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

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
78

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • 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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

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

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
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

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
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

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • 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)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 1, 2010

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
February 1, 2011

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
April 1, 2012

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
February 25, 2010

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 1, 2010

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
March 2, 2010

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
April 21, 2021

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 19, 2021

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
April 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant 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.

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