Lonsurf® (Trifluridine/Tipiracil) Plus Chemotherapy in Metastatic Colorectal Cancer Prospective Study in Taiwan

Not Applicable

Recruiting

• Conditions: Metastatic Colorectal Cancer
• Interventions: Drug: Trifluridine/tipiracil

• Registration Number: NCT06495463
• Lead Sponsor: Chang Gung Memorial Hospital

Brief Summary

Primary Endpoint : To evaluate the Disease control rate (DCR)

Secondary Endpoints:

To evaluate the Progression-free survival (PFS), Overall survival(OS) and Safety profile

Detailed Description

70 Per-protocol patients Plan to recruit 70 evaluable patients (With expected dropout rate of 22%, the sample size would be 90 subjects.) Simon's two-stage design (Simon, 1989) will be used. The null hypothesis that the true response rate is 0.45 will be tested against a one-sided alternative. In the first stage, 42 patients will be accrued. If there are 19 or fewer responses in these 42 patients, the study will be stopped. Otherwise, 28 additional patients will be accrued for a total of 70. The null hypothesis will be rejected if 39 or more responses are observed in 70 patients. This design yields a type I error rate of 0.05 and power of 0.8 when the true response rate is 0.6.

Study Timeline

• Study Start: 2022-03-19
• Status Verified: 2024-03
• Study First Submitted: 2024-06-27
• Study First Submitted QC: 2024-07-03
• Last Update Submitted: 2024-07-03
• Study First Posted: 2024-07-10
• Last Update Posted: 2024-07-10
• Primary Completion: 2024-08-31
• Study Completion: 2024-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 110

Inclusion Criteria

1. Histologically or cytologically confirmed adenocarcinoma of the metastatic colorectal cancer;
2. Previously treated with fluorouracil-, oxaliplatin-, and irinotecan-based chemotherapy, and anti-vascular endothelial growth factor (anti-VEGF) biological therapy;
3. The RAS wild-type patients need to receive anti-EGFR therapy;
4. Presence of at least one measurable tumor lesion which is defined as lesion that can be measured in at least one dimension (longest diameter) with a minimum size of : 10mm by CT scan, MRI and PET-CT(no less than double the slice thickness and a minimum of 10mm)(according to RECIST guideline version 1.1);
5. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0, 1 or 2;
6. Investigators prescribe Lonsurf® for metastatic colorectal cancer patients who had prior treatment with Anti-VEGF and Anti-EGFR agent on routine basis. Depending on RAS status, patients with RAS mutant receive Lonsurf® as 3rd line treatment, those with RAS wild type receive Lonsurf® as 3rd/4th line treatment;
7. Patients received either oxaliplatin or irinotecan.

Exclusion Criteria

1. Patients previously received Lonsurf® (Trifluridine／Tipiracil) or regorafenib;
2. With active central nervous system (CNS) metastasis (indicated by clinical symptoms, cerebral edema, steroid requirement, or progressive growth);
3. With clinically significant gastrointestinal hemorrhage;
4. Previous or current systemic malignancy with the exception of curatively treated non-melanoma skin cancer or cervical carcinoma in situ, unless there has been a disease-free interval of at least 5 years;
5. The patient at high risk from treatment complications including but not limited to symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia, uncontrolled diabetes, liver or renal failure and psychiatric illness or social situation that would preclude study compliance;
6. Active infection.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
trifluridine / tipiracil + Chemotherapy	Trifluridine/tipiracil	trifluridine / tipiracil 35 mg/m2 PO twice daily on days 1-5 and day 6-14 off combination with chemotherapy (choose one) : oxaliplatin 85mg/m2 IV on day 1 every 14 days or irinotecan 100mg/m2 IV on day 1 every 14 days.

Primary Outcome Measures

Name	Time	Method
Disease control rate (DCR)	Tumor response will be judged according to RECIST v 1.1 criteria within every 8 weeks(± 2 week) in treatment period. The evaluation period is up to 24 months from the date of ICF is signed to first recorded progress or death whichever occurs first.	The endpoints Disease Control Rate (DCR) is defined as the proportion of patients in whom the best overall response is determined as complete response (CR), partial response (PR) or stable disease (SD).

Secondary Outcome Measures

Name	Time	Method
Overall survival(OS)	The evaluation period is up to 48 months from the date of ICF is signed to the date of death.	Overall survival (OS) is defined from the first treatment of Lonsurf® to death.
Safety profile	The evaluation period is up to 24 months from all adverse events occurring between the first drug intake and 30 days (inclusive) after the last administration of trial medication will be collected.	All adverse events (AEs) will be summarized and listed. All adverse events occurring between the first drug intake and 30 days (inclusive) after the last administration of trial medication will be collected, and graded according to the common terminology criteria for adverse events (CTCAE) version 5.00.
Progression-free survival (PFS)	The evaluation period is up to 24 months from the date of ICF is signed to the date of first recorded progress.	Progression-free survival (PFS) refers to the first treatment of trifluridine/tipiracil to disease progression or death.

Trial Locations

Locations (1)

Chang-Gung Memorial Hospital, Linkou; 🇨🇳 Linkou, Taiwan