Short-course Radiotherapy Based TNT Combined With PD-1 Inhibitor for Locally Advanced Rectal Cancer (TORCH)
Primary Purpose
Locally Advanced Rectal Cancer
Status
Recruiting
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
PD-1 antibody
Capecitabine
Oxaliplatin
Short-course radiotherapy
Sponsored by
About this trial
This is an interventional treatment trial for Locally Advanced Rectal Cancer
Eligibility Criteria
Inclusion Criteria:
- pathological confirmed adenocarcinoma
- clinical stage T3-4 and/or N+
- the distance from anal verge less than 12 cm
- without distance metastases
- age 18-70 years old, female and male
- KPS >=70
- without previous anti-cancer therapy or immunotherapy
- with good compliance
- signed the inform consent
Exclusion Criteria:
- pregnancy or breast-feeding women
- history of other malignancies within 5 years
- serious medical illness, such as severe mental disorders, cardiac disease, uncontrolled infection, etc.
- immunodeficiency disease or long-term using of immunosuppressive agents
- baseline blood and biochemical indicators do not meet the following criteria: neutrophils≥1.5×10^9/L, Hb≥90g/L, PLT≥100×10^9/L, ALT/AST ≤2.5 ULN, Cr≤ 1 ULN
- DPD deficiency
- allergic to any component of the therapy
Sites / Locations
- Shanghai Changhai HospitalRecruiting
- Shanghai Changzheng Hospital
- Zhen ZhangRecruiting
- Shanghai East HospitalRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Group A
Group B
Arm Description
The patients will receive short-course radiotherapy (25Gy/5Fx), followed by 6 cycles of CAPOX and PD-1 antibody. TME surgery is scheduled after TNT while a W&W option can be applied to patients achieving cCR.
The patients will firstly receive 2 cycles of CAPOX and PD-1 antibody, then receive short-course radiotherapy (25Gy/5Fx), followed by 4 cycles of CAPOX and PD-1 antibody. TME surgery is scheduled after TNT while a W&W option can be applied to patients achieving cCR.
Outcomes
Primary Outcome Measures
Complete response (CR) rate
Rate of complete response (CR), including the rate of pathologic complete response (pCR) after surgery and the rate of cCR with W&W strategy.
Secondary Outcome Measures
Grade 3-4 adverse effects rate
Rate of chemotherapy, radiotherapy and immunotherapy related adverse events
3 year disease free survival rate
Rate of 3 year disease free survival
3 year local recurrence free survival rate
Rate of 3 year local recurrence free survival
3 year overall survival rate
Rate of 3 year overall survival
Rate of Surgical complications
Rate of surgical complications, such as intraoperative hemorrhage, anastomotic leakage, intestinal obstruction, etc.
Scores of Quality of Life
Quality of life will be evaluated using EORTC QLQ-C30, EORTC QLQ-CR29, LARS score and Wexner score.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04518280
Brief Title
Short-course Radiotherapy Based TNT Combined With PD-1 Inhibitor for Locally Advanced Rectal Cancer
Acronym
TORCH
Official Title
A Prospective Phase II Trial of Short-course Radiotherapy Based Total Neoadjuvant Therapy Combined With PD-1 Inhibitor for Locally Advanced Rectal Cancer (TORCH)
Study Type
Interventional
2. Study Status
Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
May 1, 2021 (Actual)
Primary Completion Date
October 1, 2023 (Anticipated)
Study Completion Date
December 31, 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Fudan 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
TORCH is a prospective, multicentre, randomized phase II trial. 130 LARC (T3-4/N+M0, distance from anal verge ≤12cm) patients will be treated with total neoadjuvant therapy (TNT) and assigned to Group A and Group B. Group A receives SCRT (25Gy/5Fx) followed by 6 cycles of Toripalimab combined with CAPOX (ToriCAPOX). Group B receives 2 cycles of ToriCAPOX followed by SCRT and 4 cycles of ToriCAPOX. TME surgery is scheduled after TNT while a watch and wait (W&W) option can be applied to patients achieving clinical complete response (cCR). The primary endpoint is complete response (CR, pathological complete response [pCR] plus cCR) rate. The secondary endpoints include the grade 3-4 acute adverse effects (AE) rate, 3-year DFS rate, etc.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Locally Advanced Rectal Cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
130 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Group A
Arm Type
Experimental
Arm Description
The patients will receive short-course radiotherapy (25Gy/5Fx), followed by 6 cycles of CAPOX and PD-1 antibody. TME surgery is scheduled after TNT while a W&W option can be applied to patients achieving cCR.
Arm Title
Group B
Arm Type
Experimental
Arm Description
The patients will firstly receive 2 cycles of CAPOX and PD-1 antibody, then receive short-course radiotherapy (25Gy/5Fx), followed by 4 cycles of CAPOX and PD-1 antibody. TME surgery is scheduled after TNT while a W&W option can be applied to patients achieving cCR.
