Clinical trial NCT02465736: Study of Docetaxel or Vinorelbine Plus Cisplatin in Neoadjuvant Chemoradiotherapy for Esophageal Cancer (NEOCRTEC308)
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 (NEOCRTEC308)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Esophageal Squamous Cell Carcinoma
Esophageal Cancer
Oesophageal Cancer
Lead sponsor: Sun Yat-sen University
Sponsor class: OTHER
First posted: 2015-06-08
Enrollment: 610
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Overall survival
timeFrame: At end of trial- up to 3 years in follow up
measure: Toxicities of neo-adjuvant chemoradiotherapy
timeFrame: Within the first 56 days after the start of chemoradiotherapy
Secondary outcomes:
measure: Disease free survival
timeFrame: At end of trial- up to 3 years in follow up
measure: Clinical response rate
timeFrame: 4-6 weeks after completion of chemoradiotherapy
measure: R0 resection rate
timeFrame: One week after the operation
measure: Number of Participants who withdraw the treatment
timeFrame: Within the first 84 days after the start of chemoradiotherapy
measure: Perioperative complication
timeFrame: Within the first 90 days after the start of surgery
measure: Pathological complete response rate
timeFrame: One week after the operation
measure: Health Related Quality of Life
timeFrame: Within the first 84 days after the start of chemoradiotherapy
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Sun Yat-sen University Cancer Center
state: Guangdong
Study officials:
affiliation: Sun Yat-sen University
name: Hong Yang, Ph.D., M.D.
role: PRINCIPAL_INVESTIGATOR
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