Phase III Study of Neo-adjuvant Chemoradiotherapy Followed by Surgery for Squamous Cell Esophageal Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified December 2013 by Sun Yat-sen University
Sponsor:
Collaborators:
Cancer Hospital of Shantou University
Shanghai Chest Hospital
Fudan University
Zhejiang Cancer Hospital
Taizhou Hospital
The Second People's Hospital of Sichuan
Tianjin Medical University Cancer Institute and Hospital
Information provided by (Responsible Party):
Jianhua Fu, Sun Yat-sen University
ClinicalTrials.gov Identifier:
NCT01216527
First received: October 6, 2010
Last updated: December 15, 2013
Last verified: December 2013
  Purpose

The primary objective is to compare neo-adjuvant chemoradiotherapy followed by surgery versus surgery, in terms of the overall survival time (OS) in patients with Stage IIB or III squamous cell esophageal carcinoma.


Condition Intervention Phase
Squamous Cell Esophageal Carcinoma
Procedure: Neo-adjuvant Chemoradiotherapy followed by Surgery
Procedure: surgery
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase III, Multicenter Randomized Controlled Study of Neo-adjuvant Chemoradiotherapy Followed by Surgery Versus Surgery for Locally Advanced Squamous Cell Esophageal Carcinoma

Resource links provided by NLM:


Further study details as provided by Sun Yat-sen University:

Primary Outcome Measures:
  • Overall survival rate [ Time Frame: 3 and 5 years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • toxicities of neo-adjuvant chemoradiotherapy [ Time Frame: 56 days ] [ Designated as safety issue: Yes ]
    Evaluate the toxicities of neo-adjuvant chemoradiotherapy,according to National Cancer Institute Common Terminology Criteria for Adverse Event,Version 3.0(CTC AE3.0).

  • assessment in perioperation [ Time Frame: perioperative period ] [ Designated as safety issue: Yes ]
    Removal rate, Time of operation, Quantity of bleeding, Thoracic Drainage, Days of Hospitalization, Rate of Operative Complication, Mortality of perioperation,

  • efficacy of neo-adjuvant chemoradiotherapy [ Time Frame: 4 weeks after completion of radiotherapy ] [ Designated as safety issue: No ]
    Criteria:Response Evaluation Criteria in Solid Tumors,RECIST

  • Disease free survival rate [ Time Frame: 5 years ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 430
Study Start Date: June 2007
Estimated Study Completion Date: December 2019
Estimated Primary Completion Date: December 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: experimental group
Neo-adjuvant Chemoradiotherapy followed by Surgery
Procedure: Neo-adjuvant Chemoradiotherapy followed by Surgery
  1. Radiotherapy combined with concomitant chemotherapy:

    Radiotherapy Program:External radiation with a total dose of 40.0Gy is given in 20 fractions of 2.0Gy,5 fractions a week.

    neo-chemotherapy program: Vinorelbine 25mg/m2, IV (in the vein) on day 1 and day 8 of each 21 day cycle. Cisplatin 75mg/m2,IV DRIP on day 1 of each 21 day cycle;or Cisplatin 25mg/m2,IV DRIP on day 1 to day 4 of each 21 day cycle.

    Number of cycles:two

  2. surgery:Mckeown Modification Surgery and total two-field lymphadenectomy
Active Comparator: control group
only Surgery
Procedure: surgery
two field lymphadenectomy

Detailed Description:

Esophageal cancer (EC) is the eighth most common cancers in the world, with more than 480,000 new cases and 400,000 deaths occurred annually worldwide. In China, every year, 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).

Surgery is the main treatment of this disease, but the prognosis of patients with locally advanced esophageal cancer is rather poor. As a result of surgery alone, the 5-year survival rate of about 25% has not changed significantly in several decades.

