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

This study has been completed.
Sponsor:
Collaborators:
Chinese Academy of Medical Sciences
Beijing Cancer Hospital
Hebei Fourth Hospital
Jiangsu Cancer Institute & Hospital
RenJi Hospital
The Affiliated Cancer Hospital of Zhengzhou University
West China Hospital
Information provided by:
Shandong Cancer Hospital and Institute
ClinicalTrials.gov Identifier:
NCT00815308
First received: December 29, 2008
Last updated: February 4, 2011
Last verified: July 2009
  Purpose

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.


Condition Intervention Phase
Esophageal Cancer
Drug: cetuximab (Erbitux)
Drug: Paclitaxel
Drug: Cisplatin
Radiation: Radiation
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open-labeled Study to Evaluate Efficacy of Combining Erbitux Plus Concurrent Chemo-radiotherapy in Locally Advanced Esophageal Squamous Cell Carcinoma (ESCC)

Resource links provided by NLM:


Further study details as provided by Shandong Cancer Hospital and Institute:

Primary Outcome Measures:
  • Number of Participants With Overall Response Rate (RR) [ Time Frame: 1 to 3 month after therapy ] [ Designated as safety issue: Yes ]
    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.


Secondary Outcome Measures:
  • Number of Participants With Toxicity [ Time Frame: Every week during treatment and 1 month after therapy ] [ Designated as safety issue: Yes ]
    All patients were regularly monitored for possible adverse events, which were graded according to National Cancer Institute Common Toxicity Criteria version 3.0.

  • Participants With Overall Survival (OS) at 1 Year [ Time Frame: 1 year from the date of diagnosis ] [ Designated as safety issue: No ]
  • Participants With Overall Survival (OS) at 3 Year [ Time Frame: 3 year from the date of diagnosis ] [ Designated as safety issue: No ]
  • Participants With Progression Free Survival (PFS) [ Time Frame: Recurrence or metastasis from the date of diagnosis ] [ Designated as safety issue: No ]
  • Number of Participants With K-ras Gene Mutation [ Time Frame: 07/29/2010-09/30/2010 ] [ Designated as safety issue: No ]
    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.


Enrollment: 55
Study Start Date: January 2009
Study Completion Date: July 2010
Primary Completion Date: July 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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

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.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00815308

Locations
China, Shandong
Department of Radiation Oncology, Shandong Cancer Hospital and Institute
Jinan, Shandong, China, 250117
Sponsors and Collaborators
Shandong Cancer Hospital and Institute
Chinese Academy of Medical Sciences
Beijing Cancer Hospital
Hebei Fourth Hospital
Jiangsu Cancer Institute & Hospital
RenJi Hospital
The Affiliated Cancer Hospital of Zhengzhou University
West China Hospital
Investigators
Study Chair: Jin Ming Yu, PH.D, M.D Shandong Cancer Hospital and Institute
  More Information

Publications:

Responsible Party: Jinming Yu, Shandong Cancer Hospital and Institute
ClinicalTrials.gov Identifier: NCT00815308     History of Changes
Other Study ID Numbers: SDRTC-0901
Study First Received: December 29, 2008
Results First Received: October 15, 2010
Last Updated: February 4, 2011
Health Authority: China: Ethics Committee
China: Food and Drug Administration

Keywords provided by Shandong Cancer Hospital and Institute:
Therapeutic
Drug Therapy, combination
Radiotherapy

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Squamous Cell
Esophageal Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Squamous Cell
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Head and Neck Neoplasms
Digestive System Diseases
Esophageal Diseases
Gastrointestinal Diseases
Cetuximab
Cisplatin
Paclitaxel
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Antineoplastic Agents, Phytogenic
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 19, 2014