Approval Probability 71%
TA Base Rate26%
Adjusted LOA41%
ML RiskLOW_RISK
| NCT ID | Title | Phase | Status | Enrollment | Velocity | Design | Start | Completion | Last Updated | Sites | Countries |
|---|---|---|---|---|---|---|---|---|---|---|---|
| NCT03869892 | Phase III Study in First-line Treatment of Patients With Metastatic Colorectal Cancer Who Are Not Candidate for Intensive Therapy. | PHASE3 | ACTIVE NOT_RECRUITING | 856 | — | — | Mar 21, 2019 | Dec 31, 2026 | Dec 22, 2025 | 190 | Argentina, Australia +23 |
| NCT03306394 | A Study of Trifluridine/Tipiracil (Also Known as S 95005 or TAS-102) in Patients With a Pretreated Colorectal Cancer That Has Spread (Metastatic). | PHASE3 | COMPLETED | 907 | — | — | Oct 18, 2016 | Nov 30, 2020 | Jul 25, 2024 | 99 | Australia, Belgium +14 |
| NCT07071844 | BETWEEN: Biweekly Bevacizumab + Trifluridine/Tipiracil to Reduce Grade 3-4 Neutropenia in mCRC Patients | PHASE2 | NOT YET_RECRUITING | 162 | — | — | Sep 1, 2025 | Dec 1, 2029 | Jul 17, 2025 | 10 | France |
| NCT02743221 | 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 | PHASE2 | COMPLETED | 154 | — | — | Apr 29, 2016 | Sep 1, 2020 | Aug 20, 2024 | 57 | Australia, Belgium +10 |
| NCT02848443 | Study of S 95005 in Combination With Oxaliplatin in Metastatic Colorectal Cancer | PHASE1 | COMPLETED | 78 | — | — | May 1, 2016 | Apr 9, 2020 | Jul 25, 2024 | 24 | Austria, France +5 |
Time elapsed between the randomization and the date of radiological tumour progression (according to RECIST 1.1) or death from any cause.
The occurrence of 3-4 neutropenia in mCRC patients undergoing treatment with the combination of bevacizumab and bi-weekly administration of trifluridine/tipiracil (experimental arm) compared to a conventional administration (control arm).
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.
Adverse event reporting will be graded following the National Cancer Institute of Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03
Vital sign measurements will include temperature, systolic and diastolic blood pressure, heart rate, and respiratory rate.
| Arm | Type | Description |
|---|---|---|
| S95005 + Bevacizumab | EXPERIMENTAL | - |
| Capecitabine + Bevacizumab | ACTIVE_COMPARATOR | - |
| S95005 | EXPERIMENTAL | Film-coated tablet containing 15 mg of trifluridine and 7.065 mg of tipiracil hydrochloride, or 20 mg of trifluridine and 9.42 mg of tipiracil hydrochloride, taken orally twice a day at the dose of 35 mg/m²/dose. The treatment is given until progression of disease, unacceptable toxicity, investigator decision, patient refusal or until market authorization or reimbursement has been granted by the relevant Authority of the country where that patient is treated or until trifluridine / tipiracil is available by a doctor's prescription or can be accessed from another source or Sponsor decision. |
| Arm A (experimental) - Trifluridine/tipiracil plus bevacizumab biweekly administration | EXPERIMENTAL | Trifluridine/tipiracil: 35 mg/m², twice daily (BId) orally, on days 1-5 and days 15-19; 1 cycle every 28 days. \+ Bevacizumab: 5 mg/kg intravenously (IV) on day 1 and day 15; 1 cycle every 28 days. |
| Arm B (control) - Trifluridine/tipiracil plus bevacizumab conventional administration | ACTIVE_COMPARATOR | Trifluridine/tipiracil: 35 mg/m² Bid orally on days 1-5 and days 8-12; 1 cycle every 28 days. \+ Bevacizumab: 5 mg/kg IV on day 1 and day 15; 1 cycle every 28 days. |
| Trifluridine/tipiracil + bevacizumab | EXPERIMENTAL | 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. |
| S 95005 + oxaliplatin (+/- bevacizumab or nivolumab) | EXPERIMENTAL | - |
| Name | Type | Description |
|---|---|---|
| Trifluridine/tipiracil hydrochloride (S95005) | DRUG | 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. |
| Capecitabine | DRUG | 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. |
| Bevacizumab experimental | BIOLOGICAL | 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. |
| Bevacizumab control | BIOLOGICAL | 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. |
| Trifluridine/tipiracil | DRUG | 35 mg/m², orally |
| Bevacizumab | DRUG | 5 mg/kg, intravenous route |
| Trifluridine/tipiracil + bevacizumab | DRUG | Patients were treated withTrifluridine/tipiracil + bevacizumab regimen until they met a discontinuation criterion. |
| Capecitabine + bevacizumab | DRUG | Patients were treated with capecitabine+ bevacizumab regimen until they met a discontinuation criterion. |
| Trifluridine/tipiracil hydrochloride (S 95005) | DRUG | Film-coated tablets containing 15mg of trifluridine and 7.065mg of tipiracil hydrochloride, or 20mg of trifluridine and 9.42mg of tipiracil hydrochloride, given orally at the dose of 25 or 30 or 35 mg/m2/dose, until unacceptable toxicity according to the investigator, disease progression or patient withdrawal. |
| Oxaliplatin | DRUG | Concentrate for solution for infusion containing 5mg/ml of oxaliplatin, administered intravenously at the dose of 65 to 85 mg/m2, until unacceptable toxicity according to the investigator, disease progression or patient withdrawal. |
| Nivolumab | DRUG | Concentrate for solution for infusion containing 10mg/ml of nivolumab, administered intravenously at the dose of 3 mg/kg, until unacceptable toxicity according to the investigator, disease progression or patient withdrawal. |
Inclusion Criteria: 1. Has definitive histologically confirmed adenocarcinoma of the colon or rectum (all other histological types are excluded). Primary tumour localisation must be known. 2. RAS status based on local biological assessment of tumour biopsy must be available. If RAS status is not av...