Erbitux Combined With Chemo-radiotherapy in Esophageal Squamous Cell Carcinoma (EXCEL)
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.
Drug: cetuximab (Erbitux)
|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)|
- 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.
- 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.
|Study Start Date:||January 2009|
|Study Completion Date:||July 2010|
|Primary Completion Date:||July 2010 (Final data collection date for primary outcome measure)|
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: erbituxDrug: 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).
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.
|Department of Radiation Oncology, Shandong Cancer Hospital and Institute|
|Jinan, Shandong, China, 250117|
|Study Chair:||Jin Ming Yu, PH.D, M.D||Shandong Cancer Hospital and Institute|