Preoperative Chemoradiotherapy and Toripalimab in Locally Recurrent Rectal Cancer

NCT06751394 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: 2024ZSLYEC-684
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 1

Brief Summary

The study is a prospective, single-center, single-arm, phase II clinical trial. Patients with pelvic recurrent rectal cancer aged from 18 to 75 years, Eastern Cooperative Oncology Group performance status of 0-1, will receive 45-50Gy/25Fx irradiation or 30Gy/15Fx reirradiation (history of pelvic radiation). PD-1 inhibitor (Toripalimab) was used throughout the course of induction chemotherapy (before radiation), concurrent chemoradiation and consolidation chemotherapy (after radiation); radical resection was followed by well-experienced surgeons . The primary endpoint was pathological complete response (pCR) rate. Secondary endpoints were R0 resection rate, 3-year progression-free survival, overall survival, pathological tumor regression grade, operation characteristics and incidence of major surgical complications.

Conditions

Recurrent Rectal Cancer

Keywords

locally recurrent rectal cancer; PD-1 inhibitor; preoperative chemoradiotherapy

Outcome Measures

Primary Outcomes (1)

• Pathological complete response rate

  Defined as pathological evaluation of resected tumor tissue and regional lymph nodes, with no residual tumor cells, complete disappearance of all tumor lesions, and no appearance of new lesions.

  up to 1 year

Secondary Outcomes (6)

• R0 resection rate

  up to 1 year

• 3-year Progression-Free Survival

  up to 3 years

• Overall Survival

  up to 3 years

• Pathological tumor regression grading

  up to 1 year

• Operation complications

  up to 1 year

Study Arms (1)

Group A

EXPERIMENTAL

The patients will receive 2 cycles of XELOX or XELIRI and PD-1 antibody, followed by long course radiotherapy (45-50Gy/25f or 30Gy/25f), concurrent with Capecitabine and 1-2 cycles of PD-1 antibody, then receive 2-3 cycles of XELOX or XELIRI and PD-1 antibody. Curative surgery is scheduled after neoadjuvant treatment.

Drug: PD-1 antibody (Toripalimab); Drug: Capecitabine; Drug: Oxaliplatin; Drug: Irinotecan; Radiation: Radiation; Procedure: surgery

Interventions

PD-1 antibody (Toripalimab) DRUG

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

Group A

Capecitabine DRUG

Capecitabine:1000mg/m² d1-14 q3w; Capecitabine:825mg/m² on the day of radiotherapy

Group A

Oxaliplatin DRUG

130 mg/m² q3w

Group A

Irinotecan DRUG

200 mg/m² q3w

Group A

Radiation RADIATION

45-50Gy/25Fx or 30Gy/15Fx

Group A

surgery PROCEDURE

The type of surgery will depend on the site of recurrence and the involvement of adjacent structures, which will be determined by the surgeons.

Group A

Eligibility Criteria

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

You may qualify if:

• Patient is 18-75 years old at the time of signing the informed consent form.
• ECOG performance status 0-1.
• Pathological confirmed or MRI/ enhanced CT confirmed pelvic recurrence.
• No distant metastasis lesions outside the pelvic.
• No prior radiotherapy within 6 months.
• Participants with pelvic recurrence who have not previously been treated with first-line chemotherapy.
• Life expectancy at least 24 weeks.
• Adequate organ function (bone marrow, liver, kidney and clotting function) within 7 days before the first administration without using blood products or hematopoietic stimulating factors.
• Non pregnancy or lactation.
• Fully informed and willing to provide written informed consent for the trial.

You may not qualify if:

• Neutrophil \< 1.5×10\^9/L, PLT \< 75×10\^9/L.
• TBIL \> 1.5 ULN.
• AST or ALT \> 2.5 ULN, or ALT and / or AST \> 5 ULN in patients with liver metastasis.
• Cr \> 1.5 ULN.
• Serious electrolyte abnormalities.
• Active coronary artery disease, severe/unstable angina, or newly diagnosed angina or myocardial infarction within 12 months.
• Arterial thrombosis or deep vein thrombosis within 6 months, such as cerebrovascular accidents (including transient ischemic attacks), pulmonary embolism, deep vein thrombosis.
• Congestive cardiac failure ≥ NYHA grade 2.
• Human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS), untreated active hepatitis (hepatitis B defined as HBV-DNA ≥ 500 IU/ml; hepatitis C defined as HCV-RNA higher than lower limit of detection) or hepatitis B and hepatitis C virus co-infection.
• Active inflammatory bowel disease or other colorectal diseases that lead to chronic diarrhea.
• Suspected autoimmune disease.
• Interstitial lung disease, non-infectious pneumonia or uncontrollable systemic diseases (such as diabetes, hypertension, pulmonary fibrosis and acute pneumonia).
• Suspected allergic to any drugs used in the trial.
• History of any immune checkpoint inhibitor therapy.
• Clinically detectable second primary malignancy, or history of other malignancies within 5 years.

Sponsors & Collaborators

• Sixth Affiliated Hospital, Sun Yat-sen University: lead

Study Sites (1)

Sixth Affiliated Hospital, Sun Yat-sen University

Guangzhou, Guangdong, 510655, China

Location

MeSH Terms

Conditions

Rectal Neoplasms

Interventions

toripalimab; Capecitabine; Oxaliplatin; Irinotecan; Radiation; Surgical Procedures, Operative

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

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

Central Study Contacts

Xiaojian Wu

CONTACT

86-020-38455325; wuxjian@mail.sysu.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: hospital director

Study Record Dates

• First Submitted: December 19, 2024
• First Posted: December 27, 2024
• Study Start: January 1, 2025
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): December 31, 2028
• Last Updated: December 27, 2024

Record last verified: 2024-12

Locations

CN (1)