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BEvacizumab plus Trifluridine/tipiracil in a bi-WEEkly administration to reduce grade 3-4 Neutropenia in patients with mCRC: A prospective, multicenter, comparative, randomized GERCOR G-124 BETWEEN phase II study.
EU CTIS ID: 2024-520128-27-00
What this study is testing
Assess the occurrence of grade 3-4 neutropenia (adverse drug reaction) 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).
- Therapeutic exploratory (Phase II)
A plain-language read of the study's public EU CTIS listing. The study team confirms the details.
Who can take part
You may be able to join if
- Signed and dated informed consent,
- Life expectancy of at least 3 months,
- Adequate hematologic function: neutrophils >1.5 x 109/L; platelets >100 x 109/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; ≤5x ULN in case of liver metastasis), total bilirubin ≤1.5 x ULN (<2x 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 inclusion,
You likely can't join if
- ECOG PS 2,
- Other serious and uncontrolled non-malignant disease (e.g., active infection requiring systemic therapy, coronary stenting or myocardial infarction, or stroke in the past 6 months prior to inclusion),
- Severe or uncontrolled active acute or chronic infection,
- Major surgery within 28 days (4 weeks) prior to inclusion,
- Gastrointestinal disease that could potentially interfere with study drug absorption,
- Uncontrolled diabetes mellitus, hypertension, or cardiac arrhythmia,
See the full eligibility criteria
Who can join
- Signed and dated informed consent,
- Life expectancy of at least 3 months,
- Adequate hematologic function: neutrophils >1.5 x 109/L; platelets >100 x 109/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; ≤5x ULN in case of liver metastasis), total bilirubin ≤1.5 x ULN (<2x 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 inclusion,
- Ability to swallow oral tablets,
- Women must be surgically sterile or postmenopausal, or not be pregnant, breastfeeding, or expecting to conceive during the study. Women of childbearing potential (WOCBP) must have a negative serum pregnancy test within 72 hours (3 days) prior to starting trifluridine/tipiracil treatment. WOCBP must agree to use an adequate method of contraception or birth control for the duration of study treatment and least 6 months (trifluridine/tipiracil, bevacizumab) after the last dose of the study treatment,
- Males who are fertile and sexually active with WOCBP must agree to follow instructions for method(s) of contraception for the duration of study treatment and at least 6 months (trifluridine/tipiracil, bevacizumab) after the last dose of the study treatment.
- Is willing and able to comply with scheduled visits, treatment schedule, laboratory tests, tumor biopsies, and other requirements of the study,
- Registration with the French National Health Care System or PUMA (Protection Universelle Maladie).
- 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 (computed tomography [CT]-scan or magnetic resonance imaging [MRI]) no later than 21 days prior to inclusion - at least one measurable or evaluable lesion as assessed by CT-scan or MRI according to RECIST v1.1,
- Known BRAF and RAS mutational status, and microsatellite instability/mismatch repair deficiency (MSI/dMMR) status,
What rules you out
- ECOG PS 2,
- Other serious and uncontrolled non-malignant disease (e.g., active infection requiring systemic therapy, coronary stenting or myocardial infarction, or stroke in the past 6 months prior to inclusion),
- Severe or uncontrolled active acute or chronic infection,
- Major surgery within 28 days (4 weeks) prior to inclusion,
- 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,
- Major adverse cardiovascular event within 6 months before randomization,
- 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) prior to inclusion, except for palliation,
- Medical history or evidence of CNS metastasis upon physical examination, unless adequately treated (e.g., non-irradiated CNS metastasis, seizure not controlled with standard medical therapy, patients are stable without evidence of progression for at least 28 days prior to inclusion),
- Serious nonhealing wound, ulcer or bone fracture,
- Deep vein thromboembolic event within 28 days (4 weeks) prior to inclusion,
- Known clinically relevant coagulopathy, bleeding diathesis or bleeding event within 28 days (4 weeks) prior to inclusion,
- Malignant disease other than mCRC,
- Other concomitant or previous malignancy, except i/ adequately treated in-situ carcinoma of the uterine cervix, ii/ basal or squamous cell carcinoma of the skin, iii/ cancer in complete remission for >5 years,
- Rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption. NB: In patients who have previously received or are receiving intravenous bisphosphonates, invasive dental procedures should be avoided, if possible. NB: Caution is required when using medicinal products that are human thymidine kinase substrates, e.g., zidovudine. Such medicinal products, if used concomitantly with trifluridine/tipiracil, may compete with the effector, trifluridine, for activation via thymidine kinases. Therefore, when using antiviral medicinal products that are human thymidine kinase substrates, monitor for possible decreased efficacy of the antiviral medicinal product, and consider switching to an alternative antiviral medicinal product that is not a human thymidine kinase substrate, such as lamivudine, didanosine, and abacavir. NB: It is unknown whether trifluridine/tipiracil may reduce the effectiveness of hormonal contraceptives. Therefore, women using hormonal contraceptive must also use a barrier contraceptive method.
- Human immunodeficiency virus (HIV)-infected patients or otherwise known to be HIV-positive,
- Untreated hepatitis B virus (HBV) or hepatitis C virus (HCV),
- Concomitant administration of prophylactic phenytoin and live attenuated virus vaccine such as yellow fever vaccine 28 days (4 weeks) prior to treatment,
- Impossibility of submitting to the medical follow-up of the study for geographical, social, or psychiatric illness,
- Local or locally advanced disease (stage I to III),
- Under legal protection regime (guardianship, curatorship, judicial safeguard) or administrative decision or incapability of giving consent.
- Concomitant unplanned antitumor therapy (e.g., chemotherapy, molecular targeted therapy, immunotherapy),
- Unresolved grade ≥3 nonhematologic toxicity related to previous chemotherapy regimen (excluding alopecia and skin pigmentation)
- Dihydropyrimidine dehydrogenase (DPD) deficiency (uracilemia dosage >16 ng/ml); Uracilemia dosing results must be available before inclusion,
- Treatment with warfarin,
- Treatment with any other IMP within 28 days prior to inclusion,
- Symptomatic carcinomatosis with occlusive symptoms or ascites requiring paracentesis,
The study team makes the final eligibility decision.
Questions & answers
Do participants get paid in this trial?
This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.
Is it free to join, and do I need insurance?
Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.
How long does this study last?
The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.
Who can join this trial?
This study is enrolling all sexes, 18-64 years, 65+ years. The study team makes the final eligibility decision.
Explore other conditions
BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from EU CTIS; the study team decides eligibility.