Erbitux Combined With Chemo-radiotherapy in Esophageal Squamous Cell Carcinoma (EXCEL)

February 4, 2011 updated by: Shandong Cancer Hospital and Institute

An Open-labeled Study to Evaluate Efficacy of Combining Erbitux Plus Concurrent Chemo-radiotherapy in Locally Advanced Esophageal Squamous Cell Carcinoma (ESCC)

The purpose of this study is to determine whether the treatment of locally advanced esophageal squamous cell carcinoma (ESCC)with cetuximab in combination with paclitaxel, cisplatin and radiation improve clinical outcomes.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Esophageal cancer is the sixth leading cause of cancer death worldwide.

Over the past 2 decades, well-designed clinical trials have documented the clinical benefits of combination of chemotherapy and radiation for localized esophageal cancer, either as primary therapy or in neoadjuvant setting.

Paclitaxel, a radiation sensitizer, has important single-agent activity in esophageal cancer. Paclitaxel-based chemoradiation has been the framework for the recent Radiation Therapy Oncology Group (RTOG) trials of nonoperative management of esophageal cancer.

Accumulating clinical evidence suggests that epidermal growth factor receptor (EGFR) represents a viable target in the treatment of esophageal cancer. EGFR expression is associated with poor prognosis. Cetuximab, a monoclonal antibody, binds specifically to EGFR on both normal and tumor cells and competitively inhibits the binding of EGF and other ligands, such as transforming growth factor (TGF)-α.

Preclinical models have suggested synergy between cetuximab, paclitaxel, cisplatin and radiation. For patients with locally advanced head and neck cancer, the combination of cetuximab and radiation has demonstrated both response and survival benefit.

With all these, the investigators hypothesize that treatment of locally advanced esophageal squamous cell carcinoma (ESCC)with cetuximab in combination with paclitaxel, cisplatin and radiation may further improve clinical outcomes. This trial results will be important as it may support further studies for setting the new treatment standard for ESCC.

Study Type

Interventional

Enrollment (Actual)

55

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

  • China
    • Shandong
      • Jinan, Shandong, China, 250117
        • Department of Radiation Oncology, Shandong Cancer Hospital and Institute

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 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Inpatients or outpatients, ≥ 18 years of age

  • Histologically confirmed primary (non-recurrent) ESCC fulfilling one of the following criteria (AJCC Staging System)

    • cervical esophageal carcinoma, stage Ⅱ-Ⅲ
    • upper thoracic esophageal carcinoma, stage Ⅱ-Ⅲ, or mid-thoracic esophageal carcinoma, stage Ⅱ-Ⅲ,which is medically unfit for surgery, surgery been refused and patient medically able to tolerate chemo-radiation.
  • Evidence of unidimensional measurable disease as per Response Evaluation Criteria in Solid Tumours (RECIST).
  • ECOG Performance status of 0-1
  • Effective contraception for both male and female patients if the risk of conception exists
  • Adequate bone marrow reserves: neutrophil (ANC) count ≥ 1500 /mm^3, platelet count ≥ 100,000 /mm^3, hemoglobin ≥ 9 g/dl
  • Adequate renal function: serum creatinine ≤ 1.5 mg/dl and/or calculated creatinine clearance ≥ 60 ml/min
  • Adequate hepatic function: bilirubin level ≤ 1.5 x ULN, ASAT & ALST ≤ 1.5 x ULN
  • Tumor tissue available for KRAS biomarker test
  • Signed written informed consent prior to study entry

Exclusion Criteria:

  • Previous chest radiotherapy, systemic chemotherapy, and major esophageal surgery
  • Concurrent chronic systemic immune therapy, targeted therapy not indicated in this study protocol
  • Multiple primary carcinomas of the esophagus
  • Pregnancy (confirmed by serum or urine β-HCG) or lactation period;
  • Uncontrolled diabetes, hypertension, and severe cardiac or pulmonary disease
  • Unable to comprehend the study requirements or who are not likely to comply with the study parameters;
  • Distant metastasis
  • Second malignancy, except for curable non-melanoma skin cancer, cervical cancer in situ, or malignant disease, free for ≥ 5 years
  • Known grade 3 or 4 allergic reaction to any of the study treatment

