Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT03005314 |
| Other study ID # |
2016YFC0106005 |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
N/A
|
| First received |
August 4, 2016 |
| Last updated |
January 17, 2018 |
| Start date |
August 2016 |
| Est. completion date |
December 2019 |
Study information
| Verified date |
January 2018 |
| Source |
The Second Hospital of Shandong University |
| Contact |
Yunpeng Zhao, doctor |
| Phone |
+8618766188692 |
| Email |
zyp_baggio[@]163.com |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Esophageal carcinoma is a common digestive system tumor, with number of deaths ranking No. 4
in malignant tumors. Esophageal squamous cell carcinoma in stage Ⅱ, III is the most common in
China. The esophageal cancer during these stages is no longer localized lesions, and cancer
will be transferred to other organs of the body through blood transmission, leading to tumor
metastasis, which is the main cause of the patients' death. The tumor cells invade the
surrounding tissues of primary tumor cells and enter the blood and lymphatic system, thus the
circulating tumor cells (CTC) is formed and transported to a distal tissue, then effusing,
adapting to the new microenvironment and finally forming metastases through the process of
seeding, proliferation and colonization.
Recently, the controversy of surgical treatment of esophageal carcinoma is concentrated on
the neoadjuvant therapy during perioperative period. NCCN guideline of 2015 recommended that
patients with esophageal squamous cell carcinoma in T1b, N + and T2-T4a, N0-N + may consider
preoperative neoadjuvant therapy, but its supporting literature (David Cunningham 2006, Marc
Ychou 2011 and P. van Hagen, 2013) includes patients with pathology of the type
adenocarcinoma. The esophageal cancer treatment guidelines of Japan 2015 adopted the opinion
of NCCN Guidelines, and recommended neoadjuvant chemotherapy and radical surgery as the
standard treatment for stage II and III esophageal cancer patients based on the results of
randomized controlled clinical trial JCOG9907. However, the guidelines also pointed out that
the role of neoadjuvant chemotherapy for resectable T1-3N0-1M0 cancers remains unclear
according to the results of some meta-analysis.
The investigators choose the detection of peripheral venous blood CTCs and the disease-free
survival as the main index, to compare the treatment effect of patients, those received
neoadjuvant therapy, surgery and those received directly surgery, postoperative chemotherapy
with esophageal squamous cell carcinoma in stage Ⅱ, III by means of evidence-based medicine;
Define the indication of neoadjuvant chemotherapy in the treatment of esophageal squamous
cell carcinoma in stage Ⅱ, III; Draft the solution to evaluate the treatment effect of
neoadjuvant chemotherapy to esophageal cancer in stage Ⅱ, III, and the indication of
neoadjuvant chemotherapy by test the peripheral venous blood CTCs and join the Chinese
clinical guideline.
Description:
Background Esophageal carcinoma is a common digestive system tumor, with number of deaths
ranking No. 4 in malignant tumors. Surgery is the preferred method of treatment for
esophageal cancer, but the local recurrence rate is as high as between 40% and 60%, and
5-year overall survival is only about 30%. Most of esophageal cancers are found in the middle
and late stage, losing the chance of operation. Esophageal squamous cell carcinoma in stage
Ⅱ, III is the most common in China. The esophageal cancer during these stages is no longer
localized lesions, and cancer will be transferred to other organs of the body through blood
transmission, leading to tumor metastasis, which is the main cause of the patients' death.
The tumor cells invade the surrounding tissues of primary tumor cells and enter the blood and
lymphatic system, thus the circulating tumor cells (CTC) is formed and transported to a
distal tissue, then effusing, adapting to the new microenvironment and finally forming
metastases through the process of seeding, proliferation and colonization. In recent years,
as liquid pathology, CTCs are used for several studies of tumor, including the auxiliary
diagnosis, recurrence and metastasis detection, prognosis, individualized treatment, medical
screening, development of new targeted cancer therapy drugs, searching for a new target for
cancer therapy, exploring the mechanism of drug resistance, etc.
