BridgeMD
Safety of Trifluridine/tipiracil in patients with dihydropyrimidine dehydrogenase deficiency diagnosed with metastatic colorectal or gastroesophageal cancer
EU CTIS ID: 2023-508724-35-00
What this study is testing
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.
- 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
- 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)
You likely can't join if
- 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)]
- In case of planned treatment with nivolumab and pembrolizumab: 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 or pembrolizumab : Interstitial lung disease with ongoing signs and symptoms
See the full eligibility criteria
Who can join
- 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
- 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
What rules you out
- 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)]
- In case of planned treatment with nivolumab and pembrolizumab: 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 or pembrolizumab : 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 during the last 30 days before inclusion
- Patients who might be interconnected with or dependent on the sponsor site or the investigator
- Persons deprived of their liberty or under protective custody or guardianship, or legal incapacity or limited legal capacity
- Chronic hepatitis B or C infection (if hepatitis status cannot be obtained from medical records, re-testing is required)
- Patients with CPS≥1 HER2-positive gastroesophageal adenocarcinomas with planned treatment of pembrolizumab if access to pembrolizumab is available.
- Patients with resectable metastases of colorectal cancer.
- Radiotherapy within 28 days prior to first dose of treatment
- Active cardiac disease or abnormal cardiac function including any of the following: a. QT/QTc interval longer than 450 msec for men and longer than 470 msec for women monitored by an ECG at inclusion b. Symptomatic Congestive heart failure ≥New York Heart Association (NYHA) class 3 or 4 c. Severe Unstable angina (angina symptoms at rest) d. Myocardial infarction less than 12 months before first dose of treatment
- Uncontrolled hypertension (Systolic blood pressure ≥140 mmHg or diastolic pressure ≥ 90 mmHg) despite optimal medical management for treatement by bevacizumab
- Ongoing infection ≥Grade 2 (NCI CTCAE v.5.0)
- Known history of human immunodeficiency virus (HIV) infection
- 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
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.