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

NCT00861094 | Completed Phase 2 DMC

• 3 other identifiers: CDR0000595050FRE-FNCLCC- ACCORD-17-0707EU-20848
• Study Type: interventional
• Target: 266
• Locations: 1 country
• Sites: 28

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.

Conditions

Esophageal Cancer

Keywords

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

Outcome Measures

Primary Outcomes (3)

• Percentage of patients who complete the full study treatment (Phase II)

  12 weeks

• Endoscopic complete response rate (Phase II)

  12 weeks

• Progression-free survival (Phase III)

  Until progression

Secondary Outcomes (6)

• Safety profile as assessed by NCI CTC v2.0 (Phase II)

  Total duration of the trial

• Overall survival (Phase III)

  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

• Incidence of grade 3-4 toxicities (Phase III)

  Total duration of the trial

Study Arms (2)

FOLFOX and radiotherapy

EXPERIMENTAL

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; Drug: oxaliplatin; Radiation: radiation therapy; Drug: Folinic Acid

5-FU / cisplatin and radiotherapy

EXPERIMENTAL

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

Drug: cisplatin; Drug: 5-FU; Radiation: radiation therapy

Interventions

cisplatin DRUG

5-FU / cisplatin and radiotherapy

5-FU DRUG

Also known as: 5-Fluorouracil

5-FU / cisplatin and radiotherapy; FOLFOX and radiotherapy

oxaliplatin DRUG

FOLFOX and radiotherapy

radiation therapy RADIATION

5-FU / cisplatin and radiotherapy; FOLFOX and radiotherapy

Folinic Acid DRUG

FOLFOX and radiotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• UNICANCER: lead

Study Sites (28)

CHR de Besancon - Hopital Saint-Jacques

Besançon, 25030, France

Location

Hopital Saint Andre

Bordeaux, 33075, France

Location

Institut Bergonie

Bordeaux, 33076, France

Location

Hopital Ambroise Pare

Boulogne-Billancourt, F-92104, France

Location

Polyclinique Du Parc

Caen, 14052, France

Location

Centre Regional Francois Baclesse

Caen, 14076, France

Location

Hopital Du Bocage

Dijon, 21034, France

Location

Centre de Lutte Contre le Cancer Georges-Francois Leclerc

Dijon, 21079, France

Location

Centre Oscar Lambret

Lille, 59020, France

Location

Centre Hospital Regional Universitaire de Limoges

Limoges, 87042, France

Location

Centre Leon Berard

Lyon, 69373, France

Location

CHU de la Timone

Marseille, 13385, France

Location

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

Montpellier, 34298, France

Location

Centre Antoine Lacassagne

Nice, 06189, France

Location

Hopital Europeen Georges Pompidou

Paris, 75015, France

Location

Hopital Saint-Louis

Paris, 75475, France

Location

Hopital Tenon

Paris, 75970, France

Location

CHU Poitiers

Poitiers, 86021, France

Location

Institut Jean Godinot

Reims, 51056, France

Location

CHU - Robert Debre

Reims, 51092, France

Location

Centre Eugene Marquis

Rennes, 35042, France

Location

Hopital Charles Nicolle

Rouen, 76031, France

Location

Clinique Armoricaine De Radiologie

Saint-Brieuc, F-22015, France

Location

Centre Paul Strauss

Strasbourg, 67065, France

Location

Institut Claudius Regaud

Toulouse, 31052, France

Location

Clinique Du Parc

Toulouse, 31078, France

Location

Centre Alexis Vautrin

Vandœuvre-lès-Nancy, 54511, France

Location

Institut Gustave Roussy

Villejuif, F-94805, France

Location

Related Publications (4)

• 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.

  PMID: 36115002 DERIVED

• 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.

  PMID: 34817733 DERIVED

• 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.

  PMID: 32883216 DERIVED

• 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.

  PMID: 24556041 DERIVED

MeSH Terms

Conditions

Esophageal Neoplasms; Adenocarcinoma Of Esophagus; Esophageal Squamous Cell Carcinoma

Interventions

Cisplatin; Fluorouracil; Oxaliplatin; Radiotherapy; Leucovorin

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases; Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms, Squamous Cell

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Coordination Complexes; Organic Chemicals; Therapeutics; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes

Study Officials

• Thierry Conroy, MD

  Centre Alexis Vautrin

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 12, 2009
• First Posted: March 13, 2009
• Study Start: March 1, 2008
• Primary Completion: September 1, 2011
• Study Completion: December 1, 2012
• Last Updated: December 18, 2015

Record last verified: 2015-12

Locations

FR (28)