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

Esophageal Cancer Clinical Trial

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00861094
• Other study ID #: CDR0000595050
• Secondary ID: FRE-FNCLCC- ACCO
• Status: Completed
• Phase: Phase 2/Phase 3
• First received: March 12, 2009
• Last updated: December 17, 2015
• Start date: March 2008
• Est. completion date: December 2012

Study information

• Verified date: December 2015
• Source: UNICANCER
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: AFFSAPS
• Study type: Interventional

Clinical 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. 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.

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 information / eligibility

• Status: Completed
• Enrollment: 266
• Est. completion date: December 2012
• Est. primary completion date: September 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Esophageal Cancer
• Esophageal Neoplasms

Intervention

Drug:
• cisplatin

• 5-FU

• oxaliplatin

Radiation:
• radiation therapy

Drug:
• Folinic Acid

Locations

Country	Name	City	State
France	CHR de Besancon - Hopital Saint-Jacques	Besancon
France	Hopital Saint Andre	Bordeaux
France	Institut Bergonie	Bordeaux
France	Hopital Ambroise Pare	Boulogne-Billancourt
France	Centre Regional Francois Baclesse	Caen
France	Polyclinique Du Parc	Caen
France	Centre de Lutte Contre le Cancer Georges-Francois Leclerc	Dijon
France	Hopital Du Bocage	Dijon
France	Centre Oscar Lambret	Lille
France	Centre Hospital Regional Universitaire de Limoges	Limoges
France	Centre Leon Berard	Lyon
France	CHU de la Timone	Marseille
France	Centre Regional de Lutte Contre le Cancer - Centre Val d'Aurelle	Montpellier
France	Centre Antoine Lacassagne	Nice
France	Hopital Europeen Georges Pompidou	Paris
France	Hopital Saint-Louis	Paris
France	Hopital Tenon	Paris
France	CHU Poitiers	Poitiers
France	CHU - Robert Debre	Reims
France	Institut Jean Godinot	Reims
France	Centre Eugene Marquis	Rennes
France	Hopital Charles Nicolle	Rouen
France	Clinique Armoricaine De Radiologie	Saint Brieuc
France	Centre Paul Strauss	Strasbourg
France	Clinique Du Parc	Toulouse
France	Institut Claudius Regaud	Toulouse
France	Centre Alexis Vautrin	Vandoeuvre-les-Nancy
France	Institut Gustave Roussy	Villejuif

Sponsors (1)

Lead Sponsor	Collaborator
UNICANCER

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of patients who complete the full study treatment (Phase II)		12 weeks	No
Primary	Endoscopic complete response rate (Phase II)		12 weeks	No
Primary	Progression-free survival (Phase III)		Until progression	No
Secondary	Safety profile as assessed by NCI CTC v2.0 (Phase II)		Total duration of the trial	Yes
Secondary	Overall survival (Phase III)		Total duration of the trial	No
Secondary	Complete response rate (Phase III)		Total duration of the trial	No
Secondary	Time to treatment failure (Phase III)		Total duration of the trial	No
Secondary	Incidence of grade 3-4 toxicities (Phase III)		Total duration of the trial	Yes
Secondary	Quality of life as assessed by EORTC QLQ-C30 (version 3) and EORTC QLQ-OES18 (Phase III)		Total duration of the trial	No