Clinical trial NCT00815308: Erbitux Combined With Chemo-radiotherapy in Esophageal Squamous Cell Carcinoma
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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Esophageal Cancer
Keywords: Therapeutic
Drug Therapy, combination
Radiotherapy
Lead sponsor: Shandong Cancer Hospital and Institute
Sponsor class: OTHER
Collaborators: name: Chinese Academy of Medical Sciences
name: Peking University Cancer Hospital & Institute
name: Hebei Fourth Hospital
name: Jiangsu Cancer Institute & Hospital
name: RenJi Hospital
name: The Affiliated Cancer Hospital of Zhengzhou University
name: West China Hospital
First posted: 2008-12-30
Enrollment: 55
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Number of Participants With Overall Response Rate (RR)
timeFrame: 1 to 3 month after therapy
Secondary outcomes:
measure: Number of Participants With Toxicity
timeFrame: Every week during treatment and 1 month after therapy
measure: Participants With Overall Survival (OS) at 1 Year
timeFrame: 1 year from the date of diagnosis
measure: Participants With Overall Survival (OS) at 3 Year
timeFrame: 3 year from the date of diagnosis
measure: Participants With Progression Free Survival (PFS)
timeFrame: Recurrence or metastasis from the date of diagnosis
measure: Number of Participants With K-ras Gene Mutation
timeFrame: 07/29/2010-09/30/2010
Other outcomes:
Locations:
city: Jinan
country: China
facility: Department of Radiation Oncology, Shandong Cancer Hospital and Institute
state: Shandong
Study officials:
affiliation: Shandong Cancer Hospital and Institute
name: Jin Ming Yu, PH.D, M.D
role: STUDY_CHAIR
References:
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citation: Bonner JA, Harari PM, Giralt J, Azarnia N, Shin DM, Cohen RB, Jones CU, Sur R, Raben D, Jassem J, Ove R, Kies MS, Baselga J, Youssoufian H, Amellal N, Rowinsky EK, Ang KK. Radiotherapy plus cetuximab for squamous-cell carcinoma of the head and neck. N Engl J Med. 2006 Feb 9;354(6):567-78. doi: 10.1056/NEJMoa053422.