Phase I/II Study of Taxotere,CDDP and 5-FU(TPF) in Pre-treated Pts With Metastatic Esophageal Cancer.

Phase I/II Study of Docetaxel, Cisplatin and 5-fluorouracil(TPF) as Chemotherapy in Pre-treated Patients With Metastatic Esophageal Cancer.

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.

Study Overview

• Status: Completed
• Conditions: Esophageal Cancer
• Intervention / Treatment: Drug: Taxotere; Drug: 5-Fluorouracil; Drug: Briplatin

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.

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Japan
  • Hokkaido
    • Sapporo, Hokkaido, Japan, 060-8638
      • ・ Hokkaido University Hospital (Hokkaido University Graduate School of Medicine)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1	Drug: Taxotere; 30 mg/m2, IV (in the vein) on day 1 of each 28 day cycle.; Other Names: Docetaxel; Drug: 5-Fluorouracil; 800 mg/m2, CIV (CIV.in the vein) on day 1~5 of each 28 day cycle.; Other Names: fluorouracil; Drug: Briplatin; 15 mg/m2, IV (in the vein) on day 1~4 of each 28 day cycle.; Other Names: Cisplatin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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.	1 year

Secondary Outcome Measures

Outcome Measure	Time Frame
Determine the clinical response rate of patients in Phase I setting.	1-year
Determine the MST(Median Survival Time) and PFS(Progression Free Survival) in Phase II setting.	2-years

Collaborators and Investigators

• Sponsor: Hokkaido Gastrointestinal Cancer Study Group
• Collaborators: Hokkaido University Hospital
• Investigators: Study Chair: Masahiro Asaka, MD, PhD, Hokkaido Gastrointestinal Cancer Study Group

Study record dates

Study Major Dates

• Study Start: December 1, 2003
• Primary Completion (Actual): October 1, 2009
• Study Completion (Actual): November 1, 2009

Study Registration Dates

• First Submitted: September 13, 2005
• First Submitted That Met QC Criteria: September 13, 2005
• First Posted (Estimate): September 21, 2005

Study Record Updates

• Last Update Posted (Estimate): May 26, 2010
• Last Update Submitted That Met QC Criteria: May 24, 2010
• Last Verified: May 1, 2010

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Head and Neck Neoplasms; Esophageal Diseases; Esophageal Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Docetaxel; Cisplatin; Fluorouracil
• Other Study ID Numbers: HGCSG0305-2; TPF-2