Radiation Therapy + Combination Chemotherapy as 1st-Line Therapy for Patients With Inoperable Esophageal Cancer
- Conditions
- Esophageal Cancer
- Interventions
- Registration Number
- NCT00861094
- Lead Sponsor
- UNICANCER
- 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.
- Detailed Description
OBJECTIVES:
Primary
* 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)
Secondary
* 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 266
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description FOLFOX and radiotherapy radiation therapy Oxaliplatin (85mg/m2); Folinic Acid (200mg/m2); 5-FU (400mg/m2-Bolus and 1600mg/m2 over 46h)- once every two weeks for six cycles 5-FU / cisplatin and radiotherapy radiation therapy 5-FU (100mg/m2); Cisplatin (75mg/m2) FOLFOX and radiotherapy oxaliplatin Oxaliplatin (85mg/m2); Folinic Acid (200mg/m2); 5-FU (400mg/m2-Bolus and 1600mg/m2 over 46h)- once every two weeks for six cycles FOLFOX and radiotherapy 5-FU Oxaliplatin (85mg/m2); Folinic Acid (200mg/m2); 5-FU (400mg/m2-Bolus and 1600mg/m2 over 46h)- once every two weeks for six cycles FOLFOX and radiotherapy Folinic Acid Oxaliplatin (85mg/m2); Folinic Acid (200mg/m2); 5-FU (400mg/m2-Bolus and 1600mg/m2 over 46h)- once every two weeks for six cycles 5-FU / cisplatin and radiotherapy cisplatin 5-FU (100mg/m2); Cisplatin (75mg/m2) 5-FU / cisplatin and radiotherapy 5-FU 5-FU (100mg/m2); Cisplatin (75mg/m2)
- Primary Outcome Measures
Name Time Method Endoscopic complete response rate (Phase II) 12 weeks Percentage of patients who complete the full study treatment (Phase II) 12 weeks Progression-free survival (Phase III) Until progression
- Secondary Outcome Measures
Name Time Method Overall survival (Phase III) Total duration of the trial Incidence of grade 3-4 toxicities (Phase III) Total duration of the trial Safety profile as assessed by NCI CTC v2.0 (Phase II) Total duration of the trial Complete response rate (Phase III) Total duration of the trial Time to treatment failure (Phase III) Total duration of the trial Quality of life as assessed by EORTC QLQ-C30 (version 3) and EORTC QLQ-OES18 (Phase III) Total duration of the trial
Trial Locations
- Locations (28)
Hopital Du Bocage
🇫🇷Dijon, France
Hopital Ambroise Pare
🇫🇷Boulogne-Billancourt, France
Hopital Saint Andre
🇫🇷Bordeaux, France
CHR de Besancon - Hopital Saint-Jacques
🇫🇷Besancon, France
Centre Regional Francois Baclesse
🇫🇷Caen, France
Institut Bergonie
🇫🇷Bordeaux, France
Hopital Saint-Louis
🇫🇷Paris, France
Institut Claudius Regaud
🇫🇷Toulouse, France
CHU de la Timone
🇫🇷Marseille, France
Centre Regional de Lutte Contre le Cancer - Centre Val d'Aurelle
🇫🇷Montpellier, France
Hopital Europeen Georges Pompidou
🇫🇷Paris, France
CHU - Robert Debre
🇫🇷Reims, France
Polyclinique Du Parc
🇫🇷Caen, France
Centre de Lutte Contre le Cancer Georges-Francois Leclerc
🇫🇷Dijon, France
Centre Oscar Lambret
🇫🇷Lille, France
Centre Antoine Lacassagne
🇫🇷Nice, France
Hopital Tenon
🇫🇷Paris, France
Centre Eugene Marquis
🇫🇷Rennes, France
Institut Jean Godinot
🇫🇷Reims, France
CHU Poitiers
🇫🇷Poitiers, France
Hopital Charles Nicolle
🇫🇷Rouen, France
Clinique Armoricaine De Radiologie
🇫🇷Saint Brieuc, France
Centre Paul Strauss
🇫🇷Strasbourg, France
Centre Alexis Vautrin
🇫🇷Vandoeuvre-les-Nancy, France
Clinique Du Parc
🇫🇷Toulouse, France
Institut Gustave Roussy
🇫🇷Villejuif, France
Centre Hospital Regional Universitaire de Limoges
🇫🇷Limoges, France
Centre Leon Berard
🇫🇷Lyon, France