Phase II Study of Neo-adjuvant Chemoradiotherapy for Squamous Cell Esophageal Cancer

Surgery Clinical Trial

Official title:

Phase II Study of Optimum Design of Neo-adjuvant Chemoradiotherapy Followed by Surgery for Squamous Cell Esophageal Cancer

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02938195
• Other study ID #: SCHEC001
• Status: Recruiting
• Phase: Phase 2
• First received: October 15, 2016
• Last updated: October 18, 2016
• Start date: January 2016
• Est. completion date: January 2018

Study information

• Verified date: October 2016
• Source: Shanghai Chest Hospital
• Contact: Jun Liu, Doctor
• Phone: +862122200000
• Email: drjunliu[@]qq.com
• Is FDA regulated: No
• Health authority: China: Shanghai Municipal Commission of Health and Family Planning
• Study type: Interventional

Clinical Trial Summary

The investigators designed a new preoperative chemoradiotherapy regimen to focus on the most important radiation area and hope to reduce the radiation volume and try to reduce the postoperative mortality and treatment-related mortality.

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, either new cases or deaths account for more than half of the world. Morever, 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.

Neo-adjuvant chemoradiotherapy followed by surgery seems hopeful to improve the survival of EC. Recently, the CROSS trial has demonstrated that preoperative chemoradiotherapy can significantly increased the overall survival of patients with EC compared with surgery alone. However,a recent meta-analysis has indicated that an increased risk of postoperative mortality and treatment-related mortality was apparent in ESCC with the treatment of neo-adjuvant chemoradiotherapy.

Compare to surgery alone,the advantage of neoadjuvant chemoradiotherapy is reflected in the significantly higher percentage of R0 resections and higher rate of pathological complete response.

Thus,the investigators designed a new preoperative chemoradiotherapy regimen to focus on the most important radiation area and hope to reduce the radiation volume and try to reduce the postoperative mortality and treatment-related mortality.

Radiotherapy:Patients will be conducted CT simulation, and three-dimensional radiation therapy or Intensity-modulated radiation therapy was performed. 1.8Gy/fraction, 5 fractions a week, with a total dose of 4140cgy will be delivered for all patients by 6-MV-X-ray of linear accelerator.

Chemotherapy:Patients will be concurrently administered with irradiation every 4 weeks with PF regimen (cis-platinum of 25 mg/m2/d, d1-3; 5-fluorouracil of 500mg/m2/d, d1-4) for 2 cycles.

Surgery:Patients will receive operation 4-8 weeks after chemoradiotherapy.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 50
• Est. completion date: January 2018
• Est. primary completion date: January 2018
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

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 5-Fu.

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.

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma, Squamous Cell
• Chemoradiation
• Esophageal Cancer
• Esophageal Neoplasms
• Surgery

Intervention

Radiation:
• radiotherapy
The clinical target volume of radiotherapy only includes the visible tumor and lymph nodes and the investigators wouldn't do any prophylactic radiation treatment.

Procedure:
• Surgery
Surgery would be done 4-8 weeks after neoadjuvant chemoradiotherapy.

Locations

Country	Name	City	State
China	Shanghai Chest Hospital	Shanghai	Shanghai

Sponsors (1)

Lead Sponsor	Collaborator
Shanghai Chest Hospital

Country where clinical trial is conducted

China, 

References & Publications (7)

Huang TC, Hsu CH, Lin CC, Tu YK. Systematic review and network meta-analysis: neoadjuvant chemoradiotherapy for locoregional esophageal cancer. Jpn J Clin Oncol. 2015 Nov;45(11):1023-8. doi: 10.1093/jjco/hyv119. Epub 2015 Aug 5. Review. — View Citation

Ikebe M, Morita M, Yamamoto M, Toh Y. Neoadjuvant therapy for advanced esophageal cancer: the impact on surgical management. Gen Thorac Cardiovasc Surg. 2016 Jul;64(7):386-94. doi: 10.1007/s11748-016-0655-y. Epub 2016 May 10. Review. — View Citation

Kumagai K, Rouvelas I, Tsai JA, Mariosa D, Klevebro F, Lindblad M, Ye W, Lundell L, Nilsson M. Meta-analysis of postoperative morbidity and perioperative mortality in patients receiving neoadjuvant chemotherapy or chemoradiotherapy for resectable oesophageal and gastro-oesophageal junctional cancers. Br J Surg. 2014 Mar;101(4):321-38. doi: 10.1002/bjs.9418. Epub 2014 Feb 3. Review. — View Citation

Martínek J, Akiyama JI, Vacková Z, Furnari M, Savarino E, Weijs TJ, Valitova E, van der Horst S, Ruurda JP, Goense L, Triadafilopoulos G. Current treatment options for esophageal diseases. Ann N Y Acad Sci. 2016 Jul 8. doi: 10.1111/nyas.13146. [Epub ahead of print] — View Citation

Purwar P, Bambarkar S, Jiwnani S, Karimundackal G, Laskar SG, Pramesh CS. Multimodality management of esophageal cancer. Indian J Surg. 2014 Dec;76(6):494-503. doi: 10.1007/s12262-014-1163-x. Epub 2014 Sep 11. — View Citation

Shapiro J, van Lanschot JJ, Hulshof MC, van Hagen P, van Berge Henegouwen MI, Wijnhoven BP, van Laarhoven HW, Nieuwenhuijzen GA, Hospers GA, Bonenkamp JJ, Cuesta MA, Blaisse RJ, Busch OR, Ten Kate FJ, Creemers GJ, Punt CJ, Plukker JT, Verheul HM, Bilgen EJ, van Dekken H, van der Sangen MJ, Rozema T, Biermann K, Beukema JC, Piet AH, van Rij CM, Reinders JG, Tilanus HW, Steyerberg EW, van der Gaast A; CROSS study group. Neoadjuvant chemoradiotherapy plus surgery versus surgery alone for oesophageal or junctional cancer (CROSS): long-term results of a randomised controlled trial. Lancet Oncol. 2015 Sep;16(9):1090-8. doi: 10.1016/S1470-2045(15)00040-6. Epub 2015 Aug 5. — View Citation

van Hagen P, Hulshof MC, van Lanschot JJ, Steyerberg EW, van Berge Henegouwen MI, Wijnhoven BP, Richel DJ, Nieuwenhuijzen GA, Hospers GA, Bonenkamp JJ, Cuesta MA, Blaisse RJ, Busch OR, ten Kate FJ, Creemers GJ, Punt CJ, Plukker JT, Verheul HM, Spillenaar Bilgen EJ, van Dekken H, van der Sangen MJ, Rozema T, Biermann K, Beukema JC, Piet AH, van Rij CM, Reinders JG, Tilanus HW, van der Gaast A; CROSS Group. Preoperative chemoradiotherapy for esophageal or junctional cancer. N Engl J Med. 2012 May 31;366(22):2074-84. doi: 10.1056/NEJMoa1112088. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of patients completing adjuvant chemoradiotherapy and surgery		4-8weeks after surgery	Yes
Secondary	Percentage of R0 resection		4-8weeks after surgery	Yes
Secondary	Percentage of pathological complete response		4-8weeks after surgery	Yes