MR-guided Adaptive Radiotherapy Combined With PD-1 Antibody and CAPOX for Locally Advanced Rectal Cancer

NCT06840665 | Recruiting Phase 2

• 1 other identifier: FDRT-2024-293-3847
• Study Type: interventional
• Target: 46
• Locations: 1 country
• Sites: 1

Brief Summary

NeoPulsar is a prospective, randomized phase II trial. 46 LARC (T3-4/N+M0, distance from anal verge ≤12cm) patients will be treated with MR-guided adaptive radiotherapy (30Gy/6Fx) combined with 6 cycles of Toripalimab and CAPOX. TME surgery is scheduled after TNT. The primary endpoint is pathological complete response (pCR) rate. The secondary endpoints include the grade 3-4 acute adverse effects (AE) rate, anal function, surgical complication, 3-year LRFS rate, 3-year DFS rate, 3-year OS rate, etc.

Conditions

Locally Advanced Rectal Cancer

Outcome Measures

Primary Outcomes (1)

• Pathological complete response (pCR) rate

  Rate of pathologic complete response (pCR) after surgery

  1 month after the surgery

Secondary Outcomes (6)

• Grade 3-4 adverse effects rate

  From the date of randomization until 3 months after the completion neoadjuvant therapy

• Anal function

  From the date of randomization until 36 months after the surgery

• Surgical complication

  The surgical complications were assessed within 3 months after the surgery

• 3-year local recurrence free survival (LRFS) rate

  From the date of randomization until the date of first documented pelvic failure, assessed up to 36 months

• 3-year disease free survival (DFS) rate

  From the 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

Study Arms (2)

Group A

EXPERIMENTAL

The patients will receive conventional pelvic radiotherapy (30Gy/6Fx), combined with 6 cycles of CAPOX and PD-1 antibody. TME surgery is scheduled after TNT.

Drug: PD-1 antibody; Drug: Oxaliplatin; Drug: Capecitabine

Group B

EXPERIMENTAL

The patients will receive lymph node-sparing radiotherapy (30Gy/6Fx), combined with 6 cycles of CAPOX and PD-1 antibody. TME surgery is scheduled after TNT.

Drug: PD-1 antibody; Drug: Oxaliplatin; Drug: Capecitabine

Interventions

PD-1 antibody DRUG

PD-1 antibody (Toripalimab): 240mg d1 q3w

Also known as: Toripalimab

Group A; Group B

Oxaliplatin DRUG

Oxaliplatin: 130mg/m2 d1 q3w

Group A; Group B

Capecitabine DRUG

Capecitabine: 1000mg/m2 bid d1-14 q3w

Group A; Group B

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18-70 years old, male or female
• Pathologically confirmed rectal adenocarcinoma
• The distance from anal verge ≤ 10 cm
• Clinical stage T3-4 and/or N+
• No evidence of distance metastases
• MSI/MMR status: MSS/pMMR
• Karnofsky score \>=70
• Adequate organ function and have no contraindications to surgery, radiochemotherapy, or immunotherapy
• No chemotherapy or any other anti-tumor therapy prior to enrollment
• No immunotherapy prior to enrollment
• With good compliance during the study
• Signed written informed consent

You may not qualify if:

• Known history of other malignancies within 5 years， except cured skin cancer and cervical cancer in situ
• Pregnancy or breast-feeding women
• Individuals with a history of uncontrolled epilepsy, central nervous system disease, or psychiatric disorders that, in the judgment of the investigator, are of such clinical severity that they may prevent the signing of an informed consent form or affect the patient's adherence to oral medications
• Individuals with clinically serious (i.e., active) heart disease, such as symptomatic coronary artery disease, New York Heart Association (NYHA) class II or worse congestive heart failure or severe arrhythmia requiring pharmacologic intervention, or history of myocardial infarction within the last 12 months
• Individuals with a history of organ transplantation requiring immunosuppressive therapy and long-term hormone therapy
• Individuals with autoimmune diseases
• Individuals with severe uncontrolled recurrent infections，or other severe uncontrolled concomitant diseases
• Baseline hematology and biochemistry not meeting the following criteria: Hb≥90g/L; NEU ≥1.5×109/L; PLT ≥100×109/L; ALT, AST ≤2.5 times the upper limit of normal; ALP ≤2.5 times the upper limit of normal; TB \<1.5 times the upper limit of normal; Cr \<1 time the upper limit of normal; Alb ≥30g/L
• Individuals with dihydropyrimidine dehydrogenase (DPD) deficiency
• Individuals allergic to any drug component of the study

Sponsors & Collaborators

• Fudan University: lead

Study Sites (1)

Fudan University Shanghai Cancer Center

Shanghai, Shanghai Municipality, 200030, China

RECRUITING

MeSH Terms

Interventions

spartalizumab; toripalimab; Oxaliplatin; Capecitabine

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Central Study Contacts

Zhen Zhang, MD

CONTACT

+86 18017312217; zhen_zhang@fudan.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Study Principal Investigator

Study Record Dates

• First Submitted: February 15, 2025
• First Posted: February 21, 2025
• Study Start: August 13, 2024
• Primary Completion (Estimated): August 12, 2026
• Study Completion (Estimated): February 12, 2027
• Last Updated: February 21, 2025

Record last verified: 2025-02

Locations

CN (1)