Clinical trial NCT03301454: Study of the Interest of Pursuing or Not the Chemotherapy for Patients With Metastatic Esophageal Cancer
Official title: Phase II Randomized Study Measuring the Interest of Pursuing or Not the CT for Non-progressive Patients With Metastatic Esophageal Squamous-cell Cancer After 6 Weeks of LV5FU2-paclitaxel Given After a 1st Line Fluoropyrimidine/Pt Salt CT
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Esophageal Cancer, Squamous Cell
Lead sponsor: Centre Oscar Lambret
Sponsor class: OTHER
First posted: 2017-10-04
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Phase II study, randomized, open-label, multicentric, willing to establish the benefit of pursuing chemotherapy beyond 6 weeks for non progressive patients. The study will proceed in two successive phases :

* non randomized phase in which all patients will undergo chemotherapy
* second phase in which only non progressive patients are going to be randomized ("discontinuation design"). Patients that will show progression in their disease during the first 6 weeks will be released of the study

Detailed description: Initial phase: this part of the trial consist of 3 cycles of LV5FU2 (Bolus 5-FU 400mg/m² - 5-FU continuously during 46h: 3000 mg/m², calcium levofolinate 200 mg/m²) - paclitaxel (100 mg/m² at day 1) every 14 days. After 6 weeks,the phase will end with a check-up (clinical exam, tumor evaluation and biological test). Then, if the disease is non-progressive, the patient will proceed to the randomized phase.

Randomized phase:

* Arm A : pursuit of chemotherapy and best supportive care
* Arm B : interruption of chemotherapy and best supportive care

Eligibility criteria: Inclusion Criteria:

* Patients suffering from squamous-cell type esophageal cancer histologically proved
* Metastatic disease measurable according to RECIST criteria. Patients with metachronous metastasis and who have been treated with surgery (+/- radio chemotherapy concurrent or adjuvant chemotherapy) or exclusive radio chemotherapy, are eligible
* Patients who show progress under chemotherapy that associates a fluoropyrimidine with a platinum salt
* Man or woman over 18 years old
* ECOG performance status ≤ 2
* Adequate haematological, renal and hepatic functions : PNN ≥ 1500/ mm3; platelets ≥ 100 000/ mm3; Haemoglobin ≥ 9.0 g/dL; ALT and AST ≤ 2.5 ULN (≤ 5.0 in case of liver metastases); Total bilirubin ≤ 1.5 X ULN; Serum creatinine ≤ 1.5 ULN
* Efficient contraceptive method for both gender (if applicable), during the whole treatment period and the 6 months following the last treatment administration
* Affiliation to the National Social Security System
* With informed and signed consent

Inclusion Criteria for randomization:

* ECOG performance status ≤ 2
* Able to pursuit the LV5FU2-paclitaxel chemotherapy
* Non-progressive disease after the initial phase (first tumor exam at week 6)

Exclusion Criteria:

* Patients who received more than one line of chemotherapy for a metastatic disease
* Presence of other evolutive tumors
* Cerebral metastasis or other known brain tumors
* Severe liver failure
* Pernicious anemia or other anemia due to vitamin B12 defficiency
* Hypersensibility to an active substance or any other excipients of experimental drugs
* Every unstable chronicle diseases that can affect patient confidence or security
* Clinically significant active cardiac disease or myocardial infarction in the 6 previous months
* Patients with a known dihydropyrimidine dehydrogenase (DPD) deficiency
* Concomitant treatment with : sorivudin or analogs; prophylactic phenytoin
* Live attenuated vaccine within the 3 previous months
* Pregnant or breastfeeding women
* Unable to comply with the medical monitoring for geographic, social or mental issues
* Patient Under guardianship or tutorship

Primary outcomes:
measure: Estimate the overall survival for patients suffering from Esophageal cancer
timeFrame: From date of randomization until the date of death from any cause, up to 8 months after the beginning of the treatment
Secondary outcomes:
measure: Estimate efficiency in term of overall survival, of pursuing chemotherapy
timeFrame: From date of randomization until the date of death from any cause, up to 8 months after the beginning of the treatment
measure: Estimate the efficiency in term of progression-free of pursuing chemotherapy
timeFrame: From date of randomization until the date of first documented progression or date of death from any cause, up to 8 months after the beginning of the treatment
measure: Estimate the rate of non progressive patients
timeFrame: From date of inclusion until the date of the end the 6 firsts weeks of treatment
measure: Estimate the overall survival of the whole study population
timeFrame: From date of inclusion until the date of death from any cause, up to 8 months after the beginning of the treatment
measure: Measure the toxicity of chemotherapy
timeFrame: from baseline up to 12 months
measure: Estimate the consequences of pursuing chemotherapy
timeFrame: From date of randomization until the date of first documented progression or date of death from any cause, up to 8 months after the beginning of the treatment
Other outcomes:
Locations:
city: Amiens
country: France
facility: Centre Hospitalier Universitaire
city: Angers
country: France
facility: Centre Paul Papin
city: Caen
country: France
facility: Centre François Baclesse
city: Lille
country: France
facility: Centre Oscar Lambret
city: Nantes
country: France
facility: Centre René Gauducheau
city: Plérin
country: France
facility: Centre Armoricain de Radiothérapie, Imagerie médicale et Oncologie
city: Rennes
country: France
facility: Centre Eugène Marquis
Study officials:
affiliation: Centre Oscar Lambret
name: Farid EL HAJBI, MD
role: PRINCIPAL_INVESTIGATOR
References: