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

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ClinicalTrials.gov Identifier: NCT00861094
Recruitment Status : Completed
First Posted : March 13, 2009
Last Update Posted : December 18, 2015
Sponsor:
Information provided by (Responsible Party):
UNICANCER

Study Description
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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.


Condition or disease Intervention/treatment Phase
Esophageal Cancer Drug: cisplatin Drug: 5-FU Drug: oxaliplatin Radiation: radiation therapy Drug: Folinic Acid Phase 2 Phase 3

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.

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 266 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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.
Study Start Date : March 2008
Actual Primary Completion Date : September 2011
Actual Study Completion Date : December 2012

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: 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
 Drug: 5-FU
Other Name: 5-Fluorouracil

Drug: oxaliplatin
Radiation: radiation therapy
Drug: Folinic Acid
Experimental: 5-FU / cisplatin and radiotherapy
5-FU (100mg/m2); Cisplatin (75mg/m2)
 Drug: cisplatin
Drug: 5-FU
Other Name: 5-Fluorouracil

Radiation: radiation therapy


Outcome Measures
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Primary Outcome Measures :
  1. Percentage of patients who complete the full study treatment (Phase II) [ Time Frame: 12 weeks ]
  2. Endoscopic complete response rate (Phase II) [ Time Frame: 12 weeks ]
  3. Progression-free survival (Phase III) [ Time Frame: Until progression ]

Secondary Outcome Measures :
  1. Safety profile as assessed by NCI CTC v2.0 (Phase II) [ Time Frame: Total duration of the trial ]
  2. Overall survival (Phase III) [ Time Frame: Total duration of the trial ]
  3. Complete response rate (Phase III) [ Time Frame: Total duration of the trial ]
  4. Time to treatment failure (Phase III) [ Time Frame: Total duration of the trial ]
  5. Incidence of grade 3-4 toxicities (Phase III) [ Time Frame: Total duration of the trial ]
  6. Quality of life as assessed by EORTC QLQ-C30 (version 3) and EORTC QLQ-OES18 (Phase III) [ Time Frame: Total duration of the trial ]

Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00861094


Locations
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Sponsors and Collaborators
UNICANCER
Investigators
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Principal Investigator: Thierry Conroy, MD Centre Alexis Vautrin
More Information
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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: UNICANCER
ClinicalTrials.gov Identifier: NCT00861094    
Other Study ID Numbers: CDR0000595050
FRE-FNCLCC- ACCORD-17-0707
EU-20848
First Posted: March 13, 2009    Key Record Dates
Last Update Posted: December 18, 2015
Last Verified: December 2015
Keywords provided by UNICANCER:
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
Additional relevant MeSH terms:
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Esophageal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Head and Neck Neoplasms
Digestive System Diseases
Esophageal Diseases
Gastrointestinal Diseases
Leucovorin
Folic Acid
Fluorouracil
Oxaliplatin
Levoleucovorin
 Antineoplastic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antidotes
Protective Agents
Vitamin B Complex
Vitamins
Micronutrients
Hematinics