TRIFLUOX-DP: Safety of Trifluridine/tipiracil as replacement of fluoropyrimidines (5-fluorouracil and capecitabine) based chemotherapy as first line metastatic colorectal or gastroesophageal cancer regimens in patients with dihydropyrimidine dehydrogenase deficiency: a phase II trial

Unicancer21 sites in 1 country73 target enrollmentMarch 21, 2025

DrugsTRASTUZUMAB Lonsurf 20 mg/8.19 mg film-coated tablets, Lonsurf 15 mg/6.14 mg film-coated tablets NIVOLUMAB Lonsurf 20 mg/8.19 mg film-coated tablets TRIFLUOROTHYMIDINE Lonsurf 15 mg/6.14 mg film-coated tablets BEVACIZUMAB PANITUMUMAB OXALIPLATIN

Overview

Phase: Phase 2
Intervention: Not specified
Conditions: Not specified
Sponsor: Unicancer
Enrollment: 73
Locations: 21
Primary Endpoint: The co-primary endpoint including: the rate of patients without specific toxicities defined as grade 3-4-5 digestive toxicities (diarrhoea and/or stomatitis) and grade 4-5 neutropenia or febrile neutropenia over the first 2 cycles (1 month of treatment) of first-line metastatic treatment (NCI CTCAE v5.0) AND the disease control rate after the 1st evaluation at 2 months of treatment.
Status: Recruiting
Last Updated: 4 months ago

Overview Investigators Eligibility Criteria Outcomes Sites Similar Trials

Overview

Brief Summary

To evaluate the specific safety and preliminary efficacy of an alternative chemotherapy option, namely Trifluridine/tipiracil, as replacement of 5FU- or capecitabine-based chemotherapy in pMMR/MSS metastatic colorectal or metastatic gastroesophageal adenocarcinomas first line regimens for patients with partial or complete DPD deficiency.

Registry

euclinicaltrials.eu

Start Date

March 21, 2025

End Date

October 21, 2028

Last Updated

4 months ago

Study Type

Interventional

Study Design

Parallel

Investigators

Sponsor

Unicancer

Responsible Party

Principal Investigator

Nourredine AIT RAHMOUNE

Scientific

Unicancer

Eligibility Criteria

Inclusion Criteria

•Patient must have signed and dated a written informed consent form prior to any trial specific procedures. When the patient is physically unable to give their written consent, a trusted person of their choice, independent from the investigator or the sponsor, can confirm in writing the patient’s consent.
•For women of reproductive potential, negative serum beta human chorionic gonadotropin (β- HCG) pregnancy test obtained within 7 days before the start of study treatment. Women not of reproductive potential are female patients who are postmenopausal or permanently sterilized (e.g., tubal occlusion, hysterectomy, bilateral salpingectomy)
•For women of childbearing potential and men, agreement to use an adequate contraception for the duration of study participation and up to 7 months following completion of therapy
•Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests and other study procedures
•Affiliation to the Social Security System (or equivalent).
•Histological or cytological documentation of proficient mismatch repair or microsatellite stable (pMMR/MSS) adenocarcinoma of the colon or rectum OR gastroesophageal cancer (lower oesophagus, gastroesophageal junction and gastric)
•Unresectable synchronous or metachronous metastatic colorectal or gastroesophageal cancer
•Presence of at least one measurable lesion according to RECIST v1.1
•No prior therapy for metastatic disease
•Known DPD deficiency defined as plasma uracil concentration≥16 ng/ml

Exclusion Criteria

•Previous or concurrent cancer that is distinct in primary site or histology from colorectal or gastroesophageal cancer within 5 years prior to study inclusion, except for curatively treated cervical cancer in situ, non-melanoma skin cancer and superficial bladder tumours [Ta (non invasive tumour), Tis (carcinoma in situ) and T1 (lamina propria invasion)]
•Chronic hepatitis B or C infection (if hepatitis status cannot be obtained from medical records, re-testing is required)
•Seizure disorder requiring medication
•Symptomatic metastatic brain or meningeal tumours
•History of organ allograft
•Known hypersensitivity to any of the study drugs, study drug classes, or any constituent of the products
•Use of live or live attenuated vaccines
•Ongoing toxicities: a. Peripheral neuropathy >Grade 1 (NCI CTCAE v.5.0) b. Unresolved Grade 3 or 4 non-haematological clinically relevant toxicity from prior therapies
•Hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption or any uncontrolled malabsorption condition
•Inability to swallow oral medication

Outcomes

Primary Outcomes

The co-primary endpoint including: the rate of patients without specific toxicities defined as grade 3-4-5 digestive toxicities (diarrhoea and/or stomatitis) and grade 4-5 neutropenia or febrile neutropenia over the first 2 cycles (1 month of treatment) of first-line metastatic treatment (NCI CTCAE v5.0) AND the disease control rate after the 1st evaluation at 2 months of treatment.

Secondary Outcomes

Safety of combination treatment (NCI CTCAE v5.0) determined through the incidence of adverse events, treatment-related adverse events, serious adverse events (SAE), and death; for the whole population and depending on glomerular filtration rate ([50-60[ vs [60- 90[ vs ≥90 mL/min per 1.73 m2)
Dose intensity of combination treatment per patient and per cycle for cycle 1 and cycle 2 before third cycle
Treatment efficacy : PFS, Overall survival, Objective response rate, Disease control rate
Health-related quality of life will be assessed using the EORTC QLQ-C30 and EORTC QLQ-OG25 questionnaires for patients with gastroesophageal adenocarcinomas or EORTC QLQ-CR29 for patients with colorectal adenocarcinomas at baseline and every 2 months until disease progression and/or at least 3 months after study treatment stop