Clinical trial NCT00209716: Phase I/II Study of Taxotere,CDDP and 5-FU(TPF) in Pre-treated Pts With Metastatic Esophageal Cancer.
Official title: Phase I/II Study of Docetaxel, Cisplatin and 5-fluorouracil(TPF) as Chemotherapy in Pre-treated Patients With Metastatic Esophageal Cancer.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Esophageal Cancer
Lead sponsor: Hokkaido Gastrointestinal Cancer Study Group
Sponsor class: OTHER
Collaborators: name: Hokkaido University Hospital
First posted: 2005-09-21
Enrollment: 30
Sex: ALL
Minimum age (years): 20
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: A phase I/II study is conducted to determine the maximum-tolerated dose (MTD), dose-limiting toxicity (DLT), and efficacy of a combination chemotherapy using docetaxel, cisplatin and 5-fluorouracil (TPF) in Pre-treated patients with metastatic esophageal cancer. The usefulness of the this regimen is evaluated by response rate, median survival time, and progression free survival.

Detailed description: Patients with pre-treated measurable metastatic esophageal cancer were included in this trial. Patients received this combination chemotherapy repeated every 28 days until progression disease. Starting dose (dose level 1) were docetaxel 30 mg/m2 on day 1, fixed dose intravenously cisplatin (15 mg/m2/day) and continuous infusion 5-FU (800 mg/m2/day) on day 1-4. DLT was defined as follows (according to NCI-CTC version 2.0); Grade 4 neutropenia lasting for more than 4days, Grade 4 anemia and thrombocytopenia, Grade 3 neutropenia accompanied fever (\>38℃) , and Grade 3 non-hematological toxicity (except for nausea, appetite loss , general fatigue). Maximal Tolerated Dose (MTD) is determined when the incidence of critical toxicity exceeds 50% at a certain dose level. Response rate will be calculated according to RECIST criteria.

Eligibility criteria: Inclusion Criteria:

* Histologically confirmed metastatic or recurrent esophageal tumors with previous treatment for advanced disease.(Except for small cell carcinoma)
* At least one measurable lesion according to the RECIST criteria. Minimum indicator lesion size: \> 10 mm measured by spiral CT or \>20mm measured by conventional techniques(Except for Phase I setting).
* Patients aged between 20 and 75 years, inclusive, at the time of acquisition of informed consent
* Patients with performance status(ECOG) 0 to 2
* Abnormal hematologic values (WBC ≥ 3.5 x 109/L, Hemoglobin ≥ 9.5g/dl, platelet count ≥ 100 x 109/L)
* Creatinine clearance ≥ 60 ml/min, Serum cleatinine ≤ 1.5mg/dl
* Serum bilirubin ≤ 1.5mg/dl. ALT, AST ≤ 2.5 x upper normal limit (or ≤ 3 x upper normal limit in the case of liver metastases)
* Patients who have received 1cycle cancer therapy (radiotherapy, chemotherapy or chemoradiotherapy) given \> 4 weeks prior to the beginning of study therapy
* Life expectancy ≥ 3 months
* Patients who have given written informed consent to participate in this study

Exclusion Criteria:

* Patients with active multiple cancers; or even if the multiple cancers are metachronous, have a disease-free period of less than 5 years (but excluding cancer in situ and skin cancer) (Except for Phase I setting)
* Serious, uncontrolled, concurrent infection(s) or illness(es)
* Patients with no serious concurrent complications (such as heart disease, Intestinal pneumonia)
* Patients with brain metastasis
* Patients receiving continuous administration of steroids
* Patients who have experienced serious drug allergy in the past
* Patients with retention of body fluid(pleural effusion, ascites, pericardial effusion) necessitating treatment
* Patients who are pregnant and lactating or hope to become pregnant during the study period
* Patients with prior Taxan treatment (Paclitaxel, Docetaxel)
* Patients with edema ≥ grade 2
* Others, patients judged by the investigator or subinvestigator to be inappropriate as subject

Primary outcomes:
measure: Determine the DLT(Dose Limiting Toxicity) and MTD(Maximum Tolerated Dose) in Phase I setting. Determine the clinical response rate with Recommended dose in Phase II setting.
timeFrame: 1 year
Secondary outcomes:
measure: Determine the clinical response rate of patients in Phase I setting.
timeFrame: 1-year
measure: Determine the MST(Median Survival Time) and PFS(Progression Free Survival) in Phase II setting.
timeFrame: 2-years
Other outcomes:
Locations:
city: Sapporo
country: Japan
facility: ・ Hokkaido University Hospital (Hokkaido University Graduate School of Medicine)
state: Hokkaido
Study officials:
affiliation: Hokkaido Gastrointestinal Cancer Study Group
name: Masahiro Asaka, MD, PhD
role: STUDY_CHAIR
References: