Trifluridine/Tipiracil in Combination With Capecitabine and Bevacizumab in Metastatic Colorectal Cancer Patients.

NCT04564898 | Active Not Recruiting Phase 1

• 1 other identifier: 2024-513271-41-00
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 2

Brief Summary

The aim oh this study is to determine the safety and recommended dose of trifluridine/tipiracil plus capecitabine and bevacizumab combination (part 1, dose escalation phase) and to assess its activity in previously untreated mCRC patients who are deemed not eligible for intensive chemotherapy (part 2, expansion phase).

Conditions

Colorectal Cancer Metastatic

Outcome Measures

Primary Outcomes (2)

• recommended dose

  recommended dose of the combination trifluridine/tipiracil plus capecitabine plus bevacizumab

  2 years

• activity

  activity of the combination trifluridine/tipiracil plus capecitabine plus bevacizumab in terms of overaal response rate per RECIST v1.1.

  3 years

Secondary Outcomes (4)

• quality of life for cancer patients

  3 years

• quality of life for colorectal cancer patients

  3 years

• quality of life for dimensions health

  3 years

• survival

  3 years

Other Outcomes (6)

• bioavailability

  2 years

• Steady state concentration

  2 years

• Therapeutic index

  2 years

Study Arms (1)

trifluridine/tipiracil plus capecitabine and bevacizumab

EXPERIMENTAL

Drug: Capecitabine; Drug: Bevacizumab; Drug: Trifluridine/Tipiracil

Interventions

Capecitabine DRUG

Part 1 • Capecitabine, 1000 mg/sqm orally twice daily on days 1-14 each 28 days Part 2 • Capecitabine, 1000 mg/sqm orally twice daily on days 1-14 each 28 days

trifluridine/tipiracil plus capecitabine and bevacizumab

Bevacizumab DRUG

Part 1 • Bevacizumab, 5 mg/kg IV dose over 30 minutes on days 1 and 15 each 28 days Part 2 • Bevacizumab, 5 mg/kg IV dose over 30 minutes on days 1 and 15 each 28 days

trifluridine/tipiracil plus capecitabine and bevacizumab

Trifluridine/Tipiracil DRUG

Part 1 • Trifluridine/tipiracil, dose escalation from 25 mg/sqm to 35 mg/sqm orally twice daily on days 15-19 (and days 22-26) each 28 days Part 2 • Trifluridine/tipiracil, at the recommanded dose established during part 1 orally twice daily on days 15-19 (and days 22-26) each 28 days

trifluridine/tipiracil plus capecitabine and bevacizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent to study procedures.
• Histologically proven diagnosis of colorectal cancer.
• Metastatic colorectal cancer not previously treated with chemotherapy for metastatic disease.
• At least one measurable lesion according to RECIST1.1.
• Age ≥ 18 years.
• ECOG PS ≤ 1.
• Life expectancy of at least 12 weeks.
• Previous adjuvant fluoropyrimidine-based chemotherapy allowed only if more than 12 months elapsed between the end of adjuvant and first relapse.
• Availability of archival tumour tissue (primary tumour and metastases or at least one of the two) for biomarker analysis.
• Availability of blood sample for biomarker analysis.
• Previously not eligible for a chemotherapy doublet or triplet (oxaliplatin and/or irinotecan-based combination).
• Neutrophils ≥1.5 x 109/L, Platelets ≥100 x 109/L, Hemoglobin ≥ 9 g/dl.
• Total bilirubin ≤1.5 fold the upper-normal limits (UNL), AST (SGOT) and/or ALT (SGPT) ≤ 2.5 x UNL (or \<5 x UNL in the case of liver metastases), alkaline phosphatase ≤ 2.5 x UNL (or \<5 x UNL in case of liver metastases).
• Creatinine clearance ≥ 50 mL/min or serum creatinine ≤1.5 x UNL.
• Male subjects with female partners of childbearing potential must be willing to use adequate contraception as approved by the investigator (barrier contraceptive measure or oral contraception).

You may not qualify if:

• Radiotherapy to any site within 4 weeks before the study.
• Previous treatment with trifluridine/tipiracil, bevacizumab and capecitabine (previous treatment with capecitabine was permitted only in the adjuvant setting and if more than 12 months elapsed between the end of adjuvant and first relapse).
• Untreated brain metastases or spinal cord compression or primary brain tumors.
• History or evidence upon physical examination of CNS disease unless adequately treated.
• Clinical signs of malnutrition.
• Active uncontrolled infections or other clinically relevant concomitant illness contraindicating chemotherapy administration.
• Evidence of bleeding diathesis or coagulopathy.
• Uncontrolled hypertension and prior history of hypertensive crisis or hypertensive encephalopathy.
• Clinically significant (i.e. active) cardiovascular disease for example cerebrovascular accidents (≤6 months), myocardial infarction (≤6 months), unstable angina, New York Heart Association (NYHA) grade II or greater congestive heart failure, serious cardiac arrhythmia requiring medication.
• Significant vascular disease (e.g. aortic aneurysm requiring surgical repair or recent arterial thrombosis) within 6 months of study enrolment.
• Any previous venous thromboembolism ≥ NCI CTCAE Grade 4.
• History of abdominal fistula, GI perforation, intra-abdominal abscess or active GI bleeding within 6 months prior to the first study treatment.
• Treatment with any investigational drug within 30 days prior to enrolment or 2 investigational agent half-lives (whichever is longer).
• Other co-existing malignancies or malignancies diagnosed within the last 5 years with the exception of localized basal and squamous cell carcinoma or cervical cancer in situ.
• Lack of physical integrity of the upper gastrointestinal tract, malabsorption syndrome, or inability to take oral medication.

Sponsors & Collaborators

• Gruppo Oncologico del Nord-Ovest: lead

Study Sites (2)

Fondazione IRCCS Istituto Nazionale Tumori

Milan, MI, 20133, Italy

Location

Azienda Ospedaliero Universitaria Pisana

Pisa, PI, 56126, Italy

Location

MeSH Terms

Interventions

Capecitabine; Bevacizumab; trifluridine tipiracil drug combination

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Chiara Cremolini, MD, PhD

  Fondazione GONO

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 12, 2020
• First Posted: September 25, 2020
• Study Start: January 25, 2022
• Primary Completion: May 29, 2024
• Study Completion: March 1, 2026
• Last Updated: January 8, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

IT (2)