Cardiovascular Events From Trifluridine/Tipiracil +/- Oxaliplatin in Colorectal/Oesogastric Adenocarcinoma Patients

Phase 2

Terminated

• Conditions: Colorectal Adenocarcinoma; Oesogastric
• Interventions: Drug: Trifluridine/Tipiracil; Drug: Oxaliplatin

• Registration Number: NCT04894123
• Lead Sponsor: GERCOR - Multidisciplinary Oncology Cooperative Group

Brief Summary

The purpose of this study is to assess the incidence of cardiovascular events in patients with esophageal/stomach or colorectal cancer treated by trifluridine/tipiracil +/- oxaliplatin after an episode of cardiac angina-related thoracic pain due to fluoropyrimidines in the adjuvant or metastatic setting .

Detailed Description

After being informed about the study and potential risks, all patients giving written informed consent will undergo a 14-day screening period to determine eligibility for study entry. Patient who meet the eligibility requirement will be included in the study and will be treated by trifluridine/tipiracil +/- oxaliplatin.

Study Timeline

• Study First Submitted: 2021-05-16
• Study First Submitted QC: 2021-05-16
• Study First Posted: 2021-05-20
• Study Start: 2022-02-07
• Primary Completion: 2023-02-13
• Study Completion: 2023-02-13
• Status Verified: 2023-09
• Last Update Submitted: 2023-09-14
• Last Update Posted: 2023-09-18

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 1

Inclusion Criteria

Not provided

Exclusion Criteria

1. For metastatic colo-rectal-cancer, MSI and/or dMMR tumor

2. For metastatic oeso-gastric and gastric adenocarcinoma, HER+++ or HER++ FISH positive tumor

3. Left ventricular dysfunction with a left ventricular ejection fraction (LVEF) < 35% with or without an automatic implantable defibrillator,

4. Non-revascularized multivessel coronary artery disease,

5. ACS with ST elevation, and/ or troponin rise

6. QT/QTc interval > 470 ms (for women) and > 450 ms (for men) NB: Caution is required when using medicinal products with human thymidine kinase substrates, e.g. zidovudine and other drugs known to prolong the QTc interval (exhaustive list on https: //www.crediblemeds.org.")

7. Documented coronary vasospasm during 5-FU treatment leading to myocardial infarction,

8. Pregnancy and breastfeeding,

9. Treatment with any other investigational medicinal product within 28 days (4 weeks) before start of the study treatment,

10. Rare hereditary problems of galactose intolerance, the Lapp lactose deficiency, or glucose-galactose malabsorption,

11. Any other serious and uncontrolled non-malignant disease,

12. Major surgery or traumatic injury within 28 days (4 weeks) before the start of study treatment,

13. Patients with known allergy to any excipient to study drugs,

14. Bowel obstruction or inability to swallow tablets,

15. Peripheral neuropathy Grade > 1 for the oxaliplatin schedule,

16. Non resolved non-hematological toxicities from prior therapies (grade >2),

17. Abnormal values at inclusion for :

    • kalemia ;
    • Magnesemia;
    • Calcemia and corrected calcium level

18. Patient under a legal protection regime (guardianship, curatorship, judicial safeguard), or administrative decision, or incapable of giving his/her consent

19. Impossibility of submitting to the medical follow-up of the study for geographical, social reasons or psychiatric illness.

20. Patients admitted to a health or social establishment for purposes other than that of the study

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
trifluridine/tipiracil +/- oxaliplatin	Trifluridine/Tipiracil	Trifluridine/tipiracil 35 mg/m² orally twice a day from day 1 to day 5 plus oxaliplatin 85 mg/m² intravenous at day 1 every 14 days. If oxaliplatin is stopped for neurotoxicity, allergic reaction or other reason, or it is not indicated, patients will continue trifluridine/tipiracil in monotherapy 35 mg/m² orally twice a day between days 1-5 and days 8-12; repeated every 28 days.
trifluridine/tipiracil +/- oxaliplatin	Oxaliplatin	Trifluridine/tipiracil 35 mg/m² orally twice a day from day 1 to day 5 plus oxaliplatin 85 mg/m² intravenous at day 1 every 14 days. If oxaliplatin is stopped for neurotoxicity, allergic reaction or other reason, or it is not indicated, patients will continue trifluridine/tipiracil in monotherapy 35 mg/m² orally twice a day between days 1-5 and days 8-12; repeated every 28 days.

Primary Outcome Measures

Name	Time	Method
Rate of cardiovascular events at 3 months.	At 3 months	Assessment of the rate of cardiovascular events in patients treated by trifluridine/tipiracil +/- oxaliplatin over a 3-month period.

Secondary Outcome Measures

Name	Time	Method
Number of patients with treatment-related adverse events by CTCAE 5.0	Assessed up to 48 months	Safety profile of the trifluridine/tipiracil and oxaliplatin combination
The 3-month drop-out rate of limiting toxicity	At 3 months	Drop-out rate defined as the number of patients who left the study due to limiting toxicity between treatment initiation and 3 months.
Number of patients with disease control rate (DCR)	Assessed up to 48 months	DCR defined as partial response, complete response (CR), or stable disease (SD).

Trial Locations

Locations (11)

Centre Hospitalier Boulogne/ Mer; 🇫🇷 Boulogne-sur-Mer, France

Hôpital Saint Antoine; 🇫🇷 Paris, France

CHU Jean Minjoz; 🇫🇷 Besançon, France

Hôptial Henri Mondor; 🇫🇷 Créteil, France

Hôpital Privé Jean Mermoz; 🇫🇷 Lyon, France

Chu Dijon; 🇫🇷 Dijon, France

GH Pitié Salpêtrière; 🇫🇷 Paris, France

CHU Poitiers; 🇫🇷 Poitiers, France

Hôpital Robert Debré; 🇫🇷 Reims, France

CHU Tours Hôpital Trousseau; 🇫🇷 Tours, France

CHU Pontchaillou; 🇫🇷 Rennes, France