Study Comparing Radiochemotherapy With Folfox 4 Regimen or 5FU-Cisplatin in Patients With Inoperable Esophageal Cancer

Phase II Study Comparing Radiochemotherapy With the Folfox 4 Regimen Versus Radiochemotherapy With 5FU-Cisplatin (Herskovic Regimen) in First Line Treatment of Patients With Inoperable Esophageal Cancer

The primary objectives of this study are to assess the feasibility (completion of full treatment) in both arms and to assess endoscopic complete response rate in both arms.

The secondary objective of this study is to assess the toxicity profile of each arm using the National Cancer Institute-Common Toxicity Criteria (NCI-CTC) scale (V.3).

Study Overview

• Status: Completed
• Conditions: Esophageal Neoplasms
• Intervention / Treatment: Drug: FOLFOX 4; Drug: 5-FU / Cisplatin

• Study Type: Interventional
• Enrollment (Actual): 97
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Paris, France
    • Sanofi-Aventis

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Patients with:

• Histologically proven adenocarcinoma, squamous cell or adenosquamous carcinoma of the esophagus
• Inoperable esophageal carcinoma (disease status: any T, N0 or N1, M0 or M1a) or surgical contraindication conditions
• No prior treatment for esophageal cancer (surgery, laser, chemo- or radiotherapy)
• Oesophageal dilatation is allowed before or during the treatment, but prior esophageal prosthesis is not allowed
• Peripheral neuropathy <= NCI-CTC grade 1
• Age >= 18 years
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) <= 2
• Sufficient (oral or with gastrostomy) calorific intake (> 1000 Kcal/m2/day)
• Life expectancy >= 3 months

• Adequate bone marrow reserve, normal renal and liver functions:

  • Neutrophil count >= 1500/mm³
  • Platelet count >= 100,000/mm³
  • Hemoglobin >= 10 g/dl (after transfusion, if necessary)
  • Creatinine levels <= 1.5 x the upper normal limit of institutional values (ULN)
  • Total bilirubin level < 1.5 x ULN
  • ALT/AST < 2.5 x ULN
  • Prothrombin time >= 60%
• Laboratory values obtained the week preceding study entry
• Signed informed consent (prior to all study procedures)
• Start of treatment within 28 days of inclusion.

Exclusion Criteria:

• Metastatic disease except for third upper or cervical esophagus tumor with regional nodes, or third lower esophagus tumor with celiac nodes (M1a)
• Multiple carcinomas of the esophagus
• Small cell or undifferentiated carcinoma of the esophagus
• Complete dysphagia (grade 4 NCI-CTC); patient with exclusive parenteral nutrition.
• Weight loss > 20% normal body weight
• Pregnant or breast-feeding women
• Fertile patient not using adequate contraception
• Peripheral sensitive neuropathy with functional impairment
• Auditory disorders
• History of prior malignancies (other than cured non melanoma skin cancer, cured cervical carcinoma in situ or stage I or II node negative head and neck cancer cured > 3 years ago)
• Prior cervical, thoracic and abdominal radiotherapy with field overlapping the proposed oesophageal radiotherapy field
• Tracheo-oesophageal fistula or invasion of the tracheo-bronchial tree
• Previous myocardial infarction (inferior or equal to 6 months). Patients with a previous myocardial infarction superior to 6 months, could be included only if: no transient ischemia is shown by thallium myocardial scintigraphy and favourable advice for chemotherapy is obtained from a cardiologist.
• Other serious illness or medical conditions (such as symptomatic coronary disease, left ventricular failure or uncontrolled infection)
• Arterial disease stage II to IV according to the Leriche and Fontaine classification
• Treatment with any other experimental drugs or participation in another clinical trial within 30 days of study screening
• Concurrent treatment with any other anti-cancer therapy
• Concurrent treatment with phenytoin and yellow fever vaccine; geographical, social or psychological circumstances preventing regular follow-up.

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1	Drug: FOLFOX 4; total treatment of six 2-weekly cycles of FOLFOX 4, the first 3 cycles starting on D1, D15 and D29 concomitant with 5 weeks' radiotherapy.
Active Comparator: 2	Drug: 5-FU / Cisplatin; two cycles of 5-FU / Cisplatin on week 1 and 5 of radiotherapy and two cycles of chemotherapy with 5-FU / Cisplatin on week 8 and 11 (one cycle each three weeks after the end of radiotherapy).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Percentage of patients having completed the full treatment and Endoscopic complete response rate	at the end of the study

Secondary Outcome Measures

Outcome Measure	Time Frame
Toxicity profile (NCI-CTC).	evaluated each week

Collaborators and Investigators

• Sponsor: Sanofi
• Investigators: Study Director: Marie SEBILLE, Sanofi

Study record dates

Study Major Dates

• Study Start: September 1, 2004
• Primary Completion (Actual): October 1, 2007

Study Registration Dates

• First Submitted: September 9, 2005
• First Submitted That Met QC Criteria: September 9, 2005
• First Posted (Estimate): September 12, 2005

Study Record Updates

• Last Update Posted (Estimate): December 7, 2009
• Last Update Submitted That Met QC Criteria: December 4, 2009
• Last Verified: December 1, 2009

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Head and Neck Neoplasms; Esophageal Diseases; Esophageal Neoplasms; Antineoplastic Agents; Cisplatin
• Other Study ID Numbers: L_9326