HER2 positive Esophageal Squamous Cell Carcinoma MedDRA version: 21.0 Level: LLT Classification code 10041824 Term: Squamous cell carcinoma of esophagus System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 21.0 Level: LLT Classification code 10041825 Term: Squamous cell carcinoma of esophagus NOS System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 21.0 Level: LLT Classi
Conditions
Interventions
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: Trastuzumab
CAS Number: 180288-69-1
Concentration unit: mg/kg milligram(s)/kilogram
Concentration type: range
Concentration number: 6-8
Sponsors
Department of Oncology, Rigshospitalet
Eligibility
Sex/Gender
All
Inclusion criteria
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 rate =2 or IHC3+ 5. ECOG PS 50% measured by echocardiography or MUGA 7. Adequate bone marrow function and organ function: a. Hematopoietic function: b. Leucocytes > 3.0 x 109/l, neutrocytes > 1.5 x 109/l and thrombocytes > 100 x 109/l c. Serum bilirubin 30 ml/min Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 24 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 24
Exclusion criteria
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 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) (iRECIST).;Secondary Objective: Determine partial, complete and overall response rate according to iRECIST and RECIST 1.1 and overall survival (OS) in patients with ESCC treated with trastuzumab added to standard treatment (fluoropyrimidine/platinum doublet with/without pembrolizumab) Evaluate safety and tolerability of trastuzumab, pembrolizumab and a fluoropyrimidine/platinum doublet. Evaluate clinical utility of measurements of amplified HER2 in ctDNA as a monitoring tool Evaluate the predictive value of Fc Gamma Receptor polymorphisms in ESCC patients receiving trastuzumab, pembrolizumab and a fluoropyrimidine/platinum doublet. Evaluate PD-L1 status by CPS score and other putative predictive factors for efficacy and immune-related response. Evaluate the prevalence and status of HER2 IHC and ISH and its clinical utility. Investigate concordance between HER2 status assessed by immunohistochemistry, in-situ hybridization, copy number variants with DNA sequencing, RNA sequencing and by amplified HER2 in ctDNA ;Primary end point(s): 6 months progression free survival (PFS);Timepoint(s) of evaluation of this end point: This is a simons minmax two stage trial. An interim analysis is planned after stage 1. Decision to go to stage 2 will be made by consensus among investigators. A decision will be made to proceed to stage 2 if 7 patients out of 17 patients achieve a 6 months PFS according to iRECIST. Time of interim analysis and final analysis will depend upon patient accrual, the study is expected to have 30 months accrual and 6 months follow-up. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Response rate according to iRECIST • Response rate according to RECIST 1.1 • Six months OS • Median PFS and OS • Time to progression • Common Terminology Criteria for Adverse Events (CTCAEs) version 5.0 ;Timepoint(s) of evaluation of this end point: This is a simons minmax two stage trial. An interim analysis is planned after stage 1. Decision to go to stage 2 will be made by consensus among investigators. A decision will be made to proceed to stage 2 if 7 patients out of 17 patients achieve a 6 months PFS according to iRECIST. Time of interim analysis and final analysis will depend upon patient accrual, the study is expected to have 30 months accrual and 6 months follow-up. | — |
Countries
Denmark
Contacts
Public ContactMorten Mau-Sørensen
Department of Oncology, Rigshospitalet
Outcome results
None listed