Back to resultsToripalimab Plus Neoadjuvant Chemotherapy Combined With Chemoradiotherapy for Locally Advanced Unresectable Esophageal Squamous Cell Carcinoma
Primary Purpose
Esophageal Squamous Cell Carcinoma
Status
Recruiting
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
Toripalimab
Paclitaxel-albumin
Nedaplatin
SMART
Capecitabine
Sponsored by
About this trial
This is an interventional treatment trial for Esophageal Squamous Cell Carcinoma focused on measuring Toripalimab, Neoadjuvant, Concurrent Chemoradiotherapy, Esophageal Squamous Cell Carcinoma
Eligibility Criteria
Inclusion Criteria:
- histologically confirmed esophageal squamous cell carcinoma
- patients have measurable or evaluable lesions based on the Response Evaluation Criteria in Solid Tumors (RECIST) criteria
- unresectable T2-4 N0-3 M0 confirmed by CT or MRI
- ECOG performance status 0-1
- no previous chest radiotherapy, immunotherapy or biotherapy.
- hemoglobin≥10 mg/dL, platelet≥100000/μL,absolute neutrophil count ≥1500/μL
- serum creatinine ≤1.25 times the upper normal limit(UNL), or creatinine clearance≥60 ml/min
- bilirubin ≤1.5 times UNL, AST（SGOT）≤2.5 times UNL ,ALT（SGPT）≤2.5 times UNL,alkaline phosphatase ≤5 times UNL
- FEV1 >0.8 L
- CB6 within normal limits
- patients and their family signed the informed consents
Exclusion Criteria:
- previous or recent another malignancy, except for nonmelanoma skin cancer or cervical cancer in situ
- contraindication for chemotherapy
- women in pregnancy, lactation period, or no pregnancy test 14 days before the first dose
- women who has the probability of pregnancy without contraception
- tendency of hemorrhage
- in other clinical trials within 30 days
- addicted in drugs or alcohol, AIDS patients
- uncontrollable seizure or psychotic patients without self-control ability
- severe allergy or idiosyncrasy
- not suitable for this study judged by researchers
Sites / Locations
- Sun yat-sen University Cancer CenterRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Toripalimab plus Paclitaxel/Nedaplatin followed by concurrent chemoradiotherapy
Arm Description
Patients in experimental group receive 2 cycles Toripalimab plus Paclitaxel/Nedaplatin, then followed by daily simultaneous modulated accelerated radiotherapy combined with Capecitabine.
Outcomes
Primary Outcome Measures
2-year progression-free survival rate
Secondary Outcome Measures
2-year overall survival rate
Clinical response rate
the percentage of patients who had partial remission or complete remission after therapy
the rate of grade 3 or 4 toxicities according to CTCAE4.0
the percentage of patients who develop grade 3 or 4 toxicities
2-year distant metastasis-free survival
2-year locoregional recurrence-free survival
Quality of life assessed by QLQ-C30
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04844385
Brief Title
Toripalimab Plus Neoadjuvant Chemotherapy Combined With Chemoradiotherapy for Locally Advanced Unresectable Esophageal Squamous Cell Carcinoma
Official Title
A Prospective Single-arm Phase Ⅱ Study of Toripalimab Plus Neoadjuvant Chemotherapy Combined With Chemoradiotherapy for Locally Advanced Unresectable Esophageal Squamous Cell Carcinoma
Study Type
Interventional
2. Study Status
Record Verification Date
October 2022
Overall Recruitment Status
Recruiting
Study Start Date
February 20, 2021 (Actual)
Primary Completion Date
January 2024 (Anticipated)
Study Completion Date
July 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Sun Yat-sen University
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
Brief Summary
This Phase II randomized study is to determine the efficacy and toxicity of toripalimab plus neoadjuvant chemotherapy combined with chemoradiotherapy for locally advanced unresectable esophageal squamous cell carcinoma.
Detailed Description
This Phase II randomized study is to determine the efficacy and toxicity of toripalimab plus neoadjuvant chemotherapy combined with chemoradiotherapy for locally advanced unresectable esophageal squamous cell carcinoma.
All patients were planned to receive 2 cycle of toripalimab plus paclitaxel/nedaplatin as neoadjuvant therapy. Then they all receive radical dose of chest radiation and concurrent chemotherapy of capecitabine (PO 1000 mg/m2, bid, d1-d14, q3w).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Esophageal Squamous Cell Carcinoma
Keywords
Toripalimab, Neoadjuvant, Concurrent Chemoradiotherapy, Esophageal Squamous Cell Carcinoma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
83 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Toripalimab plus Paclitaxel/Nedaplatin followed by concurrent chemoradiotherapy
Arm Type
Experimental
Arm Description
Patients in experimental group receive 2 cycles Toripalimab plus Paclitaxel/Nedaplatin, then followed by daily simultaneous modulated accelerated radiotherapy combined with Capecitabine.
