Radiation Therapy + Combination Chemotherapy as 1st-Line Therapy for Patients With Inoperable Esophageal Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00861094
Recruitment Status : Completed
First Posted : March 13, 2009
Last Update Posted : December 18, 2015
Information provided by (Responsible Party):

Brief Summary:

RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells. Drugs used in chemotherapy, such as oxaliplatin, fluorouracil, leucovorin, and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) together with radiation therapy may kill more tumor cells.

PURPOSE: This randomized phase II/III trial is studying radiation therapy and two different combination chemotherapy regimens to compare how well they work as first-line therapy in treating patients with esophageal cancer that cannot be removed by surgery.

Condition or disease Intervention/treatment Phase
Esophageal Cancer Drug: cisplatin Drug: 5-FU Drug: oxaliplatin Radiation: radiation therapy Drug: Folinic Acid Phase 2 Phase 3

Detailed Description:



  • To assess the feasibility of radiochemotherapy comprising oxaliplatin, fluorouracil, and leucovorin calcium (FOLFOX regimen) vs fluorouracil and cisplatin (Herskovic regimen) in patients with inoperable esophageal cancer. (Phase II)
  • To assess the endoscopic complete response rate in patients treated with these regimens. (Phase II)
  • To compare the event-free survival of patients treated with these regimens. (Phase III)


  • To assess the toxicity profile of these regimens using the NCI CTC v2.0 criteria. (Phase II)
  • To compare the overall survival, endoscopic complete response rate, incidence of grade 3-4 toxicities, and time to treatment failure in patients treated with these regimens. (Phase III)
  • To evaluate the quality of life of these patients using EORTC QLQ-C30 (version 3) and a validated disease-specific module EORTC QLQ-OES18. (Phase III)

OUTLINE: This is a multicenter study. Patients are stratified according to histological type (adenocarcinoma or adenosquamous carcinoma vs squamous cell carcinoma), pretreatment weight loss within the past 6 months (grade 1 [< 10%] vs grade 2 [≥ 10%]), ECOG performance status (0 vs 1 vs 2), and participating center. Patients are randomized to 1 of 2 treatment arms.

  • Arm I (modified FOLFOX 4 regimen): Patients undergo radiotherapy 5 days a week for 5 weeks. Beginning concurrently with radiotherapy, patients receive oxaliplatin IV over 2 hours and leucovorin calcium IV over 2 hours on day 1 and fluorouracil IV continuously over 46 hours on days 1 and 2. Treatment with chemotherapy repeats every 2 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity.
  • Arm II (Herskovic regimen): Patients undergo radiotherapy as in arm I. Patients also receive cisplatin IV continuously over 24 hours on day 1 and fluorouracil IV continuously over 96 hours on days 1-4 of weeks 1, 5, 8, and 11 in the absence of disease progression or unacceptable toxicity.

Quality of life is assessed at baseline, periodically during study therapy, and then every 6 months for 1 year and annually for 3 years after completion of study therapy.

After completion of study therapy, patients are followed at 4 weeks and then every 3-6 months until disease progression.

PROJECTED ACCRUAL: A total of 97 patients will be accrued for the phase II portion of the study. A total of 169 patients will be accrued for the phase III portion of the study.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 266 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II-III Study Comparing Radiochemotherapy With the FOLFOX Regimen Versus Radiochemotherapy With 5FU-cisplatin (Herskovic Regimen) in First Line Treatment of Patients With Inoperable Oesophageal Cancer.
Study Start Date : March 2008
Actual Primary Completion Date : September 2011
Actual Study Completion Date : December 2012

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: FOLFOX and radiotherapy
Oxaliplatin (85mg/m2); Folinic Acid (200mg/m2); 5-FU (400mg/m2-Bolus and 1600mg/m2 over 46h)- once every two weeks for six cycles
Drug: 5-FU
Other Name: 5-Fluorouracil

Drug: oxaliplatin
Radiation: radiation therapy
Drug: Folinic Acid
Experimental: 5-FU / cisplatin and radiotherapy
5-FU (100mg/m2); Cisplatin (75mg/m2)
Drug: cisplatin
Drug: 5-FU
Other Name: 5-Fluorouracil

Radiation: radiation therapy

Primary Outcome Measures :
  1. Percentage of patients who complete the full study treatment (Phase II) [ Time Frame: 12 weeks ]
  2. Endoscopic complete response rate (Phase II) [ Time Frame: 12 weeks ]
  3. Progression-free survival (Phase III) [ Time Frame: Until progression ]

Secondary Outcome Measures :
  1. Safety profile as assessed by NCI CTC v2.0 (Phase II) [ Time Frame: Total duration of the trial ]
  2. Overall survival (Phase III) [ Time Frame: Total duration of the trial ]
  3. Complete response rate (Phase III) [ Time Frame: Total duration of the trial ]
  4. Time to treatment failure (Phase III) [ Time Frame: Total duration of the trial ]
  5. Incidence of grade 3-4 toxicities (Phase III) [ Time Frame: Total duration of the trial ]
  6. Quality of life as assessed by EORTC QLQ-C30 (version 3) and EORTC QLQ-OES18 (Phase III) [ Time Frame: Total duration of the trial ]

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


  • Histologically proven adenocarcinoma, squamous cell carcinoma, or adenosquamous carcinoma of the esophagus

    • Locally advanced disease (any T, N0 or N1, M0 or M1a)

      • No metastatic disease, except for tumor involvement of the upper third of the esophagus or cervical esophageal tumor with regional nodes, or tumor involvement of the lower third of the esophagus with celiac nodes (M1a)

