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.
18 Years
N/A
Both
Esophageal Cancer
Trial Information
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.
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.
Inclusion 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
Type of Study:
Interventional
Study Design:
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Percentage of patients who complete the full study treatment (Phase II)
Outcome Time Frame:
12 weeks
Safety Issue:
No
Principal Investigator
Thierry Conroy, MD
Investigator Role:
Principal Investigator
Investigator Affiliation:
Centre Alexis Vautrin
Authority:
France: AFFSAPS
Study ID:
CDR0000595050
NCT ID:
NCT00861094
Start Date:
March 2008
Completion Date:
December 2012
Related Keywords:
- Esophageal Cancer
- 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
- Esophageal Diseases
- Esophageal Neoplasms
Name | Location |
|---|
