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.
- Conditions
- Esophageal Cancer10017991
- Registration Number
- NL-OMON54165
- Lead Sponsor
- Academisch Medisch Centrum
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 388
- 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: 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
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
- 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.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>The primary outcome is overall survival.</p><br>
- Secondary Outcome Measures
Name Time Method <p>Secondary outcome measures are quality of life adjusted survival,<br /><br>progression-free survival and pathological response, safety and quality of life.<br /><br>Survival measures are determined up to a maximum follow-up period of 5.5 years.<br /><br>Quality of life is assessed before initiation of treatment and then every three<br /><br>months in the first year, every 6 months in the second year and annually<br /><br>thereafter.<br /><br>Chemotherapy side effects are determined immediately after the end of treatment<br /><br>and serious side effects are reported immediately.<br /><br>Pathological response is assessed by the pathologist according to the so-called<br /><br>Mandard criteria immediately after surgery.</p><br>