Trastuzumab and Standard Treatment With Chemo- and Immunotherapy as First Line Treatment for HER2 Positive Esophageal Squamous Cell Carcinoma Patients

Esophageal Squamous Cell Carcinoma Clinical Trial

— HERES  

Official title:

HERES Trial: Trastuzumab and Standard Treatment With Chemo- and Immunotherapy as First Line Treatment for HER2 Positive Esophageal Squamous Cell Carcinoma Patients

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05170256
• Other study ID #: 2021-003415-26
• Status: Recruiting
• Phase: Phase 2
• Start date: February 4, 2022
• Est. completion date: January 2025

Study information

• Verified date: August 2022
• Source: Rigshospitalet, Denmark
• Contact: Morten Mau-Sørensen, MD PhD
• Phone: 35450879
• Email: paul.morten.mau-soerensen[@]regionh.dk
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The study aims to determine the efficacy of trastuzumab added to standard treatment (fluoropyrimidine/platinum doublet with pembrolizumab) in patients with HER2 positive Esophageal squamous cell carcinoma (ESCC) determined by 6 months progression free survival (PFS) (RECIST 1.1).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 24
• Est. completion date: January 2025
• Est. primary completion date: January 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Signed informed consent

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 IHC2+ and FISH amplification ratio =2 or 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:

1. Hematopoietic function:

2. Leucocytes > 3.0 x 109/l, neutrocytes > 1.5 x 109/l and thrombocytes > 100 x 109/l

3. Serum bilirubin < 1.5 × upper limit of normal (ULN); and AST/ALT < 2.5 × ULN (or < 5 × ULN in patients with liver metastases).

8. Creatinine clearance > 30 ml/min

Exclusion Criteria:

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

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Squamous Cell
• Esophageal Squamous Cell Carcinoma
• HER-2 Gene Amplification
• HER-2 Protein Overexpression

Intervention

Drug:
• Trastuzumab
Addition of trastuzumab to standard treatment (fluoropyrimidine/platinum doublet with pembrolizumab)

Locations

Country	Name	City	State
Denmark	Dept of Oncology, Rigshospitalet	Copenhagen	Region H
Denmark	Onkologisk Afdeling R, Odense University Hospital	Odense	Region Syd

Sponsors (4)

Lead Sponsor	Collaborator
Morten Mau-Sørensen	Aalborg University Hospital, Aarhus University Hospital, Odense University Hospital

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Change in amplified HER2 in ctDNA during treatment	Clinical utility of measurements of amplified HER2 in ctDNA as a monitoring tool of treatment with 5-FU platinum, trastuzumab and pembrolizumab	During mininum 6 months follow-up
Other	Frequency of germeline Fc Gamma Receptor polymorphisms	Predictive value of Fc Gamma Receptor polymorphisms in ESCC patients receiving	During minimum 6 months follow-up
Other	Frequency of PD-L1 status by CPS score	PD-L1 status by CPS score	During minimum 6 months follow-up
Primary	Progression free survival (PFS) .	PFS according to RECIST 1.1	6 months
Secondary	Response rate according to RECIST 1.1	Partial, complete and overall response rate according to RECIST 1.1	Best response during 6 months follow-up
Secondary	Frequency of AEs assessed by NCI CTCAE, v. 5.0	Safety and tolerability of trastuzumab, pembrolizumab and a fluoropyrimidine/platinum assessed by NCI CTCAE, v. 5.0	During minimum 6 months follow-up
Secondary	Overall survival	Time to death of all causes	6 months