Preoperative chemoradiotherapy followed by surgery seems to hopefully improve the survival of EC. Nevertheless, the results of different studies were inconsistent. Recently, the CROSS trial has demonstrated that preoperative chemoradiotherapy can significantly increased the overall survival of patients with EC compared with surgery alone. It should be noticed that only 84 cases(23%) of ESCC were enrolled in this trial with potential minimal follow-up of 2 years, which may be not perfect to evaluate the effect of this combined therapy for this tumor type.

Up till now, vinorelbine has no indications for esophageal cancer, although, some studied have reported its effect and feasibility to the therapy of EC. Vinorelbine has similar mechanism with paclitaxel and docetaxel, which are recommended for the chemotherapy of EC by NCCN. They are all classified as antimicrotubule agents, which cause mitotic arrest and eventual cell death through inhibition of microtubule dynamics. In comparison with the taxanes, vinorelbine has obvious advantage of few cardiac toxicity. This should be beneficial to prevent cardiac side effects of chemoradiotherapy, especially for the middle or lower thoracic EC, which account for over 70% of thoracic EC in China. For this group of patients, radiotherapy can hardly avoid cardiac toxicity.

Based on our preliminary study, we have demonstrated the validity and safety of vinorelbine and cisplatin-based neoadjuvant chemoradiotherapy.

We are to carry out a phased III clinical trial to investigate the effect of this multidisciplinary therapy for the overall survival of patients with locally advanced ESCC.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Histologic diagnosis of squamous cell thoracic esophageal carcinoma of Stage IIB or III, which is potentially resectable.
  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. Karnofsky performance status (KPS) of 90 or more.
  7. Signed informed consent document on file.

Exclusion Criteria:

  1. Patients are diagnosed or suspected to be allergic to cisplatin or vinorelbine.
  2. Patients with concomitant hemorrhagic disease.
  3. Pregnant or breast feeding.
  4. Inability to use gastric conduit after esophagectomy because of a prior surgery.
  5. Patients with concomitant peripheral neuropathy, whose CTC status is 2 or even more.
  6. Have a prior malignancy other than esophageal carcinoma, carcinoma in situ of the cervix, nonmelanoma skin cancer or cured early stage of prostate cancer.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01216527

Contacts
Contact: Jian-hua Fu, professor 86-20-87343638 fujh@sysucc.org.cn
Contact: Ting Lin, study nurse 86-20-87343628 linting@sysucc.org.cn

Locations
China, Guangdong
Sun Yat-sen Uniersity Cancer Center Recruiting
GuangZhou, Guangdong, China, 510060
Contact: Jian-hua Fu, Professor    86-20-87343638    fujh@sysucc.org.cn   
Contact: Kong-jia Luo, doctor    86-20-87343258    luokj@sysucc.org.cn   
Principal Investigator: Jian-hua Fu, Professor         
Cancer Hospital of Shantou University Medical College Recruiting
Shantou, Guangdong, China, 515000
Contact: Yu-ping Chen, professor       stchenyp@hotmail.com   
Principal Investigator: Yu-ping Chen, Professor         
Sponsors and Collaborators
Sun Yat-sen University
Cancer Hospital of Shantou University
Shanghai Chest Hospital
Fudan University
Zhejiang Cancer Hospital
Taizhou Hospital
The Second People's Hospital of Sichuan
Tianjin Medical University Cancer Institute and Hospital
Investigators
Principal Investigator: Jian-hua Fu, Professor Sun Yat-sen University
  More Information

No publications provided

Responsible Party: Jianhua Fu, Professor, Sun Yat-sen University
ClinicalTrials.gov Identifier: NCT01216527     History of Changes
Other Study ID Numbers: 2007048
Study First Received: October 6, 2010
Last Updated: December 15, 2013
Health Authority: China: Ethics Committee

Keywords provided by Sun Yat-sen University:
Stage IIB or III squamous cell esophageal carcinoma.

Additional relevant MeSH terms:
Carcinoma
Esophageal Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Head and Neck Neoplasms
Digestive System Diseases
Esophageal Diseases
Gastrointestinal Diseases

ClinicalTrials.gov processed this record on September 30, 2014