Clinical trial NCT02429622: Simultaneous Integrated Boost Radiotherapy and Concurrent Chemotherapy for Locally Advanced Esophageal Carcinoma
Official title: A Phase Ⅰ/Ⅱ Study of Simultaneous Integrated Boost Radiotherapy and Concurrent Chemotherapy in Patients With Locally Advanced Esophageal Carcinoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Esophageal Neoplasms
Lead sponsor: ChineseAMS
Sponsor class: UNKNOWN
First posted: 2015-04-29
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Maximum age (years): 72
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This phase Ⅰ/Ⅱ trial is designed to explore a higher radiation dose by using IMRT simultaneous integrated boost technique with or without concurrent chemotherapy for locally advanced esophageal carcinoma.

Detailed description: Despite the application of IMRT and the studies of concurrent chemoradiation in esophageal carcinoma, which improves 5-year survival rate from 10% to 20%-40% and decrease recurrence rate from 80% to 50%-60%, local recurrence remains to be the most common failure pattern. Therefore, enhancing local control is the key to obtain a better survival.

A phase Ⅱ study of radical radiotherapy with IMRT simultaneous integrated boost technique and concurrent chemotherapy for esophageal carcinoma use the same radiation dose as the high dose arm in RTOG 94-05, which reveals an significantly improved median survival time of 23 months and 3-year overall survival rate of 44.4%. This study implies the simultaneous integrated boost technique may be effective to some extent. But the question is how to identify patients who may gain potential benefits, and whether this therapeutic model can be copied in the specific situation in China? Few adverse effects such as perforation, hemorrhage and stenosis was reported, mainly owing to the lack of cases. For widely application of this new technique in the clinic, more studies need to be conducted in the future to obtain sufficient evidence.

The current IMRT can simultaneously achieve prophylactic dose (DT 50Gy) and radical dose (DT 60-64Gy) in respective target volume by using inverse intensity-modulated planning system. However, it is still controversial on whether esophageal carcinoma can receive prescription dose more than 2.0Gy each time. That is to say, it is challengeable to find an optimal fraction dose and total dose between tumor and adverse effects. For this reason, the dose escalation trial is to be conducted to explore the clinical value and optimal dose to esophageal carcinoma with different radiosensitivity, and also provide data support for phase Ⅲ clinical trials.

Eligibility criteria: Inclusion Criteria:

* Diagnosis of clinical stage T2-4N0-1M1a untreated squamous esophageal carcinoma
* KPS≥70
* Adequate organ function
* No known history of drug allergy

Exclusion Criteria:

* Known drug allergy
* Insufficient hepatorenal function
* Severe cardiovascular diseases, diabetes with uncontrolled blood sugar, mental disorders, uncontrolled severe infection, active ulceration which need intervention.

Primary outcomes:
measure: Disease-free survival (DFS)
timeFrame: up to 3 years
Secondary outcomes:
measure: Overall survival (OS)
timeFrame: up to 5 years
Other outcomes:
measure: Adverse events
timeFrame: up to 5 years
Locations:
city: Beijing
country: China
facility: Zefen Xiao
state: Beijing
Study officials:
affiliation: The Department of Radiation Oncology ,Cancer Institute & Hospital，Chinese Academy of Medical Science
name: Zefen Xiao, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Cooper JS, Guo MD, Herskovic A, Macdonald JS, Martenson JA Jr, Al-Sarraf M, Byhardt R, Russell AH, Beitler JJ, Spencer S, Asbell SO, Graham MV, Leichman LL. Chemoradiotherapy of locally advanced esophageal cancer: long-term follow-up of a prospective randomized trial (RTOG 85-01). Radiation Therapy Oncology Group. JAMA. 1999 May 5;281(17):1623-7. doi: 10.1001/jama.281.17.1623.
citation: Welsh J, Settle SH, Amini A, Xiao L, Suzuki A, Hayashi Y, Hofstetter W, Komaki R, Liao Z, Ajani JA. Failure patterns in patients with esophageal cancer treated with definitive chemoradiation. Cancer. 2012 May 15;118(10):2632-40. doi: 10.1002/cncr.26586. Epub 2011 Oct 5.
citation: Minsky BD, Pajak TF, Ginsberg RJ, Pisansky TM, Martenson J, Komaki R, Okawara G, Rosenthal SA, Kelsen DP. INT 0123 (Radiation Therapy Oncology Group 94-05) phase III trial of combined-modality therapy for esophageal cancer: high-dose versus standard-dose radiation therapy. J Clin Oncol. 2002 Mar 1;20(5):1167-74. doi: 10.1200/JCO.2002.20.5.1167.
citation: Yu WW, Zhu ZF, Fu XL, Zhao KL, Mao JF, Wu KL, Yang HJ, Fan M, Zhao S, Welsh J. Simultaneous integrated boost intensity-modulated radiotherapy in esophageal carcinoma: early results of a phase II study. Strahlenther Onkol. 2014 Oct;190(11):979-86. doi: 10.1007/s00066-014-0636-y. Epub 2014 Mar 8.
citation: Li C, Ni W, Wang X, Zhou Z, Deng W, Chang X, Chen D, Feng Q, Liang J, Wang X, Deng L, Wang W, Bi N, Zhang T, Xiao Z. A phase I/II radiation dose escalation trial using simultaneous integrated boost technique with elective nodal irradiation and concurrent chemotherapy for unresectable esophageal Cancer. Radiat Oncol. 2019 Mar 15;14(1):48. doi: 10.1186/s13014-019-1249-5.