- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02120911
Feasibility Study of Chemoradiation, TRAstuzumab and Pertuzumab in Resectable HER2+ Esophageal Carcinoma (TRAP)
Feasibility Study of Chemoradiation, TRAstuzumab and Pertuzumab in Resectable HER2+Esophageal Carcinoma: the TRAP Study
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Objective of the study:
Assess the feasibility of preoperative treatment with pertuzumab and trastuzumab combined with preoperative chemoradiation (carboplatin, paclitaxel and radiation) in terms of withdrawal rate from surgery.
Study design:
This is a non-randomized feasibility study with Paclitaxel (T), Carboplatin (C), Pertuzumab (P). Trastuzumab (H), and radiation (RT) followed by surgical resection of the oesophagus.
Study population:
Patients (male/female) with histologically proven adenocarcinoma of the intrathoracic esophagus or gastro esophageal junction, age >18 and <75 years.
Intervention (if applicable):
Paclitaxel 50 mg/m2 and Carboplatin AUC = 2 will be given by intravenous infusion on days 1, 8, 15, 22 and 29.
Trastuzumab will be administered at a dose of 4 mg/kg on day 1, followed by 2 mg/kg at wk 2-6. From wk 7 onwards trastuzumab is administered at a dose of 6 mg/kg every 3 weeks. Pertuzumab will be given 840 mg intravenously at each administration.
Thus, trastuzumab and pertuzumab will be continued during eight weeks after the end of chemoradiation. Surgery will be planned in or around week 14, approximately eight weeks after the end of chemoradiation.
Study Type
Enrollment (Actual)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Locations
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-
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Amsterdam, Netherlands, 1100 DD
- Academic Medical Center, Medical Oncology
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Histologically proven adenocarcinoma of the intrathoracic esophagus or gastro esophageal junction.
- HER2-positive tumor defined as either IHC 3+ or IHC 2+, the latter in combination with ISH+, as assessed by the sponsor-designated central laboratory (pathology AMC) on a primary tumor biopsy.
- Surgical resectable (T2-3, N0-1, M0), as determined by Endoscopic Ultra Sound (EUS) and CT scan of neck, thorax and abdomen.
- T1N1 tumors are eligible, T1N0 tumors and in situ carcinoma are not eligible.
- Tumor length longitudinal ≤ 10 cm and radial ≤ 5 cm.
- If tumor extends below the gastroesophageal (GE) junction into the proximal stomach, the bulk of the tumor must involve the esophagus or GE junction. The tumor must not extend more than 2 cm into the stomach.
- No invasion of the tracheobronchial tree or presence of tracheoesophageal fistula.
- Age ≥ 18 and ≤ 75 years.
- ECOG performance status 0 or 1.
Adequate hematological, renal and hepatic functions defined as:
- neutrophiles ≥ 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%.
- Written, voluntary informed consent.
- Patients must be accessible to follow up and management in the treatment center.
Exclusion Criteria:
- A tumour the epicenter of which in the stomach is greater than 5 cm of the GE junction or those within 5 cm of the GE junction without extension in the oesophagus are classified as gastric cancer.
- Past or current history of malignancy other than entry diagnosis except for non-melanomatous skin cancer, or curatively treated in situ carcinoma of the cervix, or malignancy more than 5 years prior to enrollment.
- Pregnancy (positive serum pregnancy test), planning to become pregnant, and lactation.
- Patient (male or female) is not willing to use highly effective methods of contraception (per institutional standard) during treatment and for 6 months (male or female) after the end of treatment.
- Previous chemotherapy, radiotherapy, treatment with an anti-HER2 antibody or with small molecule HER2 inhibitors.
- Clinically significant cardiovascular disease (including myocardial infarction, unstable angina, symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia) ≤ 1 year before randomization.
- Pulmonary fibrosis and/or severely impaired lung function.
- Pre-existing motor or sensory neurotoxicity greater than WHO grade 1.
- Active infection or other 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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Pertuzumab, trastuzumab
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Pertuzumab and trastuzumab will be combined with standard chemoradiation with carboplatin and paclitaxel.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
% of patients completing trastuzumab and pertuzumab treatment.
Time Frame: up to 14 weeks after start of treatment
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See title
|
up to 14 weeks after start of treatment
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Toxicity of pertuzumab and trastuzumab alone and in combination with chemoradiation
Time Frame: up to 14 weeks after start of treatment
|
See title
|
up to 14 weeks after start of treatment
|
Number of post-operative complications
Time Frame: up to 3 months after surgery
|
See title
|
up to 3 months after surgery
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Pathological response
Time Frame: up to 2 weeks after surgery
|
See title
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up to 2 weeks after surgery
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R0 resection rate
Time Frame: up to 2 weeks after surgery
|
See title
|
up to 2 weeks after surgery
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Pharmacokinetics of pertuzumab and trastuzumab
Time Frame: up to 14 weeks after start of treatment
|
See title
|
up to 14 weeks after start of treatment
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Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Relation between exposure and effect (safety and efficacy).
Time Frame: up to 3 months after surgery
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See title
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up to 3 months after surgery
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Biomarker analyses
Time Frame: up to 3 months after surgery
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See title
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up to 3 months after surgery
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SUV of pre-treatment trastuzumab-PET
Time Frame: up to two weeks after surgery
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See title
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up to two weeks after surgery
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Collaborators and Investigators
Collaborators
Investigators
- Principal Investigator: H. WM van Laarhoven, MD, PhD, PhD, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Publications and helpful links
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Digestive System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Neoplasms by Site
- Neoplasms, Glandular and Epithelial
- Gastrointestinal Neoplasms
- Digestive System Neoplasms
- Gastrointestinal Diseases
- Head and Neck Neoplasms
- Esophageal Diseases
- Carcinoma
- Esophageal Neoplasms
- Antineoplastic Agents
- Antineoplastic Agents, Immunological
- Trastuzumab
- Pertuzumab
Other Study ID Numbers
- AMCMEDONC 2013-377
- 2013-004111-42 (EudraCT Number)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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