Combination Treatment of S-1 With Paclitaxel in Advanced Esophageal Cancer

NCT01704690 | Terminated Phase 2 DMC

• 1 other identifier: ESCC001
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

Brief Summary

Esophageal cancer is one of the common malignant disease, especially in China. The annual incidence of esophageal squamous cell carcinoma is 260,000 with the motility of 210,000. The prognosis of esophageal cancer is very poor. About 50% of patients have advanced disease at diagnosis and the natural course is only 6-8 months with a 5-year survival rate of 5-7%. Though some patients received surgical treatment, disease will recurrent and metastasis in nearly 90% of the patients. In past decades, there isn't much improvement of the outcome and survival of advanced esophageal cancer due to the lack of effective chemotherapy agents. The traditional chemotherapy drugs include 5-fluorouracil and cisplatin and the combination of them results in a 25-35% response rate in both first-line and palliative treatment. Paclitaxel plus cisplatin regiment is another promising treatment of esophageal cancer and have been proved effective in many studies. One of our previous study showed paclitaxel and cisplatin treatment resulted in encouraging response rate with manageable side-effects in 131 patients of advanced esophageal cancer. However, the toxicities of paclitaxel and cisplatin limit their combination in clinic. For example, the polyoxyethylene castor oil paclitaxel could induce acute hypersensitivity reactions and neurotoxicity. Cisplatin could result in dysfunction of kidney and neurotoxicity. In addition, most of esophageal cancer patients are age 65 to 70. Many of them have simultaneously other diseases such as hypertension, diabetes, and chronic kidney disease which cause varying damages of renal function and limit the use of cisplatin in these patients. Therefore, it is urgent for doctors to seek an alternative of cisplatin in the combination chemotherapy treatment. Therefore, the investigators designed this randomized clinical trial in which a novel combination of S-1 with paclitaxel is used to treat advanced esophageal cancer patients in compare with paclitaxel/cisplatin and 5-FU/cisplatin treatment to explore its efficacy and toxicity. The investigators hope this study will provide some clues for the treatment of esophageal cancer patients.

Conditions

Esophageal Cancer

Keywords

Esophageal cancer; Chemotherapy; Efficacy; Toxicity

Outcome Measures

Primary Outcomes (1)

• Response rate

  The disease control rate (DCR) will be evaluated every 2 cycles (average 6 weeks) of treatment according to the RECIST 1.0 criteria until disease progression or finishing all 6 cycles of treatment.

  Every 2 cycles of treatment (average 6 weeks) up to 6cycles (assessed 18 weeks)

Secondary Outcomes (3)

• The median overall survival time

  From date of randomization until the date of death from any cause (assessed up to 36 months)

• Median progression-free time

  From date of randomization until the date of first documented progression or death from any cause (assessed up tp 36 months)

• Number of Participants with Adverse Events and the degree of each adverse event

  Participants will be followed every week during treatment and every 3 months during follow-up time (assessed up to 1 year)

Study Arms (3)

S-1 and Paclitaxel

EXPERIMENTAL

Patients in these arm will receive combination treatment of S-1 and paclitaxel. S-1, 80-120mg po, bid, from day 1 to day 14 Paclitaxel, 175mg/m2, IV infusion on day 1 Repeated every 21 days

Drug: S-1 and Paclitaxel

Paclitaxel and Cisplatin

ACTIVE COMPARATOR

Patients in these arm will receive combination treatment of paclitaxel and cisplatin. Paclitaxel, 175mg/m2, IV infusion on day 1 Cisplatin, 30 mg/m2, IV infusion on day 1 and day 2 Repeated every 21 days

Drug: Paclitaxel and Cisplatin

5-FU and Cisplatin

ACTIVE COMPARATOR

Patients in these arm will receive combination treatment of 5-FU and cisplatin. 5-FU, 2500mg/m2, continue iv infusion for 120 hours Cisplatin, 35 mg/m2, IV infusion on day 1 and day 2 Repeated every 21 days

Drug: 5-FU and Cisplatin

Interventions

S-1 and Paclitaxel DRUG

S-1 and Paclitaxel are used in the S-1 and Paclitaxel arm.

