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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Rigshospitalet, Frederiksberg Hospital

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

21 Feb 2022 → ongoing

Decision date (initial)

2024-11-29

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-516318-40-02

EudraCT number

2021-003415-26

ClinicalTrials.gov

NCT05170256

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

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).

Conditions and MedDRA coding

Esophageal Cancer

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. 1. Signed informed consent
2. 2. Age ≥18 years
3. Inoperable locally advanced or metastatic squamous cell carcinoma of the esophagus not amenable for curative intended therapy
4. 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+
5. ECOG PS <2
6. Baseline left ventricular ejection fraction > 50% measured by echocardiography or MUGA
7. 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 13

1. Prior systemic treatment with non-curative intent including HER2-targeting drugs. Prior neoadjuvant and adjuvant therapies as well as palliative radiotherapy are allowed
2. 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
3. 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.
4. Patients with severe dyspnoea at rest due to complications of advanced malignancy or requiring supplementary oxygen therapy.
5. Patients with known hypersensitivity to trastuzumab or any of the study drugs, murine proteins, or to any of the excipients
6. Symptomatic brain metastases uncontrolled by corticosteroids or carcinomatous meningitis
7. 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.
8. 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
9. Other current cancer treatments except for anti-hormone and anti-resorptive treatment of bone metastasis.
10. Allopurinol, phenytoin, warfarin treatment is not allowed. Non vitamin K oral anticoagulants (NOAK) and low molecular weight (LMW) heparin is allowed
11. Pregnancy or breast-feeding
12. Positive serum pregnancy test in women of childbearing potential
13. Subjects with reproductive potential not willing to use an effective method of contraception under and 3 months after participation in this study

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

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

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 6

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Rigshospitalet

Sponsor organisation

Rigshospitalet

Address

Blegdamsvej 9

City

Copenhagen Oe

Postcode

2100

Country

Denmark

Scientific contact point

Organisation

Rigshospitalet

Contact name

Paul Morten Mau-Sørensen

Public contact point

Organisation

Rigshospitalet

Contact name

Paul Morten Mau-Sørensen

Third parties 1

Frederiksberg Hospital

Sponsor organisation

Frederiksberg Hospital

Address

Nordre Fasanvej 57, 1st Floor Entrance 2 1st Floor Entrance 2

City

Frederiksberg

Postcode

2000

Country

Denmark

Third parties 1

Sponsor responsibilities

Article 77 compliance

Rigshospitalet

Contact point sponsor

Rigshospitalet

Article 77 implementation

Rigshospitalet

Locations

1 EU/EEA country · 4 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 11 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications