Clinical trial NCT04518280: Short-course Radiotherapy Based TNT Combined With PD-1 Inhibitor for Locally Advanced Rectal Cancer
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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Locally Advanced Rectal Cancer
Lead sponsor: Fudan University
Sponsor class: OTHER
First posted: 2020-08-19
Enrollment: 130
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

1. Pathological confrmed adenocarcinoma
2. Clinical stage T3-4 and/or N+
3. The distance from anal verge ≤12 cm
4. Without distance metastases
5. Age 18-70 years old, female and male
6. KPS \> =70
7. 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
8. With good compliance and signed the consent form

Exclusion Criteria:

1. Pregnancy or breast-feeding women
2. Known history of other malignancies within 5 years
3. Known history of previous anti-tumor treatment, including radiotherapy, chemotherapy, immune checkpoint inhibitors, T cell-related therapy, etc
4. Known history of severe neurological or mental illness (such as schizophrenia, dementia or epilepsy)
5. Current severe cardiac disease (cardiac dysfunction and arrhythmia), renal dysfunction and liver dysfunction
6. Acute cardiac infarction or cerebral ischemic stroke occurred within 6 months before recruitment
7. Uncontrolled infection which needs systemic therapy
8. Active autoimmune disease or immunodefciencies, known history of organ transplantation or systematic use of immunosuppressive agents
9. Known history of human immunodefciency virus (HIV) infection (i.e., HIV 1 to 2 antibody positive), active syphilis infection, active pulmonary tuberculosis infection
10. 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)
11. Allergic to any component of the therapy

Primary outcomes:
measure: Complete response (CR) rate
timeFrame: 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 outcomes:
measure: Grade 3-4 adverse effects rate
timeFrame: From date of randomization until the date of death from any cause, assessed up to 5 years
measure: 3 year disease free survival rate
timeFrame: 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.
measure: 3 year local recurrence free survival rate
timeFrame: From date of randomization until the date of first documented pelvic failure, assessed up to 36 months.
measure: 3 year overall survival rate
timeFrame: From date of randomization until the date of death from any cause, assessed up to 36 months.
measure: Rate of Surgical complications
timeFrame: 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.
measure: Scores of Quality of Life
timeFrame: From date of randomization until the date of death from any cause, assessed up to 10 years
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Shanghai Changhai Hospital
state: Shanghai
city: Shanghai
country: China
facility: Zhen Zhang
state: Shanghai
city: Shanghai
country: China
facility: Shanghai East Hospital
Study officials:
affiliation: Fudan University
name: Zhen Zhang, M.D, PH.D
role: PRINCIPAL_INVESTIGATOR
References:
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.