and HBV DNA copy number positive (quantitative test ≥1000 cps/ml)
25. Positive blood test for chronic hepatitis C (HCV antibody positive)
26. renal failure requiring haemodialysis or peritoneal dialysis
27. Dehydration ≥ CTCAE Version 5.0 Level 1
28. Persons who are legally incompetent.
29. Any other clinically significant disease or condition that, in the opinion of the investigator, may affect adherence to the protocol, or the signing of the Informed Consent Form (ICF) by the subject, or make participation in this clinical trial inappropriate.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
TAS-102 in combination with regorafenib; (TAS102): Trifluridine tepipiridine tablets 35 mg/m2 twice a day, D1-5, D15-D19, 28 days as a cycle; (TKI: regorafenib: regorafenib capsules administered at a dose of 80 mg (2 tablets, each containing 40 mg regorafenib) once daily for a 28-day cycle)	Drug: regorafenib; (TAS102): Trifluridine tepipiridine tablets 35 mg/m2 twice a day, D1-5, D15-D19, 28 days as a cycle; (TKI: regorafenib: regorafenib capsules administered at a dose of 80 mg (2 tablets, each containing 40 mg regorafenib) once daily for a 28-day cycle); Other Names: baiwange
TAS-102 in combination with fruquintinib; TAS102: Trifluridine tepipiridine tablets 35 mg/m2 twice a day, D1-5, D15-D19, 28 days as a cycle; Fruquintinib: a dose of 3mg/dose administered orally once daily, continuously for 28 days as a cycle.	Drug: fruquintinib; TAS102: Trifluridine tepipiridine tablets 35 mg/m2 twice a day, D1-5, D15-D19, 28 days as a cycle; or Fruquintinib: a dose of 3mg/dose administered orally once daily, continuously for 28 days as a cycle.; Other Names: elunate

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free Survival (PFS)	PFS, defined as the time from randomization to the first occurrence of disease progression as determined by the investigator with use of RECIST v1.1 or death from any cause, whichever occurs first.	one year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR)	ORR, determined using RECIST v1.1, defined as best overall response (CR or PR) across all assessment time points during the period from enrolment to termination of trial treatment.	one year
Disease Control Rate (DCR)	Determined using RECIST v1.1 criteria.	one year
Incidence and severity of adverse events (AE) and serious adverse events (SAE)	Incidence, nature, and severity of adverse events graded according to the NCI CTCAE v5.0.	two years

Collaborators and Investigators

• Sponsor: China Medical University, China
• Investigators: Principal Investigator: Yunpeng Liu, PhD, First Hospital of China Medical University

Study record dates

Study Major Dates

• Study Start (Estimated): September 1, 2023
• Primary Completion (Estimated): June 1, 2024
• Study Completion (Estimated): June 1, 2025

Study Registration Dates

• First Submitted: August 7, 2023
• First Submitted That Met QC Criteria: August 7, 2023
• First Posted (Actual): August 15, 2023

Study Record Updates

• Last Update Posted (Actual): August 15, 2023
• Last Update Submitted That Met QC Criteria: August 7, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms
• Other Study ID Numbers: PRAY

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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