The efficacy of the addition of TRAstuzumab and Pertuzumab to neoadjuvant chemoradiation: a randomized multi-center study in resectable HER2 overexpressing adenocarcinoma of the esophagus or gastroesophageal junction. The TRAP-2 study

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Amsterdam UMC Stichting

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

9 Mar 2022 → ongoing

Decision date (initial)

2024-11-01

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-513797-22-00

EudraCT number

2021-005328-39

ClinicalTrials.gov

NCT05188313

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Therapy

To investigate whether addition of trastuzumab and pertuzumab to standard of care improves overall survival of patients with resectable HER2 positive esophageal adenocarcinoma (HER2+ EAC).

Conditions and MedDRA coding

HER2 positive esophageal adenocarcinoma

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. - Histologically proven adenocarcinoma of the esophagus or gastroesophageal junction, T1N+M0; or T2-T4a N0 or N+ M0). - HER2-positive tumor defined as either IHC 3+ or IHC 2+, the latter in combination with ISH+, as assessed by the local laboratory on a primary tumor biopsy. HER2 status needs to be confirmed by the central laboratory, but does not affect start of treatment. - Surgical resectability, as determined during multidisciplinary meeting. Tumors that cannot be passed with an endoscope for endoscopic ultrasound are eligible if all other criteria are fulfilled. - If the tumor extends below the gastroesophageal (GE) junction into the proximal stomach, the bulk of the tumor must involve the esophagus or GE junction. - Age ≥ 18. - Patient is fit for esophagectomy.Adequate hematological, renal and hepatic functions defined as: o Neutrophils ≥ 1.5 x 109/L o Platelets ≥ 100 x 109/L o Hemoglobin ≥ 5.6 mmol o Total bilirubin ≤ 1.5 x upper normal limit o Creatinine < 150 μmol l-1 or creatinine clearance (Cockroft) ≥ 50 ml/min - Adequate left ventricular ejection fraction defined as an LVEF of ≥50% determined by transthoracic echocardiography or MUGA. - Written, voluntary informed consent - Patients must be accessible to follow up and management in the treatment center

Exclusion criteria 1

1. - T1N0 tumors or in situ carcinoma. - Past (within 5 years) or current history of malignancy other than entry diagnosis which has a worse expected prognosis than the current esophageal cancer. - Previous chemotherapy, radiotherapy, treatment with an anti-HER2 antibody or with small molecule HER2 inhibitors for esophageal cancer or for any other cancer within 6 months of diagnosis of esophageal cancer. - Previous radiation to the mediastinum precluding full dose radiation of the currently present esophageal tumor. - Invasion of the tracheobronchial tree or presence of tracheoesophageal fistula. - Pregnancy (positive serum pregnancy test), planning to become pregnant, and lactation. - Not willing to use highly effective methods of contraception (per institutional standard) during treatment (male or female) and for 6 months after the end of treatment. - Clinically significant cardiovascular disease (including myocardial infarction, unstable angina, symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia) precluding major surgery. - Pulmonary fibrosis and/or severely impaired lung function (FEV1 < 1,5L) precluding major surgery. - Serious underlying medical condition which would impair the ability of the patient to receive the planned treatment, including prior allergic reactions to drugs containing Cremophor, such as teniposide or cyclosporine. - ECOG performance status 3 or higher (cf. Appendix A) - Dementia or altered mental status that would prohibit the understanding and giving of informed consent - Inadequate caloric- and/or fluid intake despite consultation of a dietician and/or tube feeding. - Evidence of interstitial lung disease or active, non-infectious pneumonitis. - Active infection requiring systemic therapy which has not resolved 3 days (simple infection such as cystitis) to 7 days (severe infection such as pyelonephritis) prior to the first dose of trial treatment. - Evidence of acute or chronic infection with hepatitis B, C or HIV. - History of prior allogeneic stem cell or solid organ transplantation. - Pre-existing motor or sensory neurotoxicity greater than or equal to CTC AE grade 2.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. overall survival

Secondary endpoints 1

1.  Quality-adjusted life years  Progression free survival  Pathological response according to the Mandard criteria  R0 resection rate  Safety in terms of: o Toxicity defined according to CTCAE v5.0 criteria. o Post-operative complications according to the Clavien - Dindo classification.  Percentage completion of chemotherapy and radiation treatment.  Quality of life

Investigational products

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

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Amsterdam UMC Stichting

Sponsor organisation

Amsterdam UMC Stichting

Address

De Boelelaan 1117

City

Amsterdam

Postcode

1081 HV

Country

Netherlands

Scientific contact point

Organisation

Amsterdam UMC Stichting

Contact name

Laurien Verkleij

Public contact point

Organisation

Amsterdam UMC Stichting

Contact name

Laurien Verkleij

Locations

1 EU/EEA country · 31 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 12 files

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

Application history

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