Also known as: TEYSUNO, TAXOL

S-1 and Paclitaxel

Paclitaxel and Cisplatin DRUG

The paclitaxel and cisplatin combination will be used in the Paclitaxel and Cisplatin arm.

Also known as: TAXOL, PLATINOL

Paclitaxel and Cisplatin

5-FU and Cisplatin DRUG

The cisplatin and 5-fluorouracil combination will be used in the Cisplatin and 5-FU arm.

Also known as: 5-fluorouracil, PLATINOL

5-FU and Cisplatin

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients who have histologically confirmed diagnosis of esophageal cancer without prior palliative treatment or an interval of at least 6 months from the last operation, adjuvant radiation therapy and adjuvant chemotherapy. If patients received adjuvant chemotherapy, paclitaxel and cisplatin must be excluded from the regiment or the total dosage of cisplatin must be less than 300mg/m2.
• \- Patients must be 18 to 75 years old and both genders are eligible.
• \- Patients must have measurable or evaluable disease with at least one tumor mass maximum diameter ≥10mm by multi-slice spiral CT or MR scan. If ordinary CT scan is used the tumor mass maximum diameter must ≥ 2cm. Imaging exam must be performed within 15 days from enrollment.
• \- Patients must have an expected life expectancy of ≥ 3 months
• \- Patients must have a performance status of ≥ 80 on the Karnofsky scale
• \- Patients must have normal marrow function and the blood tests must be collected within 7 days from enrollment with a hemoglobin (HGB) of ≥90g/L, an white blood cell (WBC) counts of ≥4.0×109/L，a neutrophil count of ≥2.0×109/L, , a platelet count of ≥100×109/L, a total bilirubin (TBil) of ≤1.0 upper normal limitation (UNL), a creatinine (Cr) of ≤ 1.0 UNL, alanine aminotransferase (ALAT) and aspartate aminotransferase (ASAT) of ≤2.5 UNL, Alkaline phosphatase (AKP) ≤5.0 UNL. For patients with liver metastasis, the ASAT/ALAT must be ≤5.0 UNL.
• \- Patients must have normal electrocardiogram results and no history of congestive heart failure.
• \- Patients must be with good compliance and agree to accept follow-up of disease progression and adverse events.
• \- Patients must give written informed consent signed voluntarily by patients themselves or their supervisors witted by doctors

You may not qualify if:

• Patients who have received prior palliative treatment or less than 6 months from the last operation, adjuvant radiotherapy, adjuvant chemotherapy.
• Previous treatment regiment involve paclitaxel and S-1
• Tumor mass \>10mm by CT or MR scan. The total area of metastatic tumor lesions in liver is over 50% of whole liver or the total area of metastatic tumor lesions in lung is over 25% of whole lung.
• Patients without measurable or evaluable disease, for example cavity effusion or diffusive metastasis of organs.
• Patients with history of other tumors except for those of cervical carcinoma in situ or skin basal cell carcinoma who had been completely treated and without relapse in last 5 years.
• Patients with serious diseases such as congestive heart failure, uncontrolled myocardial infarction and arrhythmia, liver failure and renal failure.
• Patients with only brain metastasis or bone metastasis
• Patients with chronic diarrhea
• Patients with neurological or psychiatric abnormalities including metastasis of the central nervous system that affect cognitive.
• Pregnant or lactated women (premenopausal women must give urine pregnancy test before enrollment).

Sponsors & Collaborators

• Peking University: lead

Study Sites (1)

Beijing Cancer Hospital, Peking University Cancer Hospital

Beijing, 100142, China

Location

Related Publications (14)

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MeSH Terms

Conditions

Esophageal Neoplasms

Interventions

S 1 (combination); Paclitaxel; tegafur-gimeracil-oteracil; TP protocol; Cisplatin; Fluorouracil

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Xiaodong Zhang, MD

  Beijing Cancer Hospital, Peking University Cancer Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Head of Medical Oncology VIP-II department

Study Record Dates

• First Submitted: October 4, 2012
• First Posted: October 11, 2012
• Study Start: August 1, 2012
• Primary Completion: March 1, 2017
• Study Completion: March 1, 2017
• Last Updated: April 7, 2017

Record last verified: 2017-04

Locations

CN (1)