Definitive Radiochemotherapy Plus/Minus Cetuximab in Unresectable Locally Advanced Esophageal Cancer
Condition: Esophageal Cancer
MeSH terms: Esophageal Neoplasms
Intervention: Cetuximab; Cisplatin, 5-FU; Radiotherapy
Intervention description: Initial doses 400mg/m2 (day 1), followed by weekly doses of 250mg/m2 for 14 weeks in total; 5-FU: 1000mg/m2 per day as continuous infusion on day 1-4 of cycle 1 and 2, 750mg/m2/day as continuous infusion on day 1-4 of cycle 3 and 4
Cisplatin 20mg/m2/day as intravenous bolus over 60 min on day 1-4 of every cycle; 59.4 Gy (33 fractions of 1.8 Gy) over 6.5-7 weeks (5 x 1.8 Gy per week)on primary tumor. 50.4 Gy on locoregional lymphnodes. If resectability is reached after 4-4.5 weeks (36-41.4 Gy) the radiotherapy stops after 45 Gy and the patient undergoes surgery.
Intervention MeSH terms: Fluorouracil; Cetuximab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 74.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: non resectable; locally advanced; Cetuximab; radiation

Summary:

      Esophageal cancer is a highly aggressive tumor. Treatment options are various and range from
      chemotherapy to radiotherapy and several surgical techniques. Nevertheless, the overall
      survival rates for this disease remain poor.

      During the last years the combination of cetuximab with standard chemotherapy or radiotherapy
      has mainly be investigated in clinical trials focusing on colorectal and/or head and neck
      cancer.

      The results obtained from theses studies were very encouraging and led to the initiation of
      active clinical research in esophageal cancer patients with antibody inhibition of the
      epidermal growth factor receptor (EGFR).

      The first data in this indication are encouraging showing that cetuximab can safely be added
      to chemoradiation for esophageal cancer patients with first hints of efficacy.

      Based on the experiences with cetuximab in colorectal cancer and in combination with
      radiotherapy in head and neck cancer, the aim of the present study is to evaluate the
      feasibility of a combined treatment of cetuximab with continuous infusional 5-FU, cisplatin
      and radiotherapy in patients with esophageal cancer and to assess if the overall survival
      rates can be increased by addition of an EGFR-targeted therapy.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Dated and signed written informed consent

          -  Male or female patients between 18 years and 75 years; patients > 75 years if their
             karnofsky performance status is ≥ 80.

          -  Histologically proven squamous cell carcinoma or adenocarcinoma of the esophagus which
             is not curatively resectable. Resectability has to be defined by a surgeon before
             radiochemotherapy. The tumor is considered unresectable due to T-stage, N-stage,
             performance status, nutritional status, co-morbidity (pulmonal function, other), tumor
             location upper third or other reasons

          -  Karnofsky Performance Status ≥ 70

          -  Women of child-bearing potential must have a negative pregnancy test

          -  Adequate cardial-, pulmonal- and ear function

        Adequate bone marrow function:

          -  leukocytes ≥ 3.0 x 10^9/L

          -  neutrophiles ≥ 1.5 x 10^9/L

          -  thrombocytes ≥ 100 x 10^9/L

          -  hemoglobin ≥ 10.0 g/dl

        Adequate liver function:

          -  bilirubin ≤ 2.0 mg/dl

          -  transaminases (serum glutamic pyruvic transaminase (SGPT), serum glutamic oxaloacetic
             transaminase (SGOT), gamma-GT) ≤ 3 x upper limit of normal (ULN)

        Adequate kidney function:

          -  serum creatinine ≤ 1.5 mg/dl

          -  creatinine clearance ≥ 50 ml/min according to Cockcroft-Gault Formula

          -  no known allergies against chimeric antibodies

          -  effective contraception for male and female patients if there is a risk of conception

        Exclusion Criteria:

          -  distant metastasis

          -  previous treatment of esophageal cancer

          -  previous therapy with monoclonal antibodies and / or EGFR-targeted therapy

          -  previous second malignancies with exception of a history of a previous curatively
             treated basal cell carcinoma of the skin or pre-invasive cervix carcinoma

          -  serious concomitant disease or medical condition

          -  lung function: forced expiratory volume in one second (FEV1)) < 1.1

          -  clinically relevant coronary artery diseases or known myocardial infarction within the
             last 12 months or ventricular ejection fraction (LVEF) below normal

          -  every active dermatological condition > grade 1

          -  contraindications to receive cisplatin, 5-FU or cetuximab

          -  concurrent treatment with other experimental drugs or participation in another
             clinical trial within 30 days before study start

          -  patient pregnant or breast feeding

          -  known drug abuse, medication abuse, alcohol abuse

          -  social situations limiting the compliance with the study requirements