Phase III Study in First-line Treatment of Patients With Metastatic Colorectal Cancer Who Are Not Candidate for Intensive Therapy.

Study Overview
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Brief Summary
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The main purpose of this study is to demonstrate the superiority of S 95005 in combination with bevacizumab over capecitabine in combination with bevacizumab.

Official Title
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An Open-label, Randomised, Phase III Study cOmparing trifLuridine/Tipiracil (S 95005) in Combination With Bevacizumab to Capecitabine in Combination With Bevacizumab in firST-line Treatment of Patients With metastatIC Colorectal Cancer Who Are Not candidatE for Intensive Therapy (SOLSTICE Study)

Conditions
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Metastatic Colorectal Cancer

Intervention / Treatment
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* Drug: Trifluridine/tipiracil hydrochloride (S95005)
* Drug: Capecitabine
* Biological: Bevacizumab experimental
* Biological: Bevacizumab control


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Has definitive histologically confirmed adenocarcinoma of the colon or rectum (all other histological types are excluded). Primary tumour localisation must be known. RAS status based on local biological assessment of tumour biopsy must be available. If RAS status is not available at the time of randomisation, tumour biopsy must be available for RAS status determination (based on local biological assessment). Patient is not a candidate for standard full dose combination chemotherapy with irinotecan or oxaliplatin Patient is not a candidate for curative resection of metastatic lesions. No previous systemic anticancer therapy for unresectable metastatic colorectal cancer. ECOG (Eastern Cooperative Oncology Group) performance status ≤2. Adequate organ function (renal, haematological, hepatic, coagulation) as described in the study protocol' Exclusion Criteria: Pregnancy, breastfeeding or possibility of becoming pregnant during the study. Participation in another interventional study within 4 weeks prior to the randomisation . Patients who have not recovered from clinically relevant non-hematologic CTCAE grade ≥ 3 toxicity of previous anticancer therapy prior to the randomisation. Symptomatic central nervous system metastases. Major surgery within 4 weeks prior to the randomisation. Exclusion criteria related to S 95005 administration: History of allergic reactions attributed to compounds of similar composition to S 95005 or any of its excipients. Any contraindication present in the SmPC of trifluridine/tipiracil Exclusion criteria related to bevacizumab administration: Any contraindication present in the SmPC of bevacizumab Exclusion criteria related to capecitabine administration: Any contraindication present in the SmPC of 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: S95005 + Bevacizumab<br> | Drug: Trifluridine/tipiracil hydrochloride (S95005)<br>* Film-coated tablets of S 95005 (35 mg/m²/dose) will be administered orally twice a day (BID), within 1 hour after completion of morning and evening meals, 5 days on/2 days off, over 2 weeks, followed by a 14-day rest; This treatment cycle will be repeated every 4 weeks.<br>Biological: Bevacizumab experimental<br>* Concentrate for solution for infusion, Bevacizumab (5 mg/kg, IV) administered every 2 weeks (Day 1 and Day 15). This treatment cycle will be repeated every 4 weeks.<br>|
| Active Comparator: Capecitabine + Bevacizumab<br> | Drug: Capecitabine<br>* Film-coated tablets, Capecitabine (1250 mg/m²/dose) will be administered orally BID on Days 1-14 of each cycle. This treatment cycle will be repeated every 3 weeks.<br>Biological: Bevacizumab control<br>* Concentrate for solution for infusion, Bevacizumab (7.5 mg/kg, IV) will be administered on Day 1 of each cycle.This treatment cycle will be repeated every 3 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival (PFS) | Time elapsed between the randomization and the date of radiological tumour progression (according to RECIST 1.1) or death from any cause. | Up to 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) | Time elapsed between the date of randomization and the date of death due to any cause. | Up to 24 months | 
| Overall response rate (ORR) | The proportion of patients with objective evidence of complete response (CR) or partial response (PR) according to RECIST 1.1 criteria and using investigator's tumour assessment. | Up to 24 months | 
| Disease control rate (DCR) | The proportion of patients with objective evidence of CR or PR or stable disease (SD) according to RECIST 1.1 criteria and using investigator's tumour assessment. | Up to 24 months | 
| Duration of response (DoR) | The time from the first documentation of response (CR or PR) to the first documentation of objective tumour progression or death due to any cause, whichever occurs first. | Up to 24 months | 
| Time to treatment failure (TTF) | The time from randomization to treatment discontinuation for any reason, including disease progression, treatment toxicity, patient preference, or death. | Up to 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Metastatic, Cancer, Colorectal, Colorectal Cancer, Colon, Rectum, Metastasis