TRAstuzumab and Pertuzumab for HER2+ Resectable Oesophageal Cancer

Esophageal Cancer Clinical Trial

— TRAP-2  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05188313
• Other study ID #: NL79276.018.21
• Status: Recruiting
• Phase: Phase 3
• Start date: March 9, 2022
• Est. completion date: February 2037

Study information

• Verified date: June 2022
• Source: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Despite treatment according to the CROSS-regimen, median overall survival is less than four years (2.3 QALYs). The burden of disease is within the highest category (0.71 to 1.0). Also, no targeted treatment options are currently available, hampering personalized treatment for this patient population. TRAP-2 aims to address these needs by investigating whether addition of trastuzumab and pertuzumab to standard of care improves survival of patients with resectable HER2 positive esophageal adenocarcinoma (HER2+ EAC). Patients with HER2+ EAC will be randomised to neoadjuvant chemoradiation according to the CROSS regimen or CROSS + TRAstuzumab and Pertuzumab. Primary outcome is overall survival.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 376
• Est. completion date: February 2037
• Est. primary completion date: July 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 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.

• ECOG performance status 0 or 1 (cf. Appendix A).

• Adequate hematological, renal and hepatic functions defined as:

• Neutrophils = 1.5 x 109/L

• Platelets = 100 x 109/L

• Hemoglobin = 5.6 mmol

• Total bilirubin = 1.5 x upper normal limit

• Creatinine clearance (Cockroft) > 60 ml/min

• Adequate left ventricular ejection fraction defined as an LVEF of =55% 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:

• 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.

• 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.

Related Conditions & MeSH terms

• Adenocarcinoma
• Esophageal Adenocarcinoma
• Esophageal Cancer

Intervention

Drug:
• Trastuzumab
Intravenous administration of study drug
• Pertuzumab
Intravenous administration of study drug
• Paclitaxel
Intravenous administration of study drug
• Carboplatin
Intravenous administration of study drug

Locations

Country	Name	City	State
Netherlands	Academic Medical Center	Amsterdam

Sponsors (1)

Lead Sponsor	Collaborator
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall survival	Overall survival will be calculated from the date of randomization to death.	5.5. years (maximum follow-up time)
Secondary	Progression free survival	Progression free survival will be calculated from the date of randomization to death or progression.	5.5. years (maximum follow-up time)
Secondary	Adverse events	Treatment toxicity according	15 weeks (duration of neoadjuvant treatment)
Secondary	Surgical complications	Surgical complications according to Clavien Dindo	30 days after surgery
Secondary	Left Ventricular Systolic Dysfunction	= 10 percentage points decrease from baseline to an absolute value < 50%	5.5. years
Secondary	General quality of life	Quality of life	5.5. years