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

NCT ID: NCT00861094

Last Updated: 2015-12-18

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2/PHASE3

Total Enrollment

266 participants

Study Classification

INTERVENTIONAL

Study Start Date

2008-03-31

Study Completion Date

2012-12-31

Brief Summary

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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

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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.

Conditions

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Esophageal Cancer

Keywords

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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

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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

Group Type EXPERIMENTAL

5-FU

Intervention Type DRUG

oxaliplatin

Intervention Type DRUG

radiation therapy

Intervention Type RADIATION

Folinic Acid

Intervention Type DRUG

5-FU / cisplatin and radiotherapy

5-FU (100mg/m2); Cisplatin (75mg/m2)

Group Type EXPERIMENTAL

cisplatin

Intervention Type DRUG

5-FU

Intervention Type DRUG

radiation therapy

Intervention Type RADIATION

Interventions

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cisplatin

Intervention Type DRUG

5-FU

Intervention Type DRUG

oxaliplatin

Intervention Type DRUG

radiation therapy

Intervention Type RADIATION

Folinic Acid

Intervention Type DRUG

Other Intervention Names

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5-Fluorouracil

Eligibility Criteria

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Inclusion Criteria

* 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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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UNICANCER

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Thierry Conroy, MD

Role: PRINCIPAL_INVESTIGATOR

Centre Alexis Vautrin

Locations

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CHR de Besancon - Hopital Saint-Jacques

Besançon, , France

Site Status

Hopital Saint Andre

Bordeaux, , France

Site Status

Institut Bergonie

Bordeaux, , France

Site Status

Hopital Ambroise Pare

Boulogne-Billancourt, , France

Site Status

Polyclinique Du Parc

Caen, , France

Site Status

Centre Regional Francois Baclesse

Caen, , France

Site Status

Hopital Du Bocage

Dijon, , France

Site Status

Centre de Lutte Contre le Cancer Georges-Francois Leclerc

Dijon, , France

Site Status

Centre Oscar Lambret

Lille, , France

Site Status

Centre Hospital Regional Universitaire de Limoges

Limoges, , France

Site Status

Centre Leon Berard

Lyon, , France

Site Status

CHU de la Timone

Marseille, , France

Site Status

Centre Regional de Lutte Contre le Cancer - Centre Val d'Aurelle

Montpellier, , France

Site Status

Centre Antoine Lacassagne

Nice, , France

Site Status

Hopital Europeen Georges Pompidou

Paris, , France

Site Status

Hopital Saint-Louis

Paris, , France

Site Status

Hopital Tenon

Paris, , France

Site Status

CHU Poitiers

Poitiers, , France

Site Status

Institut Jean Godinot

Reims, , France

Site Status

CHU - Robert Debre

Reims, , France

Site Status

Centre Eugene Marquis

Rennes, , France

Site Status

Hopital Charles Nicolle

Rouen, , France

Site Status

Clinique Armoricaine De Radiologie

Saint-Brieuc, , France

Site Status

Centre Paul Strauss

Strasbourg, , France

Site Status

Institut Claudius Regaud

Toulouse, , France

Site Status

Clinique Du Parc

Toulouse, , France

Site Status

Centre Alexis Vautrin

Vandœuvre-lès-Nancy, , France

Site Status

Institut Gustave Roussy

Villejuif, , France

Site Status

Countries

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France

References

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Winter A, Cuer B, Conroy T, Juzyna B, Gourgou S, Mollevi C, Touraine C. Flexible modeling of longitudinal health-related quality of life data accounting for informative dropout in a cancer clinical trial. Qual Life Res. 2023 Mar;32(3):669-679. doi: 10.1007/s11136-022-03252-6. Epub 2022 Sep 17.

Reference Type DERIVED
PMID: 36115002 (View on PubMed)

Cuer B, Conroy T, Juzyna B, Gourgou S, Mollevi C, Touraine C. Joint modelling with competing risks of dropout for longitudinal analysis of health-related quality of life in cancer clinical trials. Qual Life Res. 2022 May;31(5):1359-1370. doi: 10.1007/s11136-021-03040-8. Epub 2021 Nov 24.

Reference Type DERIVED
PMID: 34817733 (View on PubMed)

Cuer B, Mollevi C, Anota A, Charton E, Juzyna B, Conroy T, Touraine C. Handling informative dropout in longitudinal analysis of health-related quality of life: application of three approaches to data from the esophageal cancer clinical trial PRODIGE 5/ACCORD 17. BMC Med Res Methodol. 2020 Sep 3;20(1):223. doi: 10.1186/s12874-020-01104-w.

Reference Type DERIVED
PMID: 32883216 (View on PubMed)

Conroy T, Galais MP, Raoul JL, Bouche O, Gourgou-Bourgade S, Douillard JY, Etienne PL, Boige V, Martel-Lafay I, Michel P, Llacer-Moscardo C, Francois E, Crehange G, Abdelghani MB, Juzyna B, Bedenne L, Adenis A; Federation Francophone de Cancerologie Digestive and UNICANCER-GI Group. Definitive chemoradiotherapy with FOLFOX versus fluorouracil and cisplatin in patients with oesophageal cancer (PRODIGE5/ACCORD17): final results of a randomised, phase 2/3 trial. Lancet Oncol. 2014 Mar;15(3):305-14. doi: 10.1016/S1470-2045(14)70028-2. Epub 2014 Feb 18.

Reference Type DERIVED
PMID: 24556041 (View on PubMed)

Other Identifiers

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FRE-FNCLCC- ACCORD-17-0707

Identifier Type: -

Identifier Source: secondary_id

EU-20848

Identifier Type: -

Identifier Source: secondary_id

CDR0000595050

Identifier Type: -

Identifier Source: org_study_id