Chemoradiation and Panitumumab for Esophageal Cancer

April 19, 2021 updated by: J.W. Wilmink, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Chemoradiation Combined With Panitumumab Followed by Surgery for Patients With Operable Esophageal Cancer

A consistent finding in many studies in patients with operable esophageal and gastro-esophageal junction (GEJ) cancer is that response to preoperative therapy, particularly the absence of residual disease in the surgical specimen, is an indicator of better disease-free and overall survival. Therefore in the investigators trial the investigators will evaluate the pathologic response of panitumumab in combination with neoadjuvant chemoradiation as first line treatment of operable adenocarcinomas, undifferentiated or squamous cell carcinomas of the esophagus.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

This is a Phase II, non-randomized trial. Eligible subjects will be treated with panitumumab plus carboplatin, paclitaxel and radiotherapy followed by surgical resection of the esophagus.

Panitumumab administration schedule: Panitumumab will be administered as a 60-minute ± 15 minutes IV infusion, prior to administration of chemotherapy at a dose of 6 mg/kg on day 1, 15 and 29. If the first infusion is well tolerated (without any serious infusion related reactions) all subsequent infusions may be administered over 30 minutes ± 10 minutes.

Chemotherapy regimen: Paclitaxel 50 mg/m2 and Carboplatin AUC = 2 will be given by intravenous infusion on days 1, 8, 15, 22 and 29. Both drugs will be infused over one hour.

Radiotherapy treatment: A total dose of 41.4 Gy will be given in 23 fractions of 1.8 Gy, 5 fractions per week, starting the first day of the first cycle of chemotherapy. All patients will be radiated by external beam radiation, using 3-D conformal radiation technique.

Surgery: Surgery will be performed preferably within 6 weeks after the completion of the chemoradiation and panitumumab. For carcinomas distal of the tracheal bifurcation but proximal to the gastro-esophageal junction, a transthoracic approach is preferred. For distal tumors involving the gastro-esophageal junction a transhiatal esophageal resection is preferred. A wide local excision including the N1 lymph nodes is carried out in both techniques including a standard excision of the lymph nodes around the coeliac axis. The continuity of the digestive tract will be restored by a gastric tube reconstruction or colonic interposition procedure with an anastomosis in the neck.

Study Type

Interventional

Enrollment (Actual)

78

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Netherlands
      • Amsterdam, Netherlands, 1105 AZ
        • Academic Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Histologically proven squamous cell carcinoma, adenocarcinoma or undifferentiated carcinoma of the intrathoracic esophagus or gastro esophageal junction
  • 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. Gastric cancers with minor involvement of the GE junction or distal esophagus are not eligible
  • No invasion of the tracheobronchial tree or presence of tracheoesophageal fistula
  • Non pregnant, non-lactating female patients, not planning to become pregnant within 6 months after the end of treatment.
  • Age ≥ 18 and ≤ 75
  • ECOG performance status 0 or 1
  • Adequate hematological, renal, hepatic and pulmonary functions
  • Written, voluntary informed consent
  • Patients must be accessible to follow up and management in the treatment center

Exclusion Criteria:

  • 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) 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-EGFR antibody or with small molecule EGFR inhibitors
  • Clinically significant cardiovascular disease (including myocardial infarction, unstable angina, symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia) ≤ 1 year before randomization
  • Pulmonary fibrosis
  • 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
  • Weight loss > 15%.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Carboplatin + paclitaxel + radiotherapy
Carboplatin AUC = 2, Paclitaxel 50 mg/m2 (both weekly) , a total dose of 41.4 Gy will be given in 23 fractions of 1.8 Gy.
Drug: Carboplatin
Carboplatin AUC = 2 , weekly.
Drug: Paclitaxel
Paclitaxel 50 mg/m2, weekly
Radiation: radiotherapy
A total dose of 41.4 Gy will be given in 23 fractions of 1.8 Gy.
Experimental: Carboplatin+ paclitaxel+ panitumumab+ radiotherapy
Carboplatin AUC = 2, Paclitaxel 50 mg/m2 (both weekly) , a total dose of 41.4 Gy will be given in 23 fractions of 1.8 Gy. Panitumumab panitumumab: 6mg/kg in weeks 1-3-5.
Drug: Carboplatin
Carboplatin AUC = 2 , weekly.
Drug: Paclitaxel
Paclitaxel 50 mg/m2, weekly
Radiation: radiotherapy
A total dose of 41.4 Gy will be given in 23 fractions of 1.8 Gy.
Drug: panitumumab
panitumumab: 6mg/kg in weeks 1-3-5.
Other Names:
  • vectibix

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Percentage of pathologic complete responses
Time Frame: 6 weeks after the completion of the chemoradiation
6 weeks after the completion of the chemoradiation

Secondary Outcome Measures

Outcome Measure
Time Frame
R0 resection rate
Time Frame: the pathologist will determine the resection rate
the pathologist will determine the resection rate
Progression free survival
Time Frame: Every 3 months during the first 2 years after surgery, and every 6 months thereafter.
Every 3 months during the first 2 years after surgery, and every 6 months thereafter.
Toxicity profile
Time Frame: Weekly during chemoradiation. After surgery: every 3 months during the first 2 years after surgery, and every 6 months thereafter.
Weekly during chemoradiation. After surgery: every 3 months during the first 2 years after surgery, and every 6 months thereafter.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Investigators

  • Principal Investigator: Hanneke Wilmink, MD PhD, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 1, 2010

Primary Completion (Actual)

February 1, 2011

Study Completion (Actual)

April 1, 2012

Study Registration Dates

First Submitted

February 25, 2010

First Submitted That Met QC Criteria

March 1, 2010

First Posted (Estimate)

March 2, 2010

Study Record Updates

Last Update Posted (Actual)

April 21, 2021

Last Update Submitted That Met QC Criteria

April 19, 2021

Last Verified

April 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • AMCmedon08/381

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.

Clinical Trials on Adenocarcinoma

Clinical Trials on Carboplatin

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Zimbabwe

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe