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Study of Docetaxel or Vinorelbine Plus Cisplatin in Neoadjuvant Chemoradiotherapy for Esophageal Cancer

Primary Purpose

Esophageal Squamous Cell Carcinoma, Esophageal Cancer, Oesophageal Cancer

Status
Recruiting
Phase
Phase 3
Locations
China
Study Type
Interventional
Intervention
Docetaxel
Cisplatin
Radiation
Surgery
Vinorelbine
Cisplatin
Sponsored by
Sun Yat-sen University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Esophageal Squamous Cell Carcinoma

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Histologic diagnosis of squamous cell thoracic esophageal carcinoma of Stage T1-4aN1-3M0 or T4aN0M0, according to 7th edition of Union for International Cancer Control (UICC) staging system.
  2. Patients must not have received any prior anticancer therapy.
  3. More than 6 months of expected survival
  4. Age ranges from 18 to 70 years
  5. Absolute white blood cells count ≥4.0×109/L, neutrophil ≥1.5×109/L, platelets ≥100.0×109/L, hemoglobin ≥90g/L, and normal functions of liver and kidney.
  6. WHO performance status (PS) of 0-1
  7. Signed informed consent document on file

Exclusion Criteria:

  1. Patients have received any prior anticancer therapy
  2. Patients with advanced inoperable or metastatic esophageal carcinoma
  3. Patients with concomitant hemorrhagic disease
  4. Patients with other uncontrollable status that cannot tolerate surgery
  5. Pregnant or breast feeding
  6. Patients cannot signed the informed consent document because of psychological quality, family and social factors
  7. Patients with concomitant peripheral neuropathy, whose CTC status is 2 or even more
  8. Have a prior malignancy other than esophageal carcinoma, carcinoma in situ of the cervix, nonmelanoma skin cancer or cured early stage of prostate cancer
  9. Have a history of diabetes over 10 years and with poorly controlled blood sugar level
  10. patients with serious cardiac, respiratory, hepatic, renal, hematologic, immunological disease or cachexy, who cannot tolerate chemoradiotherapy or surgery

Sites / Locations

  • Sun Yat-sen University Cancer CenterRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

A (DP-RT)

B (NP-RT)

Arm Description

• Arm A consists of the concurrent chemoradiotherapy prior to surgery. The patient will receive 4 weeks of radiation therapy and 4 weekly cycles of chemotherapy. The radiation will generally commence on the 1st day of treatment and will run for 4 weeks. Chemotherapy is given by intravenous infusion on days 1, 8, 15, and 22. Interventions: Radiation: (44 Gy/20 fractions) Drug: Docetaxel Drug: Cisplatin

• Arm B consists of the concurrent chemoradiotherapy followed by surgery. The patient will receive 4 weeks of radiation therapy and 2 cycles of chemotherapy. The radiation will generally commence on the 1st day of treatment and will run for 4 weeks. Each cycle of chemotherapy lasts 21 days/3 weeks. The drugs include Vinorelbine and Cisplatin. Interventions: Radiation: (44 Gy/20 fractions) Drug: Vinorelbine Drug: Cisplatin

Outcomes

Primary Outcome Measures

Overall survival
Overall survival will be calculated from the date of randomisation and an event registered on the date of death from any cause. Patients lost to follow up, or those with no death recorded on the day the database is frozen, will be censored on the date of last follow up.
Toxicities of neo-adjuvant chemoradiotherapy
All symptoms of toxicity will be evaluated according to the Common Terminology Criteria for Adverse Events (CTCAE) Version. 3.0.

Secondary Outcome Measures

Disease free survival
Clinical response rate
R0 resection rate
Number of Participants who withdraw the treatment
Perioperative complication
Pathological complete response rate
Health Related Quality of Life

Full Information

First Posted
May 30, 2015
Last Updated
November 11, 2022
Sponsor
Sun Yat-sen University
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1. Study Identification

Unique Protocol Identification Number
NCT02465736
Brief Title
Study of Docetaxel or Vinorelbine Plus Cisplatin in Neoadjuvant Chemoradiotherapy for Esophageal Cancer
Official Title
A Phase III Clinical Trial of Docetaxel Plus Cisplatin Versus Vinorelbine Plus Cisplatin in Neoadjuvant Chemoradiotherapy for Locally Advanced Esophageal Squamous Cell Carcinoma
Study Type
Interventional

