A Study to Evaluate the Combination of Cetuximab and Chemotherapy as Neoadjuvant Therapy Followed Concomitant Chemoradiotherapy Plus Cetuximab in Locoregional Esophageal Carcinoma

NCT ID: NCT00733889

Last Updated: 2013-02-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-12-31
• Study Completion Date: 2012-11-30

Brief Summary

The purpose of the study is to determine efficacy ans safety of the combination of cetuximab and chemotherapy (docetaxel, cisplatin, 5-fluorouracil) as neoadjuvant therapy followed concomitant chemoradiotherapy (cisplatin) plus cetuximab in patients with a locoregional esophageal carcinoma

Conditions

Esophageal Carcinoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

1

Group Type: EXPERIMENTAL

cetuximab and chemotherapy (docetaxel, cisplatin, 5-fluorouracil)

Intervention Type: DRUG

Neoadjuvant chemotherapy plus cetuximab:

3 cycles of chemotherapy (Docetaxel: 75 mg/m2; day1; Cisplatin :75 mg/m2, day 1; 5-FU: 750 mg/m2; 24-hour infusion; day1-5) administered every 3 weeks, plus cetuximab (250 mg/m2; day 1, 8 and 15) Cetuximab will be maintained from the beginning of chemotherapy until the end of radiotherapy.

Radio-chemotherapy plus cetuximab:

The radiotherapy treatment: A dose of 50.4 Gy will be administered in 28 fractions of 1.8 Gy / day, 5 days a week (a total of 5.6 weeks).

Cetuximab:250 mg/m2 and Cisplatin: 40 mg/m2, day 1, 8, 15, 22, 29 and 36

Interventions

cetuximab and chemotherapy (docetaxel, cisplatin, 5-fluorouracil)

Neoadjuvant chemotherapy plus cetuximab:

3 cycles of chemotherapy (Docetaxel: 75 mg/m2; day1; Cisplatin :75 mg/m2, day 1; 5-FU: 750 mg/m2; 24-hour infusion; day1-5) administered every 3 weeks, plus cetuximab (250 mg/m2; day 1, 8 and 15) Cetuximab will be maintained from the beginning of chemotherapy until the end of radiotherapy.

Radio-chemotherapy plus cetuximab:

The radiotherapy treatment: A dose of 50.4 Gy will be administered in 28 fractions of 1.8 Gy / day, 5 days a week (a total of 5.6 weeks).

Cetuximab:250 mg/m2 and Cisplatin: 40 mg/m2, day 1, 8, 15, 22, 29 and 36

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Informed consent form signed before performing any of the study's specific procedures.
• Age > 18 and < 70.
• Karnofsky performance status > 70% upon inclusion in the study.
• Life expectancy of more than 3 months.
• Histologically confirmed diagnosis of squamous cell carcinoma or adenocarcinoma of the oesophagus or the gastroesophageal junction. The disease must be confined to the oesophagus or gastroesophageal junction and the perioesophageal region. There must be no tumor extension beyond 2 cm into the stomach.
• Stages II or III. The patients must have a T1N1M0 or T2-4; any N; M0. The only exception would be patients with stage IVA: an oesophageal carcinoma of the upper thoracic region with metastasis in cervical lymph nodes (M1a) and an oesophageal carcinoma of the lower thoracic region with metastasis in the celiac lymph nodes (M1a), providing the disease remains within the radiotherapy fields.
• Presence of a unidimensionally measurable and/or assessable lesion
• Neutrophils >1500/mm3, platelet count >150,000/mm3 and haemoglobin >10 g/dl.
• Adequate renal function: serum creatinine < 120 micromol/l (1.4 mg/dl); if the values are >120 micromol/l (1.4 mg/dl) creatinine clearance must be > 65 ml/min.
• Adequate liver function: total bilirubin <1 x NUL; aspartate aminotransferase (AST) and alanine aminotransferase (ALT) <2.5 x NUL; alkaline phosphatase (AP) < 5 x NUL. Patients with AST and/or ALT > 1.5 < 2.5 x NUL and AP > 1.5 x NUL < 5 x NUL are not eligible.
• Serum calcium <1.25 x normal upper limit (NUL).
• Adequate nutritional status: weight loss < 20% of regular weight and albumin > 35 g/l.
• Total oral and/or enteral intake should be at least 1700 calories/day.
• Use of an effective contraceptive method for patients of both sexes when there is a risk of conception and/or pregnancy.
• Availability of tumour tissue for immunohistochemical analysis of EGFR expression and other biological markers.

