HERES trial: Trastuzumab and standard treatment with chemo- and immunotherapy as first line treatment for HER2 positive esophageal squamous cell carcinoma patients

Phase 2

Recruiting

• Conditions: Esophageal Cancer

• Registration Number: 2024-516318-40-02
• Lead Sponsor: Rigshospitalet, Frederiksberg Hospital

Brief Summary

To determine the efficacy of trastuzumab added to standard treatment (fluoropyrimidine/platinum doublet with pembrolizumab) in patients with ESCC determined by 6 months progression free survival (PFS) (RECIST 1.1).

Detailed Description

Not available

Study Timeline

• Study First Posted: 2024-11-29
• Last Update Posted: 2025-01-14

Recruitment & Eligibility

• Status: Ongoing, recruiting
• Sex: Not specified
• Target Recruitment: 24

Inclusion Criteria

1. Signed informed consent

2. Age ≥18 years

Inoperable locally advanced or metastatic squamous cell carcinoma of the esophagus not amenable for curative intended therapy

HER2 positive defined as either: a. IHC1+ and ISH positive (amplification ratio (HER2/CEP17) ≥ 2.0) and a high gene count fulfilling either: (HER2/cell) ≥ 6.0 or (HER2/cell) ≥ 4.0 assessed by two different ISH probes b. IHC2+ and ISH positive (ISH amplification ratio (HER2/CEP17) ≥ 2.0) c. IHC3+

ECOG PS <2

Baseline left ventricular ejection fraction > 50% measured by echocardiography or MUGA

Adequate bone marrow function and organ function: a. Leucocytes > 3.0 x 109/l, neutrocytes > 1.5 x 109/l and thrombocytes > 100 x 109/l b. Serum bilirubin < 1.5 × upper limit of normal (ULN); and AST/ALT < 2.5 × ULN (or < 5 × ULN in patients with liver metastases). c. Creatinine clearance > 30 ml/min

Exclusion Criteria

Prior systemic treatment with non-curative intent including HER2-targeting drugs. Prior neoadjuvant and adjuvant therapies as well as palliative radiotherapy are allowed

Allopurinol, phenytoin, warfarin treatment is not allowed. Non vitamin K oral anticoagulants (NOAK) and low molecular weight (LMW) heparin is allowed

Pregnancy or breast-feeding

Positive serum pregnancy test in women of childbearing potential

Subjects with reproductive potential not willing to use an effective method of contraception under and 3 months after participation in this study

Significant medical illness that in the investigator’s opinion cannot be adequately controlled with appropriate therapy or would compromise the patient’s ability to tolerate study treatment

Congestive heart failure (New York Heart Association (NYHA) class 3+4); uncontrolled angina pectoris; poorly controlled hypertension (systolic BP > 180 mmHg or diastolic BP > 100 mmHg); or high-risk uncontrollable arrhythmias.

Patients with severe dyspnoea at rest due to complications of advanced malignancy or requiring supplementary oxygen therapy.

Patients with known hypersensitivity to trastuzumab or any of the study drugs, murine proteins, or to any of the excipients

Symptomatic brain metastases uncontrolled by corticosteroids or carcinomatous meningitis

Homozygosity or compound heterozygosity for more than one gene variant of dihydropyrimidine dehydrogenase (DPD) known to cause major reduced metabolism of 5-FU derivates OR plasma uracil > 150 ng/ml are not eligible. Patients with minor DPD insufficiency are allowed provided that local guidelines for administration of 5-FU are followed.

Any other cancer (excluding low risk prostate cancer, carcinoma in situ and radically operated localised squamous skin cancer) with clinical activity within the last 2 years

Other current cancer treatments except for anti-hormone and anti-resorptive treatment of bone metastasis.

Study & Design

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

Primary Outcome Measures

Name	Time	Method
If response in 12 out of 24 patients, the alternative hypothesis is accepted, and the drug is considered appropriate for further evaluation.		If response in 12 out of 24 patients, the alternative hypothesis is accepted, and the drug is considered appropriate for further evaluation.

Trial Locations

Locations (4)

Rigshospitalet; 🇩🇰 Copenhagen Oe, Denmark

Aarhus Universitetshospital; 🇩🇰 Aarhus N, Denmark

Aalborg University Hospital; 🇩🇰 Aalborg, Denmark

Odense University Hospital; 🇩🇰 Odense C, Denmark

Rigshospitalet

🇩🇰Copenhagen Oe, Denmark

Lene Jensen

Site contact

35458471

lene.baeksgaard.jensen@regionh.dk