Intervention Type
Drug
Intervention Name(s)
Toripalimab
Intervention Description
Toripalimab 240 mg, d1, Q3w for two cycles
Intervention Type
Drug
Intervention Name(s)
Paclitaxel-albumin
Intervention Description
Paclitaxel-albumin 260 mg/m2, d1, Q3w for two cycles
Intervention Type
Drug
Intervention Name(s)
Nedaplatin
Intervention Description
Nedaplatin 75mg/m2, d1, Q3w for two cycles
Intervention Type
Radiation
Intervention Name(s)
SMART
Intervention Description
Once-daily simultaneous modulated accelerated radiotherapy (PTV-GTV: 60Gy/24f )
Intervention Type
Drug
Intervention Name(s)
Capecitabine
Intervention Description
Capecitabine 1000 mg/m2, bid, d1-14, q3w during radiotherapy
Primary Outcome Measure Information:
Title
2-year progression-free survival rate
Time Frame
2-year
Secondary Outcome Measure Information:
Title
2-year overall survival rate
Time Frame
2-year
Title
Clinical response rate
Description
the percentage of patients who had partial remission or complete remission after therapy
Time Frame
2 months after radiotherapy
Title
the rate of grade 3 or 4 toxicities according to CTCAE4.0
Description
the percentage of patients who develop grade 3 or 4 toxicities
Time Frame
1 year after therapy
Title
2-year distant metastasis-free survival
Time Frame
2-year
Title
2-year locoregional recurrence-free survival
Time Frame
2-year
Title
Quality of life assessed by QLQ-C30
Time Frame
2-year
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
histologically confirmed esophageal squamous cell carcinoma
patients have measurable or evaluable lesions based on the Response Evaluation Criteria in Solid Tumors (RECIST) criteria
unresectable T2-4 N0-3 M0 confirmed by CT or MRI
ECOG performance status 0-1
no previous chest radiotherapy, immunotherapy or biotherapy.
hemoglobin≥10 mg/dL, platelet≥100000/μL,absolute neutrophil count ≥1500/μL
serum creatinine ≤1.25 times the upper normal limit(UNL), or creatinine clearance≥60 ml/min
bilirubin ≤1.5 times UNL, AST（SGOT）≤2.5 times UNL ,ALT（SGPT）≤2.5 times UNL,alkaline phosphatase ≤5 times UNL
FEV1 >0.8 L
CB6 within normal limits
patients and their family signed the informed consents
Exclusion Criteria:
previous or recent another malignancy, except for nonmelanoma skin cancer or cervical cancer in situ
contraindication for chemotherapy
women in pregnancy, lactation period, or no pregnancy test 14 days before the first dose
women who has the probability of pregnancy without contraception
tendency of hemorrhage
in other clinical trials within 30 days
addicted in drugs or alcohol, AIDS patients
uncontrollable seizure or psychotic patients without self-control ability
severe allergy or idiosyncrasy
not suitable for this study judged by researchers
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Bo Qiu, Professor
Phone
+86-020-87343031
Email
qiubo@sysucc.org.cn
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Hui Liu, Professor
Organizational Affiliation
Sun yat-sen universtiy cancer center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Sun yat-sen University Cancer Center
City
Guangzhou
State/Province
Guangdong
ZIP/Postal Code
510000
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Bo Qiu, Professor
Phone
020-87343031
Email
qiubo@sysucc.org.cn
12. IPD Sharing Statement
Citations:
PubMed Identifier
30207593
Citation
Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018 Nov;68(6):394-424. doi: 10.3322/caac.21492. Epub 2018 Sep 12. Erratum In: CA Cancer J Clin. 2020 Jul;70(4):313.
Results Reference
background
PubMed Identifier
10235156
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.
Results Reference
background
PubMed Identifier
11870157
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.
Results Reference
background
PubMed Identifier
30920880
Citation
Chen Y, Ye J, Zhu Z, Zhao W, Zhou J, Wu C, Tang H, Fan M, Li L, Lin Q, Xia Y, Li Y, Li J, Jia H, Lu S, Zhang Z, Zhao K. Comparing Paclitaxel Plus Fluorouracil Versus Cisplatin Plus Fluorouracil in Chemoradiotherapy for Locally Advanced Esophageal Squamous Cell Cancer: A Randomized, Multicenter, Phase III Clinical Trial. J Clin Oncol. 2019 Jul 10;37(20):1695-1703. doi: 10.1200/JCO.18.02122. Epub 2019 Mar 28.