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: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: cetuximab, concurrent chemo-radiotherapy
Cetuximab, injection, loading dose400 mg/m^2,(Day1 in Week1) followed by 250 mg/m^2(Day1, every week for Weeks 2-8) Paclitaxel, injection,45 mg/m^2 (Day 1, every week for Weeks 2-8) Cisplatin, injection,20 mg/m^2 (Day 1, every week for Weeks 2-8) radiation therapy, 59.4 Gy, 1.8 Gy/33 fractions,1 fraction daily, Days 1-5 every week for Weeks 2-7, and Days 1-3 for Week 8
Drug: cetuximab (Erbitux)
Cetuximab,injection,loading dose400 mg/m^2,(Day1 in Week1) followed by 250 mg/m^2(Day1, every week for Weeks 2-8)
Other Names:
  • erbitux
Drug: Paclitaxel
Paclitaxel,injection,loading dose 45 mg/m^2,(Day1 in every week for Weeks 2-8)
Drug: Cisplatin
Cisplatin,injection,loading dose 20 mg/m^2,(Day1 in every week for Weeks 2-8)
Radiation: Radiation
Radiation, External beam therapy, total 59.4 Gy , 33 fractions, 1.8 Gy per fraction.(Day 1-Day 5 in every week 2-week 8).
Other Names:
  • Conformal Radiotherapy
  • Intensity Modulated Radiotherapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants With Overall Response Rate (RR)
Time Frame: 1 to 3 month after therapy
The overall response rate was defined as the numbers of patients with a complete response (CR) or partial response (PR). CR was defined as no target lesion at follow-up computed tomography scan and barium swallow examination 3-6 weeks after completion of chemo-radiation. PR was defined at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
1 to 3 month after therapy

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants With Toxicity
Time Frame: Every week during treatment and 1 month after therapy
All patients were regularly monitored for possible adverse events, which were graded according to National Cancer Institute Common Toxicity Criteria version 3.0.
Every week during treatment and 1 month after therapy
Participants With Overall Survival (OS) at 1 Year
Time Frame: 1 year from the date of diagnosis
1 year from the date of diagnosis
Participants With Overall Survival (OS) at 3 Year
Time Frame: 3 year from the date of diagnosis
3 year from the date of diagnosis
Participants With Progression Free Survival (PFS)
Time Frame: Recurrence or metastasis from the date of diagnosis
Recurrence or metastasis from the date of diagnosis
Number of Participants With K-ras Gene Mutation
Time Frame: 07/29/2010-09/30/2010
DNA was extracted from tumor specimens.Screened for the presence of KRAS codon 12 and 13 mutations using a PCR clamping and melting curve technique. PCR amplification of the wild-type KRAS sequence was suppressed in this process by the incorporation in the reaction mix of a locked nucleic-acid oligomer16 spanning codons 12 and 13 of the KRAS gene. Post-PCR hybridization and melting curve analysis using fluorescently tagged oligonucleotides incorporated in the original PCR reaction permitted the identification and discrimination of distinct KRAS codon 12 and 13 missense mutations.
07/29/2010-09/30/2010

Collaborators and Investigators

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

Sponsor

Shandong Cancer Hospital and Institute

Collaborators

Cancer Institute and Hospital, Chinese Academy of Medical Sciences
RenJi Hospital
West China Hospital
Peking University Cancer Hospital & Institute
Jiangsu Cancer Institute & Hospital
Hebei Fourth Hospital
The Affiliated Cancer Hospital of Zhengzhou University

Investigators

  • Study Chair: Jin Ming Yu, PH.D, M.D, Shandong Cancer Hospital and Institute

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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

January 1, 2009

Primary Completion (Actual)

July 1, 2010

Study Completion (Actual)

July 1, 2010

Study Registration Dates

First Submitted

December 29, 2008

First Submitted That Met QC Criteria

December 29, 2008

First Posted (Estimate)

December 30, 2008

Study Record Updates

Last Update Posted (Estimate)

February 8, 2011

Last Update Submitted That Met QC Criteria

February 4, 2011

Last Verified

July 1, 2009

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • SDRTC-0901

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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