2. Study Status

Record Verification Date
November 2022
Overall Recruitment Status
Recruiting
Study Start Date
July 2015 (undefined)
Primary Completion Date
July 2023 (Anticipated)
Study Completion Date
July 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Sun Yat-sen University

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The primary objective is to compare docetaxel plus cisplatin (DP) versus vinorelbine plus cisplatin (NP) in neoadjuvant chemoradiotherapy, in terms of the overall survival and toxicity in patients with Stage IIB or III squamous cell esophageal carcinoma.
Detailed Description
Esophageal cancer (EC) is the eighth most common cancers in the world, with more than 456,000 new cases and 400,000 deaths occurred annually worldwide. Every year in China, no matter new cases or deaths account for more than half of the world. Besides, over 90% of Chinese patients have esophageal squamous cell carcinoma (ESCC). Preoperative chemoradiotherapy (CRT) followed by surgery can hopefully improve the survival of ESCC. The CROSS trial has demonstrated that preoperative chemoradiotherapy can significantly increase the overall survival of patients with EC compared with surgery alone. The therapeutic effects were also found in 84 ESCC cases enrolled in this trial. Previously, the investigators performed a phase III, randomized clinical trial (NCT01216527) to compare the overall survival of stage IIB-III ESCC patients treated with or without neoadjuvant CRT, in which vinorelbine plus cisplatin was used as chemotherapy regime. The enrollment was completed in 2014. The outcomes will hopefully prove the survival benefit of neoadjuvant CRT to ESCC. However, the investigators also observed that some patients suffer from the toxic response of neoadjuvant therapy, such as myelosuppression (45.2%), pulmonary toxicity (42.9%), and esophagitis (59.5%). The toxicity caused by CRT will decrease the patient compliance; moreover increase the perioperative complications and deaths, which may totally offset the survival benefit. Therefore, it is important to improve chemoradiotherapy effect and reduce toxicity, so as to achieve better survival in ESCC patients. Docetaxel draws increasing attentions with its high effective rate and low toxicity. Several Phase II clinical trials and retrospective studies suggested that docetaxel showed better survival benefits in both monotherapy and combined-therapy in EC patients. Therefore, the investigators intended to conduct a phase III, randomized clinical trial to further explore whether docetaxel plus cisplatin would be an effective therapy with lower toxicity. The investigators are to carry out a phased III clinical trial to compare the effect and toxicity of docetaxel plus cisplatin with vinorelbine plus cisplatin in neoadjuvant chemoradiotherapy for esophageal squamous cell carcinoma.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Esophageal Squamous Cell Carcinoma, Esophageal Cancer, Oesophageal Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
610 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
A (DP-RT)
Arm Type
Experimental
Arm Description
• Arm A consists of the concurrent chemoradiotherapy prior to surgery. The patient will receive 4 weeks of radiation therapy and 4 weekly cycles of chemotherapy. The radiation will generally commence on the 1st day of treatment and will run for 4 weeks. Chemotherapy is given by intravenous infusion on days 1, 8, 15, and 22. Interventions: Radiation: (44 Gy/20 fractions) Drug: Docetaxel Drug: Cisplatin
Arm Title
B (NP-RT)
Arm Type
Experimental
Arm Description
• Arm B consists of the concurrent chemoradiotherapy followed by surgery. The patient will receive 4 weeks of radiation therapy and 2 cycles of chemotherapy. The radiation will generally commence on the 1st day of treatment and will run for 4 weeks. Each cycle of chemotherapy lasts 21 days/3 weeks. The drugs include Vinorelbine and Cisplatin. Interventions: Radiation: (44 Gy/20 fractions) Drug: Vinorelbine Drug: Cisplatin
Intervention Type
Drug
Intervention Name(s)
Docetaxel
Other Intervention Name(s)
Docetaxel in Arm A
Intervention Description
25mg/ m2 Docetaxel dose administered on days 1, 8, 15, and 22.
Intervention Type
Drug
Intervention Name(s)
Cisplatin
Other Intervention Name(s)
Cisplatin in Arm A
Intervention Description
25mg/ m2 on days 1, 8, 15 and 22.
Intervention Type
Radiation
Intervention Name(s)
Radiation
Other Intervention Name(s)
IMRT
Intervention Description
Patient will receive 4 weeks of radiation therapy (44 Gy/20 fractions).
Intervention Type
Procedure
Intervention Name(s)
Surgery
Other Intervention Name(s)
Esophagectomy
Intervention Description
McKeown esophagectomy, Ivor Lewis esophagectomy or minimally invasive esophagectomy will be performed 4-8 weeks after chemoradiotherapy. Two-field lymphadenectomy with total mediastinal lymph node dissection is performed during surgery.
Intervention Type
Drug
Intervention Name(s)
Vinorelbine
Other Intervention Name(s)
Vinorelbine in Arm B
Intervention Description
25mg/ m2 on days 1, 8 of each cycle (i.e. every 21 days).
Intervention Type
Drug
Intervention Name(s)
Cisplatin
Other Intervention Name(s)
Cisplatin in Arm B
Intervention Description
75mg/ m2 on day 1 of each cycle only (i.e. every 21 days).
Primary Outcome Measure Information:
Title
Overall survival
Description
Overall survival will be calculated from the date of randomisation and an event registered on the date of death from any cause. Patients lost to follow up, or those with no death recorded on the day the database is frozen, will be censored on the date of last follow up.
Time Frame
At end of trial- up to 3 years in follow up
Title
Toxicities of neo-adjuvant chemoradiotherapy
Description
All symptoms of toxicity will be evaluated according to the Common Terminology Criteria for Adverse Events (CTCAE) Version. 3.0.
Time Frame
Within the first 56 days after the start of chemoradiotherapy
Secondary Outcome Measure Information:
Title
Disease free survival
Time Frame
At end of trial- up to 3 years in follow up
Title
Clinical response rate
Time Frame
4-6 weeks after completion of chemoradiotherapy
Title
R0 resection rate
Time Frame
One week after the operation
Title
Number of Participants who withdraw the treatment
Time Frame
Within the first 84 days after the start of chemoradiotherapy
Title
Perioperative complication
Time Frame
Within the first 90 days after the start of surgery
Title
Pathological complete response rate
Time Frame
One week after the operation
Title
Health Related Quality of Life
Time Frame
Within the first 84 days after the start of chemoradiotherapy

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Histologic diagnosis of squamous cell thoracic esophageal carcinoma of Stage T1-4aN1-3M0 or T4aN0M0, according to 7th edition of Union for International Cancer Control (UICC) staging system. Patients must not have received any prior anticancer therapy. More than 6 months of expected survival Age ranges from 18 to 70 years Absolute white blood cells count ≥4.0×109/L, neutrophil ≥1.5×109/L, platelets ≥100.0×109/L, hemoglobin ≥90g/L, and normal functions of liver and kidney. WHO performance status (PS) of 0-1 Signed informed consent document on file Exclusion Criteria: Patients have received any prior anticancer therapy Patients with advanced inoperable or metastatic esophageal carcinoma Patients with concomitant hemorrhagic disease Patients with other uncontrollable status that cannot tolerate surgery Pregnant or breast feeding Patients cannot signed the informed consent document because of psychological quality, family and social factors Patients with concomitant peripheral neuropathy, whose CTC status is 2 or even more Have a prior malignancy other than esophageal carcinoma, carcinoma in situ of the cervix, nonmelanoma skin cancer or cured early stage of prostate cancer Have a history of diabetes over 10 years and with poorly controlled blood sugar level patients with serious cardiac, respiratory, hepatic, renal, hematologic, immunological disease or cachexy, who cannot tolerate chemoradiotherapy or surgery
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Hong Yang, Ph.D., M.D.
Email
yanghong@sysucc.org.cn
First Name & Middle Initial & Last Name or Official Title & Degree
Ting Lin, Study nurse
Phone
86-20-87343628
Email
linting@sysucc.org.cn
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Hong Yang, Ph.D., M.D.
Organizational Affiliation
Sun Yat-sen University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Sun Yat-sen University Cancer Center
City
Guangzhou
State/Province
Guangdong
ZIP/Postal Code
510060
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Hong Yang, MD, PhD
Phone
+86+13560405144
Email
yanghong@sysucc.org.cn

12. IPD Sharing Statement

Plan to Share IPD
No
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Study of Docetaxel or Vinorelbine Plus Cisplatin in Neoadjuvant Chemoradiotherapy for Esophageal Cancer

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