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

NCT05170256 | Unknown Phase 2 DMC

• 1 other identifier: 2021-003415-26
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 2

Brief 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).

Conditions

Esophageal Squamous Cell Carcinoma; HER-2 Protein Overexpression; HER-2 Gene Amplification

Outcome Measures

Primary Outcomes (1)

• Progression free survival (PFS) .

  PFS according to RECIST 1.1

  6 months

Secondary Outcomes (3)

• Response rate according to RECIST 1.1

  Best response during 6 months follow-up

• Frequency of AEs assessed by NCI CTCAE, v. 5.0

  During minimum 6 months follow-up

• Overall survival

  6 months

Other Outcomes (3)

• Change in amplified HER2 in ctDNA during treatment

  During mininum 6 months follow-up

• Frequency of germeline Fc Gamma Receptor polymorphisms

  During minimum 6 months follow-up

• Frequency of PD-L1 status by CPS score

  During minimum 6 months follow-up

Study Arms (1)

Treatment arm

EXPERIMENTAL

Drug: Trastuzumab

Interventions

Trastuzumab DRUG

Addition of trastuzumab to standard treatment (fluoropyrimidine/platinum doublet with pembrolizumab)

Treatment arm

Eligibility Criteria

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

You may qualify if:

• Signed informed consent
• Age ≥18 years
• Inoperable locally advanced or metastatic squamous cell carcinoma of the esophagus not amenable for curative intended therapy
• HER2 positive defined as IHC2+ and FISH amplification ratio ≥2 or IHC3+
• ECOG PS \<2
• Baseline left ventricular ejection fraction \> 50% measured by echocardiography or MUGA
• Adequate bone marrow function and organ function:
• Hematopoietic function:
• Leucocytes \> 3.0 x 109/l, neutrocytes \> 1.5 x 109/l and thrombocytes \> 100 x 109/l
• Serum bilirubin \< 1.5 × upper limit of normal (ULN); and AST/ALT \< 2.5 × ULN (or \< 5 × ULN in patients with liver metastases).
• Creatinine clearance \> 30 ml/min

You may not qualify if:

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

Sponsors & Collaborators

• Morten Mau-Sørensen: lead
• Odense University Hospital: collaborator
• Aalborg University Hospital: collaborator
• Aarhus University Hospital: collaborator

Study Sites (2)

Dept of Oncology, Rigshospitalet

Copenhagen, Region H, DK-2100, Denmark

RECRUITING

Onkologisk Afdeling R, Odense University Hospital

Odense, Region Syd, 5000, Denmark

RECRUITING

MeSH Terms

Conditions

Esophageal Squamous Cell Carcinoma

Interventions

Trastuzumab

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Squamous Cell; Esophageal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Lene Baeksgaard, MD PhD

  Rigshospitalet, Denmark

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Morten Mau-Sørensen, MD PhD

CONTACT

35450879; paul.morten.mau-soerensen@regionh.dk

Kristian Egebjerg, MD

CONTACT

kristian.egebjerg.02@regionh.dk

Study Design

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

Model Details: The study is a two-staged single arm national phase II trial * Stage 1: 17 patients * Stage 2: 7 patients

Study Record Dates

• First Submitted: November 24, 2021
• First Posted: December 27, 2021
• Study Start: February 4, 2022
• Primary Completion: January 1, 2025
• Study Completion: January 1, 2025
• Last Updated: August 12, 2022

Record last verified: 2022-08

Locations

DK (2)