Study of Docetaxel or Vinorelbine Plus Cisplatin in Neoadjuvant Chemoradiotherapy for Esophageal Cancer (NEOCRTEC308)

Sun Yat-sen University

Status and phase: Active, not recruiting; Phase 3

Conditions: Oesophageal Cancer; Esophageal Cancer; Esophageal Squamous Cell Carcinoma

Treatments: Drug: Cisplatin; Drug: Vinorelbine; Radiation: Radiation; Procedure: Surgery; Drug: Docetaxel

Study type: Interventional

Funder types: Other

Identifiers

NCT02465736

NEOCRTEC-2.0

Details and patient eligibility

About

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.

Full 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.

Enrollment: 610 estimated patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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610 participants in 2 patient groups

A (DP-RT)

Experimental group

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

Treatment:

Drug: Docetaxel

Procedure: Surgery

Radiation: Radiation

Drug: Cisplatin

Drug: Cisplatin

B (NP-RT)

Experimental group

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

Treatment:

Procedure: Surgery

Radiation: Radiation

Drug: Vinorelbine

Drug: Cisplatin

Drug: Cisplatin