Docetaxel and S-1 for Advanced Esophageal Cancer

A Phase II Study of Docetaxel and S-1 as First-line Chemotherapy in Patients With Advanced Esophageal Cancer

This study will evaluate the efficacy of docetaxel and S-1 combination chemotherapy in Korean patients with esophageal cancer.

Study Overview

• Status: Unknown
• Conditions: Esophageal Neoplasms
• Intervention / Treatment: Drug: DS (docetaxel+S-1)

Detailed Description

Esophageal cancer is the ninth most common cancer in male population in Korea. It was estimated that 1,864 new cases of esophageal cancer were reported and 1,434 deaths occurred in Korea in 2005.

Although half of the patients with esophageal cancer initially present with locoregional disease amenable to radical surgery or radiation-based therapy, most patients eventually develop metastatic disease with or without local recurrence.

Chemotherapy plays a major role in palliative therapy and remains to be the primary mode of treatment for the recurrent or metastatic esophageal cancer. Although various chemotherapy regimens are available, esophageal cancer carries a very poor prognosis, with a mean survival time of less than 8.1 months with current chemotherapies used singly or in combination with 5-fluorouracil (5-FU), vindesine, mitomycin, docetaxel, paclitaxel, cisplatin, irinotecan, vinorelbine, or capecitabine. The majority of the trials performed were in small numbers of patients with reported response rates from 15 to 40%.

The response was usually of short duration and there was no survival benefit with single agent chemotherapy. Combination chemotherapy has slightly improved the results in terms of duration of response (3-6 months), but still there was little improvement in overall survival. Therefore, the identification of new active agents is essential to prolong the survival.

Clinical trials of single agent docetaxel have been reported in patients with esophageal cancer and the response rate is about 18-25%.

S-1, a new biochemical modulator of 5-FU, is an oral dihydropyrimidine dehydrogenase(DPD) inhibitory fluoropyrimidine. The advantages of S-1 compared with 5-FU are greater convenience because of its oral formulation and continuous delivery, without intravenous infusion. S-1 is frequently used as a substitute for 5-FU in gastric cancer, but limited data is available for esophageal cancer.

The combination of docetaxel and S-1 is highly active and well tolerated in advanced or recurrent gastric cancer, and the synergistic antitumor activity has been fully elucidated.

Therefore, we will evaluate the efficacy of docetaxel and S-1 combination chemotherapy in Korean patients with esophageal cancer.

• Study Type: Interventional
• Enrollment (Anticipated): 37
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Dae Young Zang, MD, PhD; Phone Number: 82313803871; Email: fhdzang@hallym.or.kr
• Study Contact Backup: Name: Jin Hee Jung, RN; Phone Number: 82313803704; Email: jhjung23@daum.net

Study Locations

• Korea, Republic of
  • Anyang, Korea, Republic of
    • Recruiting
    • Hallym University Medical Center
    • Contact: Dae Young Zang, MD, PhD; Phone Number: 82313803871; Email: fhdzang@hallym.or.kr
    • Contact: Jin Hee Jung, RN; Phone Number: 82313803704; Email: jhjung23@daum.net
    • Sub-Investigator: Hyeong Su Kim, MD
    • Sub-Investigator: Boram Han, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Pathologically confirmed squamous cell carcinoma or adenocarcinoma of esophagus.
• Unresectable locally advanced, recurrent or metastatic disease.
• Measurable or evaluable disease by RECIST criteria 1.1.
• Minimum age of 18 years.
• ECOG Performance status 0-2.
• Prior chemotherapy is not allowed.
• More than 4 weeks since completion of prior radiotherapy (measurable or evaluable lesions are outside the radiation field)
• Adequate organ functions
• Patients must sign an informed consent indicating that they are aware of the investigational nature of the study in keeping with the policy of the hospital

Exclusion Criteria:

• Other tumor type than squamous cell carcinoma and adenocarcinoma
• Previous history of chemotherapy except neoadjuvant or adjuvant chemotherapy without docetaxel and S-1
• Obvious bowel obstruction unrelieved by proper management
• Evidence of serious gastrointestinal bleeding
• Patients with CNS metastases
• Patients with active infection, severe heart disease, uncontrollable hypertension or diabetes mellitus, myocardial infarction during the preceding 6 months, pregnancy, or breast feeding
• Any previous or concurrent malignancy other than non-melanoma skin cancer or in situ cancer of uterine cervix
• Known history of cerebral or leptomeningeal metastases or neurologic disease

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: DS (docetaxel+S-1); Treatment will be delivered as a 3-week cycle.; Docetaxel 60 mg/m²IV on day 1; S-1 80 mg/m2/day PO on day 1-14	Drug: DS (docetaxel+S-1); Treatment will be delivered as a 3-week cycle.; Docetaxel 60 mg/m²IV on day 1; S-1 80 mg/m2/day PO on day 1-14; Other Names: Taxotere; TS-1

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate	Objective response rate will be measured from the rate of complete response (disappearance of disease) and partial response (decrease at least 30% in the sum of the longest diameters of target lesions) by RECIST (response evaluation criteria in solid tumors) guidelines.	1.5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression free survival	Progression free survival time will be measured from the start of study treatment until documented tumor progression, or death due to any cause	1.5 years
Overall survival	Overall survival time will be measured from the start of study treatment until death due to any cause	1.5 years
Toxicity profiles	adverse events will be descripted and graded using NCI-CTCAE version 4.0	1.5 years
Disease control rate	Disease control rate will be measured from the rate of complete response (disappearance of disease), partial response (decrease at least 30% in the sum of the longest diameters of target lesions), and stable disease (neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD) by RECIST (response evaluation criteria in solid tumors) guidelines.	1.5 years

Collaborators and Investigators

• Sponsor: Hallym University Medical Center
• Collaborators: Jeil Pharmaceutical Co., Ltd.

Study record dates

Study Major Dates

• Study Start: November 1, 2011
• Primary Completion (ANTICIPATED): June 1, 2018
• Study Completion (ANTICIPATED): June 1, 2018

Study Registration Dates

• First Submitted: September 20, 2012
• First Submitted That Met QC Criteria: September 22, 2012
• First Posted (ESTIMATE): September 26, 2012

Study Record Updates

• Last Update Posted (ACTUAL): August 23, 2017
• Last Update Submitted That Met QC Criteria: August 22, 2017
• Last Verified: August 1, 2017

More Information

Terms related to this study

• Keywords: Docetaxel; S-1; Esophageal neoplasms
• 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; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Docetaxel
• Other Study ID Numbers: HMC-HO-GI-1202

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED