A Phase III Study of Comparing Paclitaxel Plus 5-Fluorouracil Versus Cisplatin Plus 5-Fluorouracil in Chemoradiotherapy for Locally Advanced Esophageal Carcinoma

Sponsor

Fudan University (Other)

Overall Status

Completed

CT.gov ID

NCT01591135

Collaborator

Jiangsu Cancer Institute & Hospital (Other), First Affiliated Hospital of Zhejiang University (Other), The First Affiliated Hospital of Xiamen University (Other), Fujian Cancer Hospital (Other), Affiliated Hospital of Jiangnan University (Other)

436

Enrollment

Location

Arms

Actual Duration (Months)

5.7

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The primary objective of this trial is to study whether paclitaxel plus 5-fluorouracil has better overall survival than cisplatin plus 5-fluorouracil in chemoradiotherapy for patients with locally advanced esophageal squamous cell carcinoma. 436 patients will be recruited into this study.

Condition or Disease	Intervention/Treatment	Phase
Esophageal Squamous Cell Carcinoma	Drug: Paclitaxel plus 5-fluorouracil Drug: Cisplatin plus 5-fluorouracil Radiation: Radiation therapy Radiation: Radiation therapy	Phase 3

Detailed Description

Locally advanced esophageal squamous cell carcinoma. T2-4N0-1M0-1a,TxN1M0-1a，TxNxM1a （according to AJCC2002）

Scheme:

Eligible recurrent patients with esophageal cancer will first be stratified by nodal staging (N0 or N1), then randomized to 2 arms at 1:1 ratio.

Arm Cisplatin:

Chemoradiotherapy with cisplatin and 5-fluorouracil for 4 cycles.

Arm Paclitaxel:

Chemoradiotherapy with weekly paclitaxel and 5-fluorouracil for 5 weeks followed by adjuvant chemotherapy for 2 cycles.

Study Design

Study Type:

Interventional

Actual Enrollment :

436 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase III Randomized Clinical Trial of Comparing Paclitaxel Plus 5-Fluorouracil Versus Cisplatin Plus 5-Fluorouracil in Chemoradiotherapy for Patients With Locally Advanced Esophageal Squamous Cell Carcinoma

Actual Study Start Date :

Apr 1, 2012

Actual Primary Completion Date :

Aug 1, 2018

Actual Study Completion Date :

Aug 1, 2018

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Cisplatin Chemoradiotherapy with cisplatin and 5-fluorouracil for 2 cycles followed by adjuvant chemotherapy for 2 cycles.	Drug: Cisplatin plus 5-fluorouracil cisplatin 25 mg/m2/d, d1-3, once every 4 weeks for 4 cycles (week 1, week 5, week 9 and week 13); 5-FU 600 mg/m2/d, d1-3, continuously infusion for 72 hrs,once every 4 weeks for 4 cycles (week 1, week 5, week 9 and week 13). Radiation: Radiation therapy A total dose of 61.2 Gy will be delivered in 34 fractions at 1.8 Gy/fraction, 5 fractions per week in 6.8 weeks.
Experimental: Paclitaxel Patients randomized in Arm B will receive chemoradiation with weekly paclitaxel and 5-fluorouracil for 5 weeks followed by adjuvant chemotherapy with paclitaxel and 5-fluorouracil for 2 cycles.	Drug: Paclitaxel plus 5-fluorouracil 5-ﬂuorouracil 300 mg/m2, d1-4, continuous infusion for 96 hours and paclitaxel 50 mg/m2 over 3 hours, d1 (week 1, week 2, week 3, week 4 and week 5); 5-ﬂuorouracil 600 mg/m2/d d1-3 and paclitaxel 175 mg/m2 d1(week 9 and week 13). Radiation: Radiation therapy A total dose of 61.2 Gy will be delivered in 34 fractions at 1.8 Gy/fraction, 5 fractions per week in 6.8 weeks.

Arm

Intervention/Treatment

Active Comparator: Cisplatin

Chemoradiotherapy with cisplatin and 5-fluorouracil for 2 cycles followed by adjuvant chemotherapy for 2 cycles.

Drug: Cisplatin plus 5-fluorouracil

cisplatin 25 mg/m2/d, d1-3, once every 4 weeks for 4 cycles (week 1, week 5, week 9 and week 13); 5-FU 600 mg/m2/d, d1-3, continuously infusion for 72 hrs,once every 4 weeks for 4 cycles (week 1, week 5, week 9 and week 13).

Radiation: Radiation therapy

A total dose of 61.2 Gy will be delivered in 34 fractions at 1.8 Gy/fraction, 5 fractions per week in 6.8 weeks.

Experimental: Paclitaxel

Patients randomized in Arm B will receive chemoradiation with weekly paclitaxel and 5-fluorouracil for 5 weeks followed by adjuvant chemotherapy with paclitaxel and 5-fluorouracil for 2 cycles.

Drug: Paclitaxel plus 5-fluorouracil

5-ﬂuorouracil 300 mg/m2, d1-4, continuous infusion for 96 hours and paclitaxel 50 mg/m2 over 3 hours, d1 (week 1, week 2, week 3, week 4 and week 5); 5-ﬂuorouracil 600 mg/m2/d d1-3 and paclitaxel 175 mg/m2 d1(week 9 and week 13).

Radiation: Radiation therapy

A total dose of 61.2 Gy will be delivered in 34 fractions at 1.8 Gy/fraction, 5 fractions per week in 6.8 weeks.

Outcome Measures

Primary Outcome Measures

3-yr overall survival [3 years]

Secondary Outcome Measures

Disease progression-free survival [3 years]
Local progression-free survival [3 years]
Number and grade of Participants with Adverse Events [6 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Joined the study voluntarily and signed informed consent form;
Age 18-75
Both genders
Esophageal squamous cell carcinoma confirmed by pathology
Local advanced esophageal squamous cell carcinoma (T2N0M0-TxNxM1a, AJCC 2002)
No radiotherapy, chemotherapy or other treatments prior to enrollment
PS ECOG 0-2
Life expectancy of more than 3 months
Hemoglobin（Hb）≥9 g/dL
WBC≥3x109/L, Neutrophils (ANC )≥1.5x109/L
platelet count (Pt) ≥100x 109/L
Hepatic function: ALAT and ASAT < 2.5 x ULN, TBIL<1.5 x ULN
Renal function: creatinine < 1.5 x ULN
No immuno-deficiency
Use of an effective contraceptive for adults to prevent pregnancy.

Exclusion Criteria:

Complete esophageal obstruction
Deep esophageal ulcer
Esophageal perforation
Haematemesis
After surgery, exploratory thoracotomy, radiotherapy, chemotherapy, or targeting therapy
Other malignant tumors, except for skin basal cell carcinoma, or cervical carcinoma in situ, who survived with no evidence disease for over 3 years
Participation in other interventional clinical trials within 30 days
Pregnant or breast-feeding women or people during the birth-period who refused to take contraceptives
Drug addiction
Alcoholism or AIDS
Uncontrolled seizures or psychiatric diseases, loss of control over their own behavior
Patient who has metastasis such as lung, liver metastasis