A Study Evaluating S 95005 Plus Bevacizumab and Capecitabine Plus Bevacizumab in Patients With Previously Untreated Colorectal Cancer Who Are Non-eligible for Intensive Therapy

Study Overview
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Brief Summary
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The main purpose of this study is to evaluate the progression-free survival (PFS) in patients receiving S 95005 + bevacizumab (experimental arm) or capecitabine + bevacizumab (control arm) as first-line treatment for unresectable metastatic colorectal cancer in patients non-eligible for intensive therapy.

Official Title
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An Open-label, Randomised, Non-comparative Phase 2 Study Evaluating S 95005 (TAS-102) Plus Bevacizumab and Capecitabine Plus Bevacizumab in Patients With Previously Untreated Metastatic COlorectal Cancer Who Are Non-eligible for Intensive Therapy (TASCO1 Study).

Conditions
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Metastatic Colorectal Cancer

Intervention / Treatment
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* Drug: Trifluridine/tipiracil + bevacizumab
* Drug: Capecitabine + bevacizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent obtained. Has ECOG (Eastern Cooperative Oncology Group) performance status of 0, 1 or 2 at the time of the randomisation. Has definitive histologically or cytologically confirmed adenocarcinoma of the colon or rectum. RAS status must have been determined (mutant or wild). Has at least one measurable metastatic lesion. No previous systemic anticancer therapy for unresectable metastatic colorectal cancer. Previous adjuvant (or neoadjuvant for patients with rectal cancer) chemotherapy is allowed only if if it has been completed more than 6 months before start of study treatment. Patient is not a candidate for combination chemotherapy with irinotecan or oxaliplatin, or for curative resection of metastatic lesions. Is able to take medication orally (i.e., no feeding tube). Has adequate organ function. Coagulation parameters in normal limit (or in therapeutic limit for patients treated with anticoagulant drugs). Women of childbearing potential must have been tested negative in a serum pregnancy test. Female participants of childbearing potential and male participants with partners of childbearing potential must agree to use a highly effective method of birth control. Women and female partners using hormonal contraceptive must also use a barrier method. Exclusion Criteria: Is a pregnant or lactating female. Has certain serious illness or serious medical condition(s) as described in the protocol. Has had certain other recent treatment e.g. major surgery, field radiation, received investigational agent, within the specified time frames prior to randomisation. Has previously received Trifluridine/tipiracil or history of allergic reactions attributed to compounds of similar composition to Trifluridine/tipiracil or any of its excipients. Has rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption. Has contra-indication to bevacizumab or capecitabine.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Trifluridine/tipiracil + bevacizumab<br>Trifluridine/tipiracil (S95005): film-coated tablets containing 15mg of trifluridine and 7.065mg of tipiracil hydrochloride, or 20mg of trifluridine and 9.42mg of tipiracil hydrochloride. Bevacizumab: concentrate for solution for IV infusion containing 25mg/ml of bevacizumab. Trifluridine/tipiracil was administered at 35 mg/m2/dose orally within 1 hour after completion of morning and evening meals, for 5 days on/2 days off, over 2 weeks, followed by a 14-day rest period, with bevacizumab administered intravenously at the dose of 5 mg/kg every 2 weeks at Day 1 and Day 15.This treatment cycle was repeated every 4 weeks. | Drug: Trifluridine/tipiracil + bevacizumab<br>* Patients were treated withTrifluridine/tipiracil + bevacizumab regimen until they met a discontinuation criterion.<br>|
| Active Comparator: Capecitabine + bevacizumab<br>Capecitabine was administered at 1250 mg/m² orally BID (bis in die)on Days 1-14 of each cycle, with bevacizumab (7.5 mg/kg, IV) administered on Day 1 of each cycle. This treatment cycle was repeated every 3 weeks | Drug: Capecitabine + bevacizumab<br>* Patients were treated with capecitabine+ bevacizumab regimen until they met a discontinuation criterion.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival (PFS) | The progression free survival (PFS), defined as the time from the date of randomisation until the date of the investigator-assessed radiological disease progression or death due to any cause according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Progressive disease (PD) was defined at least a 20% increase in the sum of diameters of target lesions (taking as reference the smallest sum on study) and an absolute increase of at least 5 mm in the sum of lesions or the appearance of new lesions. | Baseline and every 8 weeks (maximum follow-up duration: 17.9 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate (ORR) | As per RECIST v1.1, Complete Response (CR) was disappearance of all target lesions; Partial Response (PR) was at least 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. The ORR was the proportion of patients who presented CR or PR with confirmation at subsequent time point or at least 4 weeks later. | Baseline and every 8 weeks (maximum follow-up duration: 17.9 months) | 
| Duration of Response (DR) | The DR was calculated among patients with CR or PR as the time (months) from the first documentation of response to the first documentation of objective tumor progression or death due to any cause, whichever occurred first. | Baseline and every 8 weeks (maximum follow-up duration: 16.6 months) | 
| Disease Control Rate (DCR) | DCR was the proportion of patients with confirmed CR, PR or stable disease (SD) as best overall response. SD defined as neither sufficient decrease to qualify for PR nor sufficient increase to qualify for PD. | Baseline and every 8 weeks (maximum follow-up duration: 17.9 months) | 
| Overall Survival (OS) | The OS was defined as the time from the date of randomisation to the date of death. If death was not confirmed, or patient was alive at study cut-off date, survival time was censored at the date of last follow-up or at the study cut-off date, whichever was earlier. | Baseline up to death or study cut-off (maximum follow-up duration: 19.9 months) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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metastatic, colorectal, cancer, untreated, first-line, S95005 (Trifluridine/tipiracil), bevacizumab, capecitabine