Results Reference
background
PubMed Identifier
10699886
Citation
Gaspar LE, Winter K, Kocha WI, Coia LR, Herskovic A, Graham M. A phase I/II study of external beam radiation, brachytherapy, and concurrent chemotherapy for patients with localized carcinoma of the esophagus (Radiation Therapy Oncology Group Study 9207): final report. Cancer. 2000 Mar 1;88(5):988-95.
Results Reference
background
PubMed Identifier
33026938
Citation
Kojima T, Shah MA, Muro K, Francois E, Adenis A, Hsu CH, Doi T, Moriwaki T, Kim SB, Lee SH, Bennouna J, Kato K, Shen L, Enzinger P, Qin SK, Ferreira P, Chen J, Girotto G, de la Fouchardiere C, Senellart H, Al-Rajabi R, Lordick F, Wang R, Suryawanshi S, Bhagia P, Kang SP, Metges JP; KEYNOTE-181 Investigators. Randomized Phase III KEYNOTE-181 Study of Pembrolizumab Versus Chemotherapy in Advanced Esophageal Cancer. J Clin Oncol. 2020 Dec 10;38(35):4138-4148. doi: 10.1200/JCO.20.01888. Epub 2020 Oct 7.
Results Reference
background
PubMed Identifier
30735435
Citation
Kato K, Shah MA, Enzinger P, Bennouna J, Shen L, Adenis A, Sun JM, Cho BC, Ozguroglu M, Kojima T, Kostorov V, Hierro C, Zhu Y, McLean LA, Shah S, Doi T. KEYNOTE-590: Phase III study of first-line chemotherapy with or without pembrolizumab for advanced esophageal cancer. Future Oncol. 2019 Apr;15(10):1057-1066. doi: 10.2217/fon-2018-0609. Epub 2019 Feb 8.
Results Reference
background
PubMed Identifier
23426016
Citation
Fan TY, Xing J, Lu J, Liu TH, Xu M, Zhang YJ, Shao Q, Li JB, Yu JM. Phase I/II study of induction chemotherapy plus concurrent chemotherapy and SMART-IMRT-based radiotherapy in locoregionally-advanced nasopharyngeal cancer. Oncol Lett. 2013 Mar;5(3):889-895. doi: 10.3892/ol.2013.1137. Epub 2013 Jan 15.
Results Reference
background
PubMed Identifier
17764088
Citation
Koom WS, Kim TH, Shin KH, Pyo HR, Kim JY, Kim DY, Yoon M, Park SY, Lee DH, Ryu JS, Jung YS, Lee SH, Cho KH. SMART (simultaneous modulated accelerated radiotherapy) for locally advanced nasopharyngeal carcinomas. Head Neck. 2008 Feb;30(2):159-69. doi: 10.1002/hed.20667.
Results Reference
background
PubMed Identifier
10477002
Citation
Butler EB, Teh BS, Grant WH 3rd, Uhl BM, Kuppersmith RB, Chiu JK, Donovan DT, Woo SY. Smart (simultaneous modulated accelerated radiation therapy) boost: a new accelerated fractionation schedule for the treatment of head and neck cancer with intensity modulated radiotherapy. Int J Radiat Oncol Biol Phys. 1999 Aug 1;45(1):21-32. doi: 10.1016/s0360-3016(99)00101-7.
Results Reference
background
PubMed Identifier
21123005
Citation
Welsh J, Palmer MB, Ajani JA, Liao Z, Swisher SG, Hofstetter WL, Allen PK, Settle SH, Gomez D, Likhacheva A, Cox JD, Komaki R. Esophageal cancer dose escalation using a simultaneous integrated boost technique. Int J Radiat Oncol Biol Phys. 2012 Jan 1;82(1):468-74. doi: 10.1016/j.ijrobp.2010.10.023. Epub 2010 Dec 1.
Results Reference
background
PubMed Identifier
21214285
Citation
Song YP, Ma JB, Hu LK, Zhou W, Chen EC, Zhang W. Phase I/II study of hypofractioned radiation with three-dimensional conformal radiotherapy for clinical T3-4N0-1M0 stage esophageal carcinoma. Technol Cancer Res Treat. 2011 Feb;10(1):25-30. doi: 10.7785/tcrt.2012.500176.
Results Reference
background
PubMed Identifier
23098423
Citation
Ma JB, Wei L, Chen EC, Qin G, Song YP, Chen XM, Hao CG. Moderately hypofractionated conformal radiation treatment of thoracic esophageal carcinoma. Asian Pac J Cancer Prev. 2012;13(8):4163-7. doi: 10.7314/apjcp.2012.13.8.4163.
Results Reference
background
Learn more about this trial
Toripalimab Plus Neoadjuvant Chemotherapy Combined With Chemoradiotherapy for Locally Advanced Unresectable Esophageal Squamous Cell Carcinoma
We'll reach out to this number within 24 hrs