Exclusion Criteria

• Patients with a tracheo-oesophageal fistula or direct invasion of the tracheal mucosa or a major bronchi are not eligible. Bronchoscopy (with biopsy and cytology if lesion is seen) is required in order to rule out a fistula and/or direct invasion if the primary tumour is < than 30 cm from the incisors. Bronchoscopy is also required when the primary tumour is shown to be at or above the carina by an imaging study.
• Prior thoracic radiotherapy and/or systemic chemotherapy and/or oesophageal surgery.
• Patients with multiple carcinoma of the oesophagus.
• Diagnosis of any other cancer in the previous 5 years with the exception of appropriately treated carcinoma in situ of the uterine cervix and/or basal cell carcinoma of the skin.
• Systemic, chronic and concomitant immune treatment, or anti-cancer hormone therapy.
• Other concomitant cancer treatments.
• Active infection (infection requiring intravenous antibiotics), including active tuberculosis and diagnosed HIV.
• Uncontrolled hypertension defined as systolic blood pressure > 180 mmHg and/or diastolic blood pressure > 130 mmHg at rest.
• Active, uncontrolled, gastric or duodenal peptic ulcer.
• Chronic obstructive pulmonary disease requiring hospitalisation in the 6 months prior to inclusion in the study.
• History of atrioventricular arrhythmia and/or cardiac failure and/or second or third degree heart block.
• Clinically significant coronary artery disease or history of myocardial infarction in the last 12 months .
• Peripheral neuropathy grade > 2 NCIC-CTG of any aetiology.
• Hearing disorder grade > 2 NCIC-CTG of any aetiology.
• Any other disease or medical disorder suggesting that the patient will not be able to complete the study.
• Any psychological disorder suggesting that the complete treatment will not be possible.
• Pregnancy (its absence must be confirmed by the serum HCG-betatest) or lactation.
• Known drug abuse (with the exception of the mild or moderate consumption of alcohol upon inclusion in the study).
• Known allergic reaction to any of the components in the study treatment.
• Prior treatment with monoclonal antibodies or other signal transduction inhibitors or EGFR-targeted treatment.
• Evidence of another cancer, with the exception of a carcinoma in situ of the uterine cervix and/or a basal cell carcinoma of the skin.
• Any experimental treatment in the 30 days prior to inclusion in the study.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: collaborator

Sanofi

INDUSTRY

Sponsor Role: collaborator

Spanish Cooperative Group for the Treatment of Digestive Tumours (TTD)

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Josep Tabernero, MD; phD

Role: STUDY_CHAIR

Medical Oncology Department; Hospital Universitario Vall d'Hebrón; Barcelona

Jordi Giralt, MD; phD

Role: STUDY_CHAIR

Oncology Radiation Department; Hospital Universitario Vall d'Hebrón; Barcelona

Locations

Spanish Cooperative Group for Gastrointestinal Tumour Therapy

Madrid, , Spain

Countries

Spain

References

Alsina M, Rivera F, Ramos FJ, Galan M, Lopez R, Garcia-Alfonso P, Ales-Martinez JE, Queralt B, Anton A, Carrato A, Gravalos C, Mendez-Vidal MJ, Lopez C, de Mena IR, Tabernero J, Giralt J, Aranda E; Spanish Cooperative Group for the Treatment of Digestive Tumors (TTD) and Grupo de Investigacion Clinica en Oncologia Radioterapica (GICOR). A phase II Study Evaluating Combined Neoadjuvant Cetuximab and Chemotherapy Followed by Chemoradiotherapy and Concomitant Cetuximab in Locoregional Oesophageal Cancer Patients. Target Oncol. 2018 Feb;13(1):69-78. doi: 10.1007/s11523-017-0536-z.

Reference Type: DERIVED

PMID: 29128908 (View on PubMed)

Other Identifiers

EudraCT number:2006-001880-42

Identifier Type: -

Identifier Source: secondary_id

TTD-06-02

Identifier Type: -

Identifier Source: org_study_id