        • Cervical primary tumor with positive supraclavicular or cervical lymph nodes (defined as N1) allowed
        • No radiographic evidence of enlarged (≥ 1.5 cm) celiac lymph nodes by CT scan or echography
    • No small cell or undifferentiated carcinoma of the esophagus
    • No multiple carcinomas of the esophagus (i.e., > 1 esophageal tumor)
    • No cardia tumor (Siewert II) or gastric tumor extension to the esophagus (Siewert III)

      • Esophageal tumor extension to the cardia (Siewert I) (center of the tumor lying > 1 cm-5 cm above gastroesophageal junction) allowed
  • Inoperable disease OR surgery is contraindicated
  • No tracheo-esophageal fistula or invasion of the tracheo-bronchial tree


  • ECOG performance status 0-2
  • Life expectancy ≥ 3 months
  • Absolute neutrophil count ≥ 1,500/mm³
  • Platelet count ≥ 100,000/mm³
  • Hemoglobin ≥ 10 g/dL (transfusion allowed)
  • Creatinine < 15 mg/L
  • Total bilirubin < 1.5 times upper limit of normal (ULN)
  • ALT and AST < 2.5 times ULN
  • Prothrombin time ≥ 60%
  • Not pregnant or nursing
  • Fertile patients must use effective contraception
  • Caloric intake sufficient (i.e., > 1,000 Kcal/m²/day) (orally or with gastrostomy)
  • No weight loss > 20% normal body weight within the past 3 months
  • No complete dysphagia
  • No exclusive requirement for parenteral nutrition
  • No peripheral neuropathy > grade 1

    • No sensitive peripheral neuropathy with functional impairment
  • No auditory disorders
  • No other prior malignancies except curatively treated nonmelanoma skin cancer or carcinoma in situ of the cervix or stage I or II node-negative head and neck cancer that was curatively treated > 3 years ago
  • No myocardial infarction within the past 6 months

    • Patients who have had a myocardial infarction > 6 months ago are eligible provided there is no transient ischemia by thallium myocardial scintigraphy and patient is able to undergo chemotherapy , as determined by a cardiologist
  • No other serious illness or medical condition (e.g., symptomatic coronary disease, left ventricular failure, or uncontrolled infection)
  • No stage II-IV arterial disease, according to the DE LERICHE and FONTAINE classification
  • No geographical, social, or psychological circumstances preventing regular follow-up


  • No prior treatment for esophageal cancer (e.g., surgery, chemotherapy, or radiotherapy)
  • No prior cervical, thoracic, or abdominal radiotherapy with field overlapping the proposed esophageal radiotherapy field
  • More than 30 days since prior experimental drugs or participation in another clinical trial
  • No other concurrent anticancer therapy
  • No concurrent phenytoin or yellow fever vaccine
  • No concurrent high-dose, long-term corticosteroids
  • No concurrent calcium gluconate/magnesium sulfate infusions
  • No concurrent hematopoietic growth factors
  • No concurrent esophageal dilatation

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00861094

CHR de Besancon - Hopital Saint-Jacques
Besancon, France, 25030
Hopital Saint Andre
Bordeaux, France, 33075
Institut Bergonie
Bordeaux, France, 33076
Hopital Ambroise Pare
Boulogne-Billancourt, France, F-92104
Polyclinique Du Parc
Caen, France, 14052
Centre Regional Francois Baclesse
Caen, France, 14076
Hopital Du Bocage
Dijon, France, 21034
Centre de Lutte Contre le Cancer Georges-Francois Leclerc
Dijon, France, 21079
Centre Oscar Lambret
Lille, France, 59020
Centre Hospital Regional Universitaire de Limoges
Limoges, France, 87042
Centre Leon Berard
Lyon, France, 69373
CHU de la Timone
Marseille, France, 13385
Centre Regional de Lutte Contre le Cancer - Centre Val d'Aurelle
Montpellier, France, 34298
Centre Antoine Lacassagne
Nice, France, 06189
Hopital Europeen Georges Pompidou
Paris, France, 75015
Hopital Saint-Louis
Paris, France, 75475
Hopital Tenon
Paris, France, 75970
CHU Poitiers
Poitiers, France, 86021
Institut Jean Godinot
Reims, France, 51056
CHU - Robert Debre
Reims, France, 51092
Centre Eugene Marquis
Rennes, France, 35042
Hopital Charles Nicolle
Rouen, France, 76031
Clinique Armoricaine De Radiologie
Saint Brieuc, France, F-22015
Centre Paul Strauss
Strasbourg, France, 67065
Institut Claudius Regaud
Toulouse, France, 31052
Clinique Du Parc
Toulouse, France, 31078
Centre Alexis Vautrin
Vandoeuvre-les-Nancy, France, 54511
Institut Gustave Roussy
Villejuif, France, F-94805
Sponsors and Collaborators
Principal Investigator: Thierry Conroy, MD Centre Alexis Vautrin

Publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: UNICANCER Identifier: NCT00861094     History of Changes
Other Study ID Numbers: CDR0000595050
First Posted: March 13, 2009    Key Record Dates
Last Update Posted: December 18, 2015
Last Verified: December 2015

Keywords provided by UNICANCER:
adenocarcinoma of the esophagus
squamous cell carcinoma of the esophagus
stage IIA esophageal cancer
stage IIB esophageal cancer
stage IIIA esophageal cancer
stage IIIB esophageal cancer
stage IIIC esophageal cancer
stage IV esophageal cancer

Additional relevant MeSH terms:
Esophageal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Head and Neck Neoplasms
Digestive System Diseases
Esophageal Diseases
Gastrointestinal Diseases
Folic Acid
Antineoplastic Agents
Protective Agents
Physiological Effects of Drugs
Vitamin B Complex
Growth Substances