Intervention Type
Drug
Intervention Name(s)
PD-1 antibody
Other Intervention Name(s)
Toripalimab
Intervention Description
PD-1 antibody (Toripalimab): 240mg d1 q3w
Intervention Type
Drug
Intervention Name(s)
Capecitabine
Other Intervention Name(s)
Xeloda
Intervention Description
Capecitabine: 1000mg/m2 bid d1-14 q3w
Intervention Type
Drug
Intervention Name(s)
Oxaliplatin
Intervention Description
Oxaliplatin: 130mg/m2 d1 q3w
Intervention Type
Radiation
Intervention Name(s)
Short-course radiotherapy
Intervention Description
Shor-course radiotherapy: 25Gy/5Fx
Primary Outcome Measure Information:
Title
Complete response (CR) rate
Description
Rate of complete response (CR), including the rate of pathologic complete response (pCR) after surgery and the rate of cCR with W&W strategy.
Time Frame
The status of cCR will be evaluated after the completion of neoadjuvant therapy. The pCR rate will be evaluated after surgery. The cCR patients who adopted W&W strategy will be included into the CR rate caluculation.
Secondary Outcome Measure Information:
Title
Grade 3-4 adverse effects rate
Description
Rate of chemotherapy, radiotherapy and immunotherapy related adverse events
Time Frame
From date of randomization until the date of death from any cause, assessed up to 5 years
Title
3 year disease free survival rate
Description
Rate of 3 year disease free survival
Time Frame
From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months.
Title
3 year local recurrence free survival rate
Description
Rate of 3 year local recurrence free survival
Time Frame
From date of randomization until the date of first documented pelvic failure, assessed up to 36 months.
Title
3 year overall survival rate
Description
Rate of 3 year overall survival
Time Frame
From date of randomization until the date of death from any cause, assessed up to 36 months.
Title
Rate of Surgical complications
Description
Rate of surgical complications, such as intraoperative hemorrhage, anastomotic leakage, intestinal obstruction, etc.
Time Frame
The surgery was scheduled 2-4 weeks after the end of neoadjuvant therapy. And the surgical complications were assessed up to 5 years from the surgery.
Title
Scores of Quality of Life
Description
Quality of life will be evaluated using EORTC QLQ-C30, EORTC QLQ-CR29, LARS score and Wexner score.
Time Frame
From date of randomization until the date of death from any cause, assessed up to 10 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Pathological confrmed adenocarcinoma
Clinical stage T3-4 and/or N+
The distance from anal verge ≤12 cm
Without distance metastases
Age 18-70 years old, female and male
KPS > =70
Baseline blood and biochemical indicators meet the following criteria: neutrophils≥1.5×10^9/L, Hb≥90 g/L, PLT≥100×10^9/L, ALT/AST≤2.5 ULN, Cr≤1 ULN
With good compliance and signed the consent form
Exclusion Criteria:
Pregnancy or breast-feeding women
Known history of other malignancies within 5 years
Known history of previous anti-tumor treatment, including radiotherapy, chemotherapy, immune checkpoint inhibitors, T cell-related therapy, etc
Known history of severe neurological or mental illness (such as schizophrenia, dementia or epilepsy)
Current severe cardiac disease (cardiac dysfunction and arrhythmia), renal dysfunction and liver dysfunction
Acute cardiac infarction or cerebral ischemic stroke occurred within 6 months before recruitment
Uncontrolled infection which needs systemic therapy
Active autoimmune disease or immunodefciencies, known history of organ transplantation or systematic use of immunosuppressive agents
Known history of human immunodefciency virus (HIV) infection (i.e., HIV 1 to 2 antibody positive), active syphilis infection, active pulmonary tuberculosis infection
Active Hepatitis B virus (HBV) or hepatitis C virus (HCV) infection at screening (i.e., HBsAg positive or HBV DNA positive, HCV RNA positive if anti-HCV antibody testing positive)
Allergic to any component of the therapy
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Zhen Zhang, M.D, PH.D
Phone
18801735029
Ext
18801735029
Email
zhen_zhang@fudan.edu.cn
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Zhen Zhang, M.D, PH.D
Organizational Affiliation
Fudan University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Shanghai Changhai Hospital
City
Shanghai
State/Province
Shanghai
ZIP/Postal Code
200032
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Huojun Zhang, M.D, PH.D
Email
mxjtg123@126.com
Facility Name
Shanghai Changzheng Hospital
City
Shanghai
State/Province
Shanghai
ZIP/Postal Code
200032
Country
China
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Zhiqian Hu, M.D, PH.D
Email
1374162606@qq.com
Facility Name
Zhen Zhang
City
Shanghai
State/Province
Shanghai
ZIP/Postal Code
200032
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Zhen Zhang, M.D, PH.D
Phone
18801735029
Ext
18801735029
Email
zhen_zhang@fudan.edu.cn
Facility Name
Shanghai East Hospital
City
Shanghai
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Zuolin Xiang
12. IPD Sharing Statement
Citations:
PubMed Identifier
35291966
Citation
Wang Y, Shen L, Wan J, Zhang H, Wu R, Wang J, Wang Y, Xu Y, Cai S, Zhang Z, Xia F. Short-course radiotherapy combined with CAPOX and Toripalimab for the total neoadjuvant therapy of locally advanced rectal cancer: a randomized, prospective, multicentre, double-arm, phase II trial (TORCH). BMC Cancer. 2022 Mar 15;22(1):274. doi: 10.1186/s12885-022-09348-z.
Results Reference
derived
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Short-course Radiotherapy Based TNT Combined With PD-1 Inhibitor for Locally Advanced Rectal Cancer
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