Using trastuzumab and pertuzumab to improve survival in HER2+ esophageal cancer
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
This study is testing if adding two targeted therapies, trastuzumab and pertuzumab, to standard treatment can help people with HER2-positive esophageal cancer live longer.
Quick facts
| Phase | Phase 3 |
|---|---|
| Study type | Interventional |
| Enrollment | 376 (estimated) |
| Ages | 18 Years and up |
| Sex | All |
| Sponsor | Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) Academic / other |
| Drugs / interventions | chemotherapy, radiation, trastuzumab, pertuzumab |
| Locations | 1 site (Amsterdam) |
| Trial ID | NCT05188313 on ClinicalTrials.gov |
What this trial studies
This clinical trial investigates the effectiveness of adding trastuzumab and pertuzumab to the standard neoadjuvant chemoradiation treatment for patients with resectable HER2-positive esophageal adenocarcinoma. Participants will be randomized to receive either the standard CROSS regimen or the CROSS regimen plus the targeted therapies. The primary goal is to determine if this combination improves overall survival rates compared to the standard treatment alone. The study aims to address the lack of targeted treatment options for this patient population.
Who should consider this trial
Good fit: Ideal candidates include adults aged 18 and older with histologically confirmed HER2-positive esophageal adenocarcinoma who are eligible for surgical resection.
Not a fit: Patients with non-resectable tumors or those with HER2-negative esophageal cancer may not benefit from this study.
Why it matters
Potential benefit: If successful, this approach could significantly improve survival outcomes for patients with HER2-positive esophageal adenocarcinoma.
How similar studies have performed: Other studies have shown promising results with targeted therapies in HER2-positive cancers, suggesting potential success for this approach.
Eligibility criteria
Show full inclusion / exclusion criteria
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.
Where this trial is running
Amsterdam
- Academic Medical Center — Amsterdam, Netherlands (Recruiting)
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.