Phase II Trial of XP Versus XG in Advanced Esophageal Squamous Cell Carcinoma

A Randomized Phase II Trial of Capecitabine Plus Cisplatin (XP) Versus Capecitabine Plus Genexol (XG) as a First-line Treatment for Advanced or Recurrent Esophageal Squamous Cell Carcinoma

Until today, the 5-FU/cisplatin combination is the reference regimen with 30-45% response rates, which is most commonly used to treat patients with metastatic, recurrent or locally advanced, unresectable squamous cell carcinoma of the esophagus. Because the classical dose schedule of this two-drug combination is cisplatin 100 mg/m2 day 1 and 5-FU 1000 mg/m2/day continuous infusion for 96-120 hr, prolonged administration time and mucosal toxicity are inconvenient to the patients with the aim of palliation. Capecitabine, which is oral prodrug of 5-FU and mimic continuously-infused 5-FU, is being investigated in phase I, II and III trials for the treatment of gastric, gastroesophageal, and esophageal cancers, primarily in the first-line metastatic setting but also in the adjuvant setting. In the investigators experience, capecitabine plus cisplatin combination (XP) as a first-line treatment for 45 patients with advanced or recurrent esophageal squamous cell carcinoma demonstrated a promising anti-tumor activity with 57% of response rate and showed tolerable toxicity with convenience.

Paclitaxel has been also investigated as monotherapy and in combination with cisplatin in patients with advanced esophageal cancer. A Dutch phase II study demonstrated that paclitaxel combination with carboplatin had shown an encouraging confirmed response rate of 59% with 51 patients with resectable esophageal cancer in neoadjuvant setting. Another Dutch phase II study showed 43% of response rate including 4% of CR with 8 months of response duration when paclitaxel plus cisplatin administration was given for patients with metastatic esophageal cancer. Although recently first-line palliative chemotherapy regimen in esophageal cancer has been investigated, many trials have failed to show superiority to 5-FU/cisplatin combination. Since the investigators considered that XP or XG (genexol) is more effective and convenient chemotherapy regimen than 5-FU/cisplatin, this randomized phase II study was planned to compare XP with XG in terms of efficacy and tolerability.

Study Overview

• Status: Completed
• Conditions: Advanced or Recurrent Esophageal Squamous Cell Carcinoma
• Intervention / Treatment: Drug: Capecitabine/Cisplatin(XP); Drug: Capecitabine/Paditaxel(XG)

• Study Type: Interventional
• Enrollment (Actual): 64
• Phase: Phase 2

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of
    • Samsung Medical Center

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

• Histologically confirmed metastatic, or recurrent esophageal squamous cell carcinoma
• Age > 18 years
• ECOG performance status 0 - 2
• At least one measurable lesion(s) by RECIST criteria
• Life expectancy ≥ 3 months
• No prior palliative chemotherapy
• Patients may have received prior adjuvant chemotherapy with 5-FU with cisplatin as long as it has been 6months since completion of regimen.
• Adequate bone marrow function (≥ ANC 1,500/ul, ≥ platelet 100,000/ul, ≥ Hb 9.0 g/dl)
• Adequate renal function (≤ serum creatinine 1.5 mg/dl or CCr ≥ 50 ml/min)
• Adequate liver function (≤ serum bilirubin 1.5 mg/dl, ≤ AST/ALT x 3 UNL)
• Written informed consent

Exclusion Criteria:

• Other tumor type than squamous cell carcinoma
• CNS metastasis
• Contraindication to any drug contained in the chemotherapy regimen
• Previous adjuvant treatment with 5-FU, cisplstin, capecitabine or paclitaxel finished less than 1 year6 months
• Evidence of serious gastrointestinal bleeding
• History of another malignancy within the last five years except cured
• basal cell carcinoma of skin and cured carcinoma in-situ of uterine cervix
• Clinically significant cardiac disease
• Serious pulmonary conditions/illness
• Serious metabolic disease such as severe non-compensated diabetes mellitus
• History of significant neurologic or psychiatric disorders
• Serious uncontrolled intercurrent infections, or other serious uncontrolled concomitant disease
• Positive serology for the HIV
• Pregnancy, breast feeding patient

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Capecitabine/Cisplatin(XP); Capecitabine AND Cisplatin	Drug: Capecitabine/Cisplatin(XP); Capecitabine/Cisplatin(XP) D1-D14 Capecitabine 2000mg/m2 D#2 PO D1 Cisplatin 75mg/m2 iv q 3 weeks
ACTIVE_COMPARATOR: Capecitabine/Paditaxel(XG); Capecitabine + Paditaxel(genexol)	Drug: Capecitabine/Paditaxel(XG); Capecitabine/Paditaxel(XG) D1-D14 Capecitabine 2000mg/m2 D#2 PO D1,D8 Paditaxel(genexol) 80mg/m2 iv q 3 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
response rate	12 months

Secondary Outcome Measures

Outcome Measure	Time Frame
progression free survival	12 months
overall survival	12 months
quality of life	12 months
Number of Adverse Event	12 months
predictive marker	12 months

Collaborators and Investigators

• Sponsor: Samsung Medical Center

Study record dates

Study Major Dates

• Study Start: September 1, 2008
• Primary Completion (ACTUAL): September 1, 2013
• Study Completion (ACTUAL): May 1, 2014

Study Registration Dates

• First Submitted: November 10, 2011
• First Submitted That Met QC Criteria: November 15, 2011
• First Posted (ESTIMATE): November 18, 2011

Study Record Updates

• Last Update Posted (ESTIMATE): December 29, 2015
• Last Update Submitted That Met QC Criteria: December 28, 2015
• Last Verified: December 1, 2015

More Information

Terms related to this study

• Keywords: Capecitabine; Cisplatin; Advanced or recurrent esophageal squamous cell carcinoma; Randomizes phase II trial; Genexol
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Disease Attributes; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Head and Neck Neoplasms; Esophageal Diseases; Neoplasms, Squamous Cell; Esophageal Neoplasms; Carcinoma; Recurrence; Carcinoma, Squamous Cell; Esophageal Squamous Cell Carcinoma; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Cisplatin; Capecitabine
• Other Study ID Numbers: 2011-09-10