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

Sponsor

Sun Yat-sen University (Other)

Overall Status

Recruiting

CT.gov ID

NCT02465736

Collaborator

(none)

610

Enrollment

Location

Arms

Duration (Months)

6.4

Patients Per Site Per Month

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Esophageal Squamous Cell Carcinoma Esophageal Cancer Oesophageal Cancer	Drug: Docetaxel Drug: Cisplatin Radiation: Radiation Procedure: Surgery Drug: Vinorelbine Drug: Cisplatin	Phase 3

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

610 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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 Start Date :

Jul 1, 2015

Anticipated Primary Completion Date :

Jul 1, 2023

Anticipated Study Completion Date :

Jul 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: A (DP-RT) • 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	Drug: Docetaxel 25mg/ m2 Docetaxel dose administered on days 1, 8, 15, and 22. Other Names: Docetaxel in Arm A Drug: Cisplatin 25mg/ m2 on days 1, 8, 15 and 22. Other Names: Cisplatin in Arm A Radiation: Radiation Patient will receive 4 weeks of radiation therapy (44 Gy/20 fractions). Other Names: IMRT Procedure: Surgery 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. Other Names: Esophagectomy
Experimental: B (NP-RT) • 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	Radiation: Radiation Patient will receive 4 weeks of radiation therapy (44 Gy/20 fractions). Other Names: IMRT Procedure: Surgery 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. Other Names: Esophagectomy Drug: Vinorelbine 25mg/ m2 on days 1, 8 of each cycle (i.e. every 21 days). Other Names: Vinorelbine in Arm B Drug: Cisplatin 75mg/ m2 on day 1 of each cycle only (i.e. every 21 days). Other Names: Cisplatin in Arm B

Arm

Intervention/Treatment

Experimental: A (DP-RT)

• 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

Drug: Docetaxel

25mg/ m2 Docetaxel dose administered on days 1, 8, 15, and 22.

Other Names:

Docetaxel in Arm A

Drug: Cisplatin

25mg/ m2 on days 1, 8, 15 and 22.

Other Names:

Cisplatin in Arm A

Radiation: Radiation

Patient will receive 4 weeks of radiation therapy (44 Gy/20 fractions).

Other Names:

IMRT

Procedure: Surgery

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.

Other Names:

Esophagectomy

Experimental: B (NP-RT)

• 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

Radiation: Radiation

Patient will receive 4 weeks of radiation therapy (44 Gy/20 fractions).

Other Names:

IMRT

Procedure: Surgery

Other Names:

Esophagectomy

Drug: Vinorelbine

25mg/ m2 on days 1, 8 of each cycle (i.e. every 21 days).

Other Names:

Vinorelbine in Arm B

Drug: Cisplatin

75mg/ m2 on day 1 of each cycle only (i.e. every 21 days).

Other Names:

Cisplatin in Arm B

Outcome Measures

Primary Outcome Measures

Overall survival [At end of trial- up to 3 years in follow up]
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 [Within the first 56 days after the start of 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 [At end of trial- up to 3 years in follow up]
Clinical response rate [4-6 weeks after completion of chemoradiotherapy]
R0 resection rate [One week after the operation]
Number of Participants who withdraw the treatment [Within the first 84 days after the start of chemoradiotherapy]
Perioperative complication [Within the first 90 days after the start of surgery]
Pathological complete response rate [One week after the operation]
Health Related Quality of Life [Within the first 84 days after the start of chemoradiotherapy]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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