Safety of Trifluridine/tipiracil in patients with dihydropyrimidine dehydrogenase deficiency diagnosed with metastatic colorectal or gastroesophageal cancer

Phase 1

• Conditions: Patients with pMMR/MSS metastatic adenocarcinoma of the colon or rectum or gastroesophageal cancer (lower esophagus, gastroesophageal junction and gastric) and with known dihydropyrimidine dehydrogenase (DPD) deficiency defined as plasma uracil concentration =16 ng/ml, who undergo first-line treatment; Therapeutic area: Diseases [C] - Neoplasms [C04]

• Registration Number: CTIS2023-508724-35-00
• Lead Sponsor: nicancer

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2024-04-26
• Last Update Posted: 21 August 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 73

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 (ß- 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, Age =18 years, Eastern Cooperative Oncology Group (ECOG) performance status =1, Adequate bone marrow, renal, and liver functions as evidenced by the laboratory requirements within 7 days prior to study treatment initiation

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, In case of planned treatment with nivolumab: a. Participant has received systemic steroid therapy (>10 mg daily prednisone or equivalent) or is receiving any other form of immunosuppressive medication. b. Active autoimmune disease or medical conditions requiring systemic immunosuppression that has required systemic treatment, Patients with colorectal cancer with high microsatellite instability (MSI-H) or mismatched repair disease (dMMR) tumor, In case of planned treatment with trastuzumab: a. a threshold value for the left ventricular ejection fraction (LVEF) measured at inclusion that does not allow treatment with trastuzumab (<55%), b. severe dyspnoea at rest due to complications of advanced malignancy or requiring supplementary oxygen therapy c. Known hypersensitivty to murine proteins, In case of planned treatment with bevacizumab: a. Proteinuria that does not allow treatment with bevacizumab, b. Pre-existing gastrointestinal or non-gastrointestinal fistula, c. Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to first dose of treatment d. Evidence or history of any bleeding diathesis, irrespective of severity. Any hemorrhage or bleeding event =CTCAE v 5.0 Grade 3 within 4 weeks prior to the start of study medication e. Prior arterial thromboembolic reactions, including cerebrovascular accidents, transient ischaemic attacks less than 12 months before first dose of bevacizumab f. Known hypersensitivity to Chinese Hamster Ovary (CHO) cell products or other recombinant human or humanized antibodies, In case of planned treatment with trastuzumab or panitumumab or bevacizumab: Interstitial lung disease with ongoing signs and symptoms, Pregnant or breast-feeding subjects. Women of childbearing potential must have a serum pregnancy test performed a maximum of 7 days before start of treatment, and a negative result must be documented before start of study drug, Patients unwilling or unable to comply with the medical follow-up required by the trial because of geographic, familial, social, substance abuse, medical or psychological reasons, or any condition that, in the opinion of the investigator, would interfere with the patient’s participation in the study or evaluation of study treatment or interpretation of patient safety or study results, Participation in another clinical study with an investigational product durin

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified