BETWEEN: Biweekly Bevacizumab + Trifluridine/Tipiracil to Reduce Grade 3-4 Neutropenia in mCRC Patients

NCT07071844 | Not Yet Recruiting Phase 2

• 1 other identifier: BETWEEN
• Study Type: interventional
• Target: 162
• Locations: 1 country
• Sites: 10

Brief Summary

This study was design to:

• To assess the impact of a biweekly (experimental arm) compared to a conventional administration (control arm) on the rate of grade 3-4 neutropenia in metastatic colorectal cancer (mCRC) patients treated with trifluridine/tipiracil plus bevacizumab, and
• To identify predictive clinical and biological factors for grade 3-4 neutropenia in this patient population.

Conditions

Metastatic Colorectal Cancer

Keywords

Trifluridine/Tipiracil; metastatic colorectal cancer; neutropenia; bevacizumab

Outcome Measures

Primary Outcomes (1)

• The occurrence of at least one grade 3-4 neutropenia

  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).

  From randomization up to 14 days after the end of treatment

Secondary Outcomes (6)

• Overall survival (OS)

  From the date of randomization to the date of death from any cause, assessed up to 3 years

• Progression-free survival (PFS)

  From randomization to the date of the first documented disease progression or death due to any cause, up to 3 years

• Best overall response (BOR)

  From randomization to the date of progression, death or subsequent anti-cancer therapy, up to 3 years

• Disease control rate (DCR)

  Up to achievement of best overall response (BOR) of CR or PR or SD, up to 3 years

• Incidence and grade of adverse events (AEs) and serious adverse events (SAEs) [Safety and tolerability]

  Assessed 28 days after the last administration of treatment or after the end of the treatment visit

Study Arms (2)

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.

Drug: Trifluridine/tipiracil; Drug: Bevacizumab

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.

Drug: Trifluridine/tipiracil; Drug: Bevacizumab

Interventions

Trifluridine/tipiracil DRUG

35 mg/m², orally

Also known as: LONSURF

Arm A (experimental) - Trifluridine/tipiracil plus bevacizumab biweekly administration; Arm B (control) - Trifluridine/tipiracil plus bevacizumab conventional administration

Bevacizumab DRUG

5 mg/kg, intravenous route

Also known as: AVASTIN

Arm A (experimental) - Trifluridine/tipiracil plus bevacizumab biweekly administration; Arm B (control) - Trifluridine/tipiracil plus bevacizumab conventional administration

Eligibility Criteria

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

You may qualify if:

• Signed and dated informed consent,
• Patients willing and able to comply with protocol requirements,
• Age ≥ 18 years,
• ECOG PS 0-1,
• Histologically proven colorectal adenocarcinoma,
• Stage IV disease,
• Previous chemotherapy regimens with each of the following agents: fluoropyrimidine, oxaliplatin, irinotecan, anti-VEGF therapy (bevacizumab, aflibercept, and anti-EGFR therapy (cetuximab or panitumumab for tumors with RAS and/or BRAF wild-type),
• Tumor assessment (CT-scan or MRI) no later than 21 days prior to treatment - at least one measurable or evaluable lesion as assessed by computed tomography (CT)-scan or magnetic resonance imaging (MRI) according to RECIST,
• Known BRAF and RAS mutational status, and microsatellite instability/mismatch repair deficiency (MSI/dMMR) status,
• Have life expectancy of at least 3 months,
• Adequate hematologic function: neutrophils \>1.5 x 10\^9/L; platelets \>100 x 10\^9/L; hemoglobin ≥ 9 g/dL,
• Adequate renal function: Calculated (regardless of the calculation method) creatinine clearance (CrCl) ≥30 mL/min), proteinuria \< 2+ (dipstick urinalysis) or ≤1g / 24h,
• Adequate liver function: aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 x upper limit normal (ULN; ≤5 x ULN in case of liver metastasis), total bilirubin ≤1.5 x ULN (\<2 x ULN if hyperbilirubinemia is due to Gilbert's syndrome), albumin ≥25 g/L,
• Clinical and blood baseline evaluations no later than 14 days prior to treatment,
• Ability to swallow oral tablets,

You may not qualify if:

• ECOG PS 2,
• Local or locally advanced disease (stage I to III),
• Concomitant unplanned antitumor therapy (e.g., chemotherapy, molecular targeted therapy, immunotherapy),
• Unresolved grade ≥3 non-hematologic toxicity related to previous chemotherapy regimen (excluding alopecia and skin pigmentation),
• Treatment with warfarin,
• Symptomatic carcinomatosis with occlusive symptoms or ascites requiring paracentesis,
• Severe or uncontrolled active acute or chronic infection,
• Gastrointestinal disease that could potentially interfere with study drug absorption,
• Uncontrolled diabetes mellitus, hypertension, or cardiac arrhythmia,
• Active (or history of) interstitial lung disease or pulmonary hypertension,
• Severe/unstable angina, or NYHA class III or IV heart failure,
• Systemic immunosuppressive therapy, except steroids given prophylactically or at chronic low dosage (≤20 mg/day prednisone equivalent),
• Radiotherapy within 28 days (4 weeks) before randomization, except for palliation,
• Serious nonhealing wound, ulcer or bone fracture,
• Malignant disease other than mCRC,

Sponsors & Collaborators

• GERCOR - Multidisciplinary Oncology Cooperative Group: lead
• Servier: collaborator

Study Sites (10)

CHU Amiens

Amiens, France

Location

Centre Hospitalier Universitaire -Besançon

Besançon, France

Location

Centre François Baclesse

Caen, France

Location

Centre Hospitalier Departemental Vendee - Site Des Oudairies

La Roche-sur-Yon, France

Location

Centre Hospitaler Universitaire de Lille

Lille, France

Location

Hôpital privé Jean MERMOZ

Lyon, France

Location

CHU Saint-Antoine

Paris, France

Location

Institut Saint Catherine

Paris, France

Location

CHU de BORDEAUX Hôpital HAUT-LEVEQUE

Pessac, France

Location

Institut de cancérologie Strasbourg Europe

Strasbourg, France

Location

MeSH Terms

Conditions

Colorectal Neoplasms; Neutropenia

Interventions

trifluridine tipiracil drug combination; Bevacizumab

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Agranulocytosis; Leukopenia; Cytopenia; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukocyte Disorders

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Jean-Baptiste BACHET, MD

  Pitié-Salpêtrière Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Marie-Line GARCIA LARNICOL, MD

CONTACT

+33 (01) 40 29 85 04; marie-line.garcia-larnicol@gercor.com.fr

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is prospective, multicenter, comparative randomized phase II study design to assess the impact of a biweekly administration (experimental Arm A) compared to a conventional administration (control Arm B) on the rate of grade 3-4 neutropenia in metastatic colorectal cancer (mCRC) patients treated with trifluridine/tipiracil plus bevacizumab.

Study Record Dates

• First Submitted: June 19, 2025
• First Posted: July 17, 2025
• Study Start: September 1, 2025
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2029
• Last Updated: July 17, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

FR (10)