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

NCT04894123 | Terminated Phase 2

• 1 other identifier: ACOTAS G-098
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 11

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 .

Conditions

Colorectal Adenocarcinoma; Oesogastric

Keywords

cardiac toxicity

Outcome Measures

Primary Outcomes (1)

• Rate of cardiovascular events at 3 months.

  Assessment of the rate of cardiovascular events in patients treated by trifluridine/tipiracil +/- oxaliplatin over a 3-month period.

  At 3 months

Secondary Outcomes (3)

• Number of patients with treatment-related adverse events by CTCAE 5.0

  Assessed up to 48 months

• Number of patients with disease control rate (DCR)

  Assessed up to 48 months

• The 3-month drop-out rate of limiting toxicity

  At 3 months

Study Arms (1)

trifluridine/tipiracil +/- oxaliplatin

EXPERIMENTAL

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.

Drug: Trifluridine/Tipiracil; Drug: Oxaliplatin

Interventions

Trifluridine/Tipiracil DRUG

Trifluridine/tipiracil : 35 mg/m² orally twice a day from day 1 to day 5 every 14 days. If oxaliplatin is stopped or it is not indicated, trifluridine/tipiracil in monotherapy 35 mg/m² orally twice a day between days 1-5 and days 8-12; repeated every 28 days.

Also known as: Lonsurf

trifluridine/tipiracil +/- oxaliplatin

Oxaliplatin DRUG

Oxaliplatin : 85 mg/m² intravenous at day 1 every 14 days.

Also known as: Eloxatin

trifluridine/tipiracil +/- oxaliplatin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed and dated informed consent and willingness to comply with all study procedures and availability for the study duration,
• Histologically confirmed oesogastric, gastric, colon and/or rectum adenocarcinoma
• Patients with metastatic non-resectable (oesogastric or colorectal) or adjuvant (colorectal stage III) adenocarcinoma previously treated by fluoropyrimidines (5-FU or capecitabine),
• Age ≥18 years,
• Eastern Cooperative Oncology Group performance status (ECOG PS) of 0-2,
• Instable angina,
• Acute coronary syndrome (ACS) without ST-segment elevation nor troponin rise.
• Contraindication to continue treatment with 5FU or capecitabine confirmed and documented by a cardiologist,CONFIDENTIAL Protocol ACOTAS version 1.5, 14/06/2021 Page 32 of 93
• Indication to receive trifluridine/tipiracil ± oxaliplatin considered better than absence of therapy (colo-rectal stage III) or the best alternative therapy (metastatic colo-rectal and oeso-gastric or gastric) confirmed by a Multidisciplinary Consultation Meeting
• No contraindication to receive trifluridine/tipiracil (related toxicity),
• No prior treatment with trifluridine/tipiracil,
• Following laboratory values obtained within 14 days (2 weeks) prior to start of study treatment:
• Hematological status: absolute neutrophil count (ANC) ≥ 1.5 x 109/L; platelets ≥ 100 x 109/L; hemoglobin ≥ 9 g/dL,
• Adequate renal function: serum creatinine level \< 150 µM and creatinine clearance ≥ 50 ml/min using the Cockroft-Gault formula,
• Adequate liver function: serum total bilirubin ≤ 1.5 x upper limit of normal (ULN), alkaline phosphatase (ALP) \< 5 x ULN, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN,

You may not qualify if:

• For metastatic colo-rectal-cancer, MSI and/or dMMR tumor
• For metastatic oeso-gastric and gastric adenocarcinoma, HER+++ or HER++ FISH positive tumor
• Left ventricular dysfunction with a left ventricular ejection fraction (LVEF) \< 35% with or without an automatic implantable defibrillator,
• Non-revascularized multivessel coronary artery disease,
• ACS with ST elevation, and/ or troponin rise
• 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.")
• Documented coronary vasospasm during 5-FU treatment leading to myocardial infarction,
• Pregnancy and breastfeeding,
• Treatment with any other investigational medicinal product within 28 days (4 weeks) before start of the study treatment,
• Rare hereditary problems of galactose intolerance, the Lapp lactose deficiency, or glucose-galactose malabsorption,
• Any other serious and uncontrolled non-malignant disease,
• Major surgery or traumatic injury within 28 days (4 weeks) before the start of study treatment,
• Patients with known allergy to any excipient to study drugs,
• Bowel obstruction or inability to swallow tablets,
• Peripheral neuropathy Grade \> 1 for the oxaliplatin schedule,

Sponsors & Collaborators

• GERCOR - Multidisciplinary Oncology Cooperative Group: lead
• Servier: collaborator

Study Sites (11)

CHU Jean Minjoz

Besançon, France

Location

Centre Hospitalier Boulogne/ Mer

Boulogne-sur-Mer, France

Location

Hôptial Henri Mondor

Créteil, France

Location

Chu Dijon

Dijon, France

Location

Hôpital Privé Jean Mermoz

Lyon, France

Location

GH Pitié Salpêtrière

Paris, France

Location

Hôpital Saint Antoine

Paris, France

Location

CHU Poitiers

Poitiers, France

Location

Hôpital Robert Debré

Reims, France

Location

CHU Pontchaillou

Rennes, France

Location

CHU Tours Hôpital Trousseau

Tours, France

Location

MeSH Terms

Conditions

Cardiotoxicity

Interventions

trifluridine tipiracil drug combination; Oxaliplatin

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Drug-Related Side Effects and Adverse Reactions; Chemically-Induced Disorders; Radiation Injuries; Wounds and Injuries

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 16, 2021
• First Posted: May 20, 2021
• Study Start: February 7, 2022
• Primary Completion: February 13, 2023
• Study Completion: February 13, 2023
• Last Updated: September 18, 2023

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will not share

Locations

FR (11)