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.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Association Gercor

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Digestive System Diseases [C06]

Trial duration

4 Mar 2026 → ongoing

Decision date (initial)

2025-10-20

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Safety

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).

Secondary objectives 9

1. Evaluate OS in both arms,
2. Evaluate PFS in both arms,
3. Evaluate objective response rate (ORR) according to Response Evaluation Criteria Solid Tumors (RECIST) v1.1 in both arms,
4. Evaluate disease control rate (DCR) in both arms according to RECIST v1.1,
5. Evaluate OS, PFS, ORR and DCR in the subgroups of patients with at least one episode of grade 3-4 neutropenia or without grade 3-4 neutropenia in both arms,
6. Evaluate safety and tolerance in both arms according to NCI-CTCAE v 5.0,
7. Evaluate treatment administration (dose delay, dose reduction, dose reduction not related to grade 3-4 neutropenia) in both arms,
8. Evaluate treatment compliance in the all-treated patients in both arms,
9. Assess Eastern Cooperative Oncology Group performance status (ECOG PS) in both arms,

Conditions and MedDRA coding

colorectal adenocarcinoma

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 19

1. Signed and dated informed consent,
2. Patients willing and able to comply with protocol requirements,
3. Age ≥ 18 years,
4. ECOG PS 0-1,
5. Histologically proven colorectal adenocarcinoma,
6. Stage IV disease,
7. 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),
8. 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,
9. Known BRAF and RAS mutational status, and microsatellite instability/mismatch repair deficiency (MSI/dMMR) status,
10. Life expectancy of at least 3 months,
11. Adequate hematologic function: neutrophils >1.5 x 109/L; platelets >100 x 109/L; hemoglobin ≥ 9 g/dL,
12. Adequate renal function: Calculated (regardless of the calculation method) creatinine clearance (CrCl) ≥30 mL/min, proteinuria <2+ (dipstick urinalysis) or ≤1g / 24h,
13. 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,
14. Clinical and blood baseline evaluations no later than 14 days prior to inclusion,
15. Ability to swallow oral tablets,
16. 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,
17. 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.
18. Is willing and able to comply with scheduled visits, treatment schedule, laboratory tests, tumor biopsies, and other requirements of the study,
19. Registration with the French National Health Care System or PUMA (Protection Universelle Maladie).

Exclusion criteria 30

1. ECOG PS 2,
2. 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),
3. Local or locally advanced disease (stage I to III),
4. Concomitant unplanned antitumor therapy (e.g., chemotherapy, molecular targeted therapy, immunotherapy),
5. Unresolved grade ≥3 nonhematologic toxicity related to previous chemotherapy regimen (excluding alopecia and skin pigmentation)
6. Dihydropyrimidine dehydrogenase (DPD) deficiency (uracilemia dosage >16 ng/ml); Uracilemia dosing results must be available before inclusion,
7. Treatment with warfarin,
8. Treatment with any other IMP within 28 days prior to inclusion,
9. Symptomatic carcinomatosis with occlusive symptoms or ascites requiring paracentesis,
10. 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),
11. Severe or uncontrolled active acute or chronic infection,
12. Major surgery within 28 days (4 weeks) prior to inclusion,
13. Gastrointestinal disease that could potentially interfere with study drug absorption,
14. Uncontrolled diabetes mellitus, hypertension, or cardiac arrhythmia,
15. Active (or history of) interstitial lung disease or pulmonary hypertension,
16. Major adverse cardiovascular event within 6 months before randomization,
17. Severe/unstable angina, or NYHA class III or IV heart failure,
18. Systemic immunosuppressive therapy, except steroids given prophylactically or at chronic low dosage (≤20 mg/day prednisone equivalent),
19. Radiotherapy within 28 days (4 weeks) prior to inclusion, except for palliation,
20. Serious nonhealing wound, ulcer or bone fracture,
21. Deep vein thromboembolic event within 28 days (4 weeks) prior to inclusion,
22. Known clinically relevant coagulopathy, bleeding diathesis or bleeding event within 28 days (4 weeks) prior to inclusion,
23. Malignant disease other than mCRC,
24. 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,
25. 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.
26. Human immunodeficiency virus (HIV)-infected patients or otherwise known to be HIV-positive,
27. Untreated hepatitis B virus (HBV) or hepatitis C virus (HCV),
28. Concomitant administration of prophylactic phenytoin and live attenuated virus vaccine such as yellow fever vaccine 28 days (4 weeks) prior to treatment,
29. Impossibility of submitting to the medical follow-up of the study for geographical, social, or psychiatric illness,
30. Under legal protection regime (guardianship, curatorship, judicial safeguard) or administrative decision or incapability of giving consent.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The occurrence of grade 3-4 neutropenia in patients undergoing treatment with the combination of bevacizumab and bi-weekly administration of trifluridine/tipiracil (experimental arm) compared to a conventional administration (control arm).

Secondary endpoints 9

1. OS in both arms,
2. PFS in both arms,
3. BOR in both arms,
4. DCR in both arms,
5. OS, PFS, BOR, and DCR in subgroups of patients with at least one episode of grade 3-4 neutropenia or without grade 3-4 neutropenia in both arms,
6. Incidence and grade of AEs and SAEs in both arms,
7. Incidence of dose delay, dose reduction, and dose reduction not related to grade 3-4 neutropenia in both arms,
8. Treatment compliance (Percentage of patients with compliance to treatment) in both arms,
9. Time to ECOG PS deterioration.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Association Gercor

Sponsor organisation

Association Gercor

Address

151 Rue Du Faubourg Saint Antoine

City

Paris

Postcode

75011

Country

France

Scientific contact point

Organisation

Association Gercor

Contact name

Marie Line Garcia Larnicol

Public contact point

Organisation

Association Gercor

Contact name

Marie Line Garcia Larnicol

Locations

1 EU/EEA country · 23 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 18 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications