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Esophageal CancerPhase 2/3NCT00861094

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

A Phase 2/3 study testing cisplatin, 5-FU and oxaliplatin in people with Esophageal Cancer, run by UNICANCER at 28 sites in France.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Esophageal Cancer
What is being tested?
cisplatin, 5-FU and oxaliplatin
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
266 participants
Where
28 sitesFrance
Study dates
Mar 2008to Dec 2012
Phase
Phase 2/3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

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

Trial locations and contacts

28 sites in 1 country.

28 sites in 1 country

France28 sites

  • CHR de Besancon - Hopital Saint-Jacques

    Besançon, 25030

  • Hopital Saint Andre

    Bordeaux, 33075

  • Institut Bergonie

    Bordeaux, 33076

  • Hopital Ambroise Pare

    Boulogne-Billancourt, F-92104

  • Polyclinique Du Parc

    Caen, 14052

  • Centre Regional Francois Baclesse

    Caen, 14076

  • Hopital Du Bocage

    Dijon, 21034

  • Centre de Lutte Contre le Cancer Georges-Francois Leclerc

    Dijon, 21079

  • Centre Oscar Lambret

    Lille, 59020

  • Centre Hospital Regional Universitaire de Limoges

    Limoges, 87042

  • Centre Leon Berard

    Lyon, 69373

  • CHU de la Timone

    Marseille, 13385

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

    Montpellier, 34298

  • Centre Antoine Lacassagne

    Nice, 06189

  • Hopital Europeen Georges Pompidou

    Paris, 75015

  • Hopital Saint-Louis

    Paris, 75475

  • Hopital Tenon

    Paris, 75970

  • CHU Poitiers

    Poitiers, 86021

  • Institut Jean Godinot

    Reims, 51056

  • CHU - Robert Debre

    Reims, 51092

  • Centre Eugene Marquis

    Rennes, 35042

  • Hopital Charles Nicolle

    Rouen, 76031

  • Clinique Armoricaine De Radiologie

    Saint-Brieuc, F-22015

  • Centre Paul Strauss

    Strasbourg, 67065

  • Institut Claudius Regaud

    Toulouse, 31052

  • Clinique Du Parc

    Toulouse, 31078

  • Centre Alexis Vautrin

    Vandœuvre-lès-Nancy, 54511

  • Institut Gustave Roussy

    Villejuif, F-94805

Other trials in France

About this study

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.

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.

Read the 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.

Being tested
cisplatin, 5-FU, oxaliplatin, radiation therapy, Folinic Acid
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
Medical subject headings
Esophageal Neoplasms, Adenocarcinoma Of Esophagus, Esophageal Squamous Cell Carcinoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Study groups in NCT00861094
Study groupRoleWhat they receive
FOLFOX and radiotherapyExperimentalOxaliplatin (85mg/m2); Folinic Acid (200mg/m2); 5-FU (400mg/m2-Bolus and 1600mg/m2 over 46h)- once every two weeks for six cycles
Receives: Drug: 5-FU; Drug: oxaliplatin; Radiation: radiation therapy; Drug: Folinic Acid
5-FU / cisplatin and radiotherapyExperimental5-FU (100mg/m2); Cisplatin (75mg/m2)
Receives: Drug: cisplatin; Drug: 5-FU; Radiation: radiation therapy

What is being measured

The primary outcome is the main question the study is designed to answer.

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

    Measured: 12 weeks

  2. Endoscopic complete response rate (Phase II)

    Measured: 12 weeks

  3. Progression-free survival (Phase III)

    Measured: Until progression

Secondary outcomes (6)

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

    Measured: Total duration of the trial

  2. Overall survival (Phase III)

    Measured: Total duration of the trial

  3. Complete response rate (Phase III)

    Measured: Total duration of the trial

  4. Time to treatment failure (Phase III)

    Measured: Total duration of the trial

  5. Incidence of grade 3-4 toxicities (Phase III)

    Measured: Total duration of the trial

  6. Quality of life as assessed by EORTC QLQ-C30 (version 3) and EORTC QLQ-OES18 (Phase III)

    Measured: Total duration of the trial

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted13 Mar 2009 (estimated)
  2. Study startMar 2008
  3. Primary completionSep 2011
  4. Study completionDec 2012

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2/3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
266 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00861094
Sponsor's protocol ID
CDR0000595050
Other IDs
FRE-FNCLCC- ACCORD-17-0707, EU-20848
Status last verified
Dec 2015
First submitted
12 Mar 2009
Last updated
18 Dec 2015
Results posted
No
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 36115002

  • 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.

    PubMed 34817733

  • 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.

    PubMed 32883216

  • 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.

    PubMed 24556041

Questions about this trial

What is this clinical trial studying?

A Phase 2/3 study testing cisplatin, 5-FU and oxaliplatin in people with Esophageal Cancer, run by UNICANCER at 28 sites in France.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 18 Dec 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 28 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percentage of patients who complete the full study treatment (Phase II) (time frame: 12 weeks). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00861094, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Dec 2015.

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