Denne side blev automatisk oversat, og nøjagtigheden af ​​oversættelsen er ikke garanteret. Der henvises til engelsk version for en kildetekst.

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

17. december 2015 opdateret af: UNICANCER

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.

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.

Studieoversigt

Status

Afsluttet

Betingelser

Intervention / Behandling

Detaljeret beskrivelse

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.

Undersøgelsestype

Interventionel

Tilmelding (Faktiske)

266

Fase

  • Fase 2
  • Fase 3

Kontakter og lokationer

Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.

Studiesteder

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

Deltagelseskriterier

Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.

Berettigelseskriterier

Aldre berettiget til at studere

18 år og ældre (Voksen, Ældre voksen)

Tager imod sunde frivillige

Ingen

Køn, der er berettiget til at studere

Alle

Beskrivelse

DISEASE CHARACTERISTICS:

  • 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

PATIENT CHARACTERISTICS:

  • 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

PRIOR CONCURRENT THERAPY:

  • 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

Studieplan

Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.

Hvordan er undersøgelsen tilrettelagt?

Design detaljer

  • Primært formål: Behandling
  • Tildeling: Randomiseret
  • Interventionel model: Parallel tildeling
  • Maskning: Ingen (Åben etiket)

Våben og indgreb

Deltagergruppe / Arm
Intervention / Behandling
Eksperimentel: 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
Stråling: strålebehandling
Medicin: oxaliplatin
Medicin: 5-FU
Andre navne:
  • 5-Fluorouracil
Medicin: Folinsyre
Eksperimentel: 5-FU / cisplatin and radiotherapy
5-FU (100mg/m2); Cisplatin (75mg/m2)
Stråling: strålebehandling
Medicin: cisplatin
Medicin: 5-FU
Andre navne:
  • 5-Fluorouracil

Hvad måler undersøgelsen?

Primære resultatmål

Resultatmål
Tidsramme
Percentage of patients who complete the full study treatment (Phase II)
Tidsramme: 12 weeks
12 weeks
Endoscopic complete response rate (Phase II)
Tidsramme: 12 weeks
12 weeks
Progression-free survival (Phase III)
Tidsramme: Until progression
Until progression

Sekundære resultatmål

Resultatmål
Tidsramme
Safety profile as assessed by NCI CTC v2.0 (Phase II)
Tidsramme: Total duration of the trial
Total duration of the trial
Overall survival (Phase III)
Tidsramme: Total duration of the trial
Total duration of the trial
Complete response rate (Phase III)
Tidsramme: Total duration of the trial
Total duration of the trial
Time to treatment failure (Phase III)
Tidsramme: Total duration of the trial
Total duration of the trial
Incidence of grade 3-4 toxicities (Phase III)
Tidsramme: Total duration of the trial
Total duration of the trial
Quality of life as assessed by EORTC QLQ-C30 (version 3) and EORTC QLQ-OES18 (Phase III)
Tidsramme: Total duration of the trial
Total duration of the trial

Samarbejdspartnere og efterforskere

Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.

Sponsor

UNICANCER

Efterforskere

  • Ledende efterforsker: Thierry Conroy, MD, Centre Alexis Vautrin

Publikationer og nyttige links

Den person, der er ansvarlig for at indtaste oplysninger om undersøgelsen, leverer frivilligt disse publikationer. Disse kan handle om alt relateret til undersøgelsen.

Generelle publikationer

Datoer for undersøgelser

Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.

Studer store datoer

Studiestart

1. marts 2008

Primær færdiggørelse (Faktiske)

1. september 2011

Studieafslutning (Faktiske)

1. december 2012

Datoer for studieregistrering

Først indsendt

12. marts 2009

Først indsendt, der opfyldte QC-kriterier

12. marts 2009

Først opslået (Skøn)

13. marts 2009

Opdateringer af undersøgelsesjournaler

Sidste opdatering sendt (Skøn)

18. december 2015

Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier

17. december 2015

Sidst verificeret

1. december 2015

Mere information

Begreber relateret til denne undersøgelse

Nøgleord

Yderligere relevante MeSH-vilkår

Andre undersøgelses-id-numre

  • CDR0000595050
  • FRE-FNCLCC- ACCORD-17-0707
  • EU-20848

Disse oplysninger blev hentet direkte fra webstedet clinicaltrials.gov uden ændringer. Hvis du har nogen anmodninger om at ændre, fjerne eller opdatere dine undersøgelsesoplysninger, bedes du kontakte register@clinicaltrials.gov. Så snart en ændring er implementeret på clinicaltrials.gov, vil denne også blive opdateret automatisk på vores hjemmeside .

Abonner