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

Primary Purpose

Esophageal Cancer

Status
Completed
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
cetuximab (Erbitux)
Paclitaxel
Cisplatin
Radiation
Sponsored by
Shandong Cancer Hospital and Institute
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Esophageal Cancer focused on measuring Therapeutic, Drug Therapy, combination, Radiotherapy

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Department of Radiation Oncology, Shandong Cancer Hospital and Institute

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

cetuximab, concurrent chemo-radiotherapy

Arm Description

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

Outcomes

Primary Outcome Measures

Number of Participants With Overall Response Rate (RR)
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
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
Participants With Overall Survival (OS) at 3 Year
Participants With Progression Free Survival (PFS)
Number of Participants With K-ras Gene Mutation
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.

Full Information

First Posted
December 29, 2008
Last Updated
February 4, 2011
Sponsor
Shandong Cancer Hospital and Institute
Collaborators
Chinese Academy of Medical Sciences, Peking University Cancer Hospital & Institute, Hebei Fourth Hospital, Jiangsu Cancer Institute & Hospital, RenJi Hospital, The Affiliated Cancer Hospital of Zhengzhou University, West China Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT00815308
Brief Title
Erbitux Combined With Chemo-radiotherapy in Esophageal Squamous Cell Carcinoma
Acronym
EXCEL
Official Title
An Open-labeled Study to Evaluate Efficacy of Combining Erbitux Plus Concurrent Chemo-radiotherapy in Locally Advanced Esophageal Squamous Cell Carcinoma (ESCC)
Study Type
Interventional

2. Study Status

Record Verification Date
July 2009
Overall Recruitment Status
Completed
Study Start Date
January 2009 (undefined)
Primary Completion Date
July 2010 (Actual)
Study Completion Date
July 2010 (Actual)

3. Sponsor/Collaborators

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

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Esophageal Cancer
Keywords
Therapeutic, Drug Therapy, combination, Radiotherapy

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
55 (Actual)

8. Arms, Groups, and Interventions

Arm Title
cetuximab, concurrent chemo-radiotherapy
Arm Type
Experimental
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
cetuximab (Erbitux)
Other Intervention Name(s)
erbitux
Intervention Description
Cetuximab,injection,loading dose400 mg/m^2,(Day1 in Week1) followed by 250 mg/m^2(Day1, every week for Weeks 2-8)
Intervention Type
Drug
Intervention Name(s)
Paclitaxel
Intervention Description
Paclitaxel,injection,loading dose 45 mg/m^2,(Day1 in every week for Weeks 2-8)
Intervention Type
Drug
Intervention Name(s)
Cisplatin
Intervention Description
Cisplatin,injection,loading dose 20 mg/m^2,(Day1 in every week for Weeks 2-8)
Intervention Type
Radiation
Intervention Name(s)
Radiation
Other Intervention Name(s)
Conformal Radiotherapy, Intensity Modulated Radiotherapy
Intervention Description
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).
Primary Outcome Measure Information:
Title
Number of Participants With Overall Response Rate (RR)
Description
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.
Time Frame
1 to 3 month after therapy
Secondary Outcome Measure Information:
Title
Number of Participants With Toxicity
Description
All patients were regularly monitored for possible adverse events, which were graded according to National Cancer Institute Common Toxicity Criteria version 3.0.
Time Frame
Every week during treatment and 1 month after therapy
Title
Participants With Overall Survival (OS) at 1 Year
Time Frame
1 year from the date of diagnosis
Title
Participants With Overall Survival (OS) at 3 Year
Time Frame
3 year from the date of diagnosis
Title
Participants With Progression Free Survival (PFS)
Time Frame
Recurrence or metastasis from the date of diagnosis
Title
Number of Participants With K-ras Gene Mutation
Description
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.
Time Frame
07/29/2010-09/30/2010

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jin Ming Yu, PH.D, M.D
Organizational Affiliation
Shandong Cancer Hospital and Institute
Official's Role
Study Chair
Facility Information:
Facility Name
Department of Radiation Oncology, Shandong Cancer Hospital and Institute
City
Jinan
State/Province
Shandong
ZIP/Postal Code
250117
Country
China

12. IPD Sharing Statement

Citations:
PubMed Identifier
11208820
Citation
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Results Reference
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PubMed Identifier
9869669
Citation
Kelsen DP, Ginsberg R, Pajak TF, Sheahan DG, Gunderson L, Mortimer J, Estes N, Haller DG, Ajani J, Kocha W, Minsky BD, Roth JA. Chemotherapy followed by surgery compared with surgery alone for localized esophageal cancer. N Engl J Med. 1998 Dec 31;339(27):1979-84. doi: 10.1056/NEJM199812313392704.
Results Reference
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PubMed Identifier
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Citation
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PubMed Identifier
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Citation
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Results Reference
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PubMed Identifier
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Citation
Herskovic A, Martz K, al-Sarraf M, Leichman L, Brindle J, Vaitkevicius V, Cooper J, Byhardt R, Davis L, Emami B. Combined chemotherapy and radiotherapy compared with radiotherapy alone in patients with cancer of the esophagus. N Engl J Med. 1992 Jun 11;326(24):1593-8. doi: 10.1056/NEJM199206113262403.
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Raben D, Helfrich B, Bunn PA Jr. Targeted therapies for non-small-cell lung cancer: biology, rationale, and preclinical results from a radiation oncology perspective. Int J Radiat Oncol Biol Phys. 2004;59(2 Suppl):27-38. doi: 10.1016/j.ijrobp.2004.01.054.
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Results Reference
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Erbitux Combined With Chemo-radiotherapy in Esophageal Squamous Cell Carcinoma

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