Recently, the controversy of surgical treatment of esophageal carcinoma is concentrated on
the neoadjuvant therapy during perioperative period. Neoadjuvant therapy has been widely
studied in recent years. Compared to the postoperative radiochemotherapy,the preoperative
chemotherapy is less toxic and better tolerated. Pure radiotherapy could only work on the
local tumor, yet without lethal effect towards micrometastases and CTCs. Studies have shown
that neoadjuvant radiotherapy can only improve the resection rate, but could not prolong the
patient's survival; the advantages of neoadjuvant chemotherapy include: 1. lower tumor stage,
reduce tumor volume , and increase the resection rate; 2. control and treat the tiny
metastasis, reduce the recurrence rate; 3. chemotherapeutic drugs can reach to tumor issues
with sufficient amount , through the undamaged blood supply system; 4. assess the
chemosensitivity of drug in body to guide postoperative treatment.
NCCN guideline of 2015 recommended that patients with esophageal squamous cell carcinoma in
T1b, N + and T2-T4a, N0-N + may consider preoperative neoadjuvant therapy, but its supporting
literature (David Cunningham 2006, Marc Ychou 2011 and P. van Hagen, 2013) includes patients
with pathology of the type adenocarcinoma. The esophageal cancer treatment guidelines of
Japan 2015 adopted the opinion of NCCN Guidelines, and recommended neoadjuvant chemotherapy
and radical surgery as the standard treatment for stage II and III esophageal cancer patients
based on the results of randomized controlled clinical trial JCOG9907. However, the
guidelines also pointed out that the role of neoadjuvant chemotherapy for resectable
T1-3N0-1M0 cancers remains unclear according to the results of some meta-analysis. But at
least for the present studies, compared to direct surgery group, the patients received
neoadjuvant therapy did not show inferior effect at aspects such as radical surgery,
postoperative complications, disease-free survival and overall survival.
The effect and necessity of neoadjuvant chemotherapy to esophageal squamous cell carcinoma
patients in stage Ⅱ, Ⅲ, and its influence to disease-free survival still lack authoritative
evidence-based medical support, is a clinical urgency need to be solved.
Research objectives Choose the detection of peripheral venous blood CTCs and the disease-free
survival as the main index, to compare the treatment effect of patients, those received
neoadjuvant therapy, surgery and those received directly surgery, postoperative chemotherapy
with esophageal squamous cell carcinoma in stage Ⅱ, III by means of evidence-based medicine;
Define the indication of neoadjuvant chemotherapy in the treatment of esophageal squamous
cell carcinoma in stage Ⅱ, III; Draft the solution to evaluate the treatment effect of
neoadjuvant chemotherapy to esophageal cancer in stage Ⅱ, III, and the indication of
neoadjuvant chemotherapy by test the peripheral venous blood CTCs and join the Chinese
clinical guideline.
Main research content:
Design dual-center (Second Hospital of Shandong University and Shandong Cancer Hospital
Affiliated to Shandong University) prospective clinical contrast trials by selecting the
preoperative patients with esophageal squamous cell carcinoma in clinical stage Ⅱ, III.
Complete the work of patients screening, informed consent, preoperative preparation, surgery,
neoadjuvant chemotherapy and follow-up visits under the guide of Standardized treatment
program. Detect the CTCs by extract the peripheral venous blood at the time of the day before
initial treatment (neoadjuvant chemotherapy or surgery), one week after surgery and the
follow-up visits of 3 months, 6 months, 1 year, 2years after surgery. The main evaluation
index of the study is the change of CTCs in peripheral blood and the survival period of
disease-free of patients, with secondary evaluation index including the surgery effect,
pathology, recurrence rate of the patients, long-term survival as well as other prognostic
indicators. Assess the guidance of CTCs detection towards neoadjuvant chemotherapy in the
treatment of esophageal squamous carcinoma in stage Ⅱ, III.
