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

Shandong First Medical University

Status and phase: Completed; Phase 2

Conditions: Esophageal Cancer

Treatments: Radiation: Radiation; Drug: Cisplatin; Drug: cetuximab (Erbitux); Drug: Paclitaxel

Study type: Interventional

Funder types: Other

Identifiers

NCT00815308

SDRTC-0901

Details and patient eligibility

About

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.

Full 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.

Enrollment: 55 patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No 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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

---

55 participants in 1 patient group

cetuximab, concurrent chemo-radiotherapy

Experimental group

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

Treatment:

Drug: Cisplatin

Drug: Paclitaxel

Radiation: Radiation

Drug: cetuximab (Erbitux)