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Trial record 2 of 172 for:    pertuzumab

Feasibility Study of Chemoradiation, TRAstuzumab and Pertuzumab in Resectable HER2+ Esophageal Carcinoma (TRAP)

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ClinicalTrials.gov Identifier: NCT02120911
Recruitment Status : Completed
First Posted : April 23, 2014
Last Update Posted : May 31, 2017
Sponsor:
Collaborator:
Roche Pharma AG
Information provided by (Responsible Party):
H.W.M. van Laarhoven, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Brief Summary:
Despite neoadjuvant chemoradiation regimens esophageal cancer remains a disease with poor outcome. The clinical benefit of HER2 targeting with trastuzumab has been shown in the setting of advanced disease and disease and safety of combining trastuzumab with chemoradiation in the curative setting has been established. In breast cancer, the added value of pertuzumab to standard treatment with trastuzumab has been shown both in the neoadjuvant and the metastastic setting. Taken together, there is a sound rationale to explore the combination of radiotherapy plus chemotherapy with trastuzumab and pertuzumab in HER2+resectable esophageal cancer. However, since the number of HER2+ patients in this setting is limited, and no data are available on the safety of this combination prior to major surgery, we propose to first conduct a feasibility study with this treatment stratgy. When the results of this study show that this treatment strategy is feasible, we will subsequently design a prospective study with efficacy as primary endpoint.

Condition or disease Intervention/treatment Phase
Esophageal Carcinoma Drug: Pertuzumab, trastuzumab Phase 1 Phase 2

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Feasibility Study of Chemoradiation, TRAstuzumab and Pertuzumab in Resectable HER2+Esophageal Carcinoma: the TRAP Study
Study Start Date : January 2014
Actual Primary Completion Date : February 2017
Actual Study Completion Date : February 2017

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Pertuzumab, trastuzumab
Pertuzumab, trastuzumab
Drug: Pertuzumab, trastuzumab
Pertuzumab and trastuzumab will be combined with standard chemoradiation with carboplatin and paclitaxel.
Other Names:
  • Perjeta
  • Herceptin




Primary Outcome Measures :
  1. % of patients completing trastuzumab and pertuzumab treatment. [ Time Frame: up to 14 weeks after start of treatment ]
    See title


Secondary Outcome Measures :
  1. Toxicity of pertuzumab and trastuzumab alone and in combination with chemoradiation [ Time Frame: up to 14 weeks after start of treatment ]
  2. Number of post-operative complications [ Time Frame: up to 3 months after surgery ]
  3. Pathological response [ Time Frame: up to 2 weeks after surgery ]
  4. R0 resection rate [ Time Frame: up to 2 weeks after surgery ]
  5. Pharmacokinetics of pertuzumab and trastuzumab [ Time Frame: up to 14 weeks after start of treatment ]

Other Outcome Measures:
  1. Relation between exposure and effect (safety and efficacy). [ Time Frame: up to 3 months after surgery ]
  2. Biomarker analyses [ Time Frame: up to 3 months after surgery ]
  3. SUV of pre-treatment trastuzumab-PET [ Time Frame: up to two weeks after surgery ]


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02120911


Locations
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Netherlands
Academic Medical Center, Medical Oncology
Amsterdam, Netherlands, 1100 DD
Sponsors and Collaborators
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Roche Pharma AG
Investigators
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Principal Investigator: H. WM van Laarhoven, MD, PhD, PhD Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

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Responsible Party: H.W.M. van Laarhoven, MD, PhD, PhD, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
ClinicalTrials.gov Identifier: NCT02120911     History of Changes
Other Study ID Numbers: AMCMEDONC 2013-377
2013-004111-42 ( EudraCT Number )
First Posted: April 23, 2014    Key Record Dates
Last Update Posted: May 31, 2017
Last Verified: May 2017
Keywords provided by H.W.M. van Laarhoven, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA):
Her2+
Resectable esophageal carcinoma
Pertuzumab
Trastuzumab
Additional relevant MeSH terms:
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Pertuzumab
Carcinoma
Esophageal Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Head and Neck Neoplasms
Digestive System Diseases
Esophageal Diseases
Gastrointestinal Diseases
Trastuzumab
Antineoplastic Agents, Immunological
Antineoplastic Agents