Preoperative Chemoradiotherapy and Toripalimab in Locally Recurrent Rectal Cancer (TRACER)

Preoperative Treatment with Radiotherapy and Anti-PD1 for Resectable Recurrent Rectal Cancer (TRACER)

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Recurrent Rectal Cancer
• Intervention / Treatment: Drug: PD-1 antibody (Toripalimab); Drug: Capecitabine; Drug: Oxaliplatin; Drug: Irinotecan; Radiation: Radiation; Procedure: surgery

• Study Type: Interventional
• Enrollment (Estimated): 44
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Xiaojian Wu; Phone Number: 86-020-38455325; Email: wuxjian@mail.sysu.edu.cn

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510655
      • Sixth Affiliated Hospital, Sun Yat-sen University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Patient is 18-75 years old at the time of signing the informed consent form.
2. ECOG performance status 0-1.
3. Pathological confirmed or MRI/ enhanced CT confirmed pelvic recurrence.
4. No distant metastasis lesions outside the pelvic.
5. No prior radiotherapy within 6 months.
6. Participants with pelvic recurrence who have not previously been treated with first-line chemotherapy.
7. Life expectancy at least 24 weeks.
8. 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.
9. Non pregnancy or lactation.
10. Fully informed and willing to provide written informed consent for the trial.

Exclusion Criteria:

1. Neutrophil < 1.5×10^9/L, PLT < 75×10^9/L.
2. TBIL > 1.5 ULN.
3. AST or ALT > 2.5 ULN, or ALT and / or AST > 5 ULN in patients with liver metastasis.
4. Cr > 1.5 ULN.
5. Serious electrolyte abnormalities.
6. Active coronary artery disease, severe/unstable angina, or newly diagnosed angina or myocardial infarction within 12 months.
7. Arterial thrombosis or deep vein thrombosis within 6 months, such as cerebrovascular accidents (including transient ischemic attacks), pulmonary embolism, deep vein thrombosis.
8. Congestive cardiac failure ≥ NYHA grade 2.
9. 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.
10. Active inflammatory bowel disease or other colorectal diseases that lead to chronic diarrhea.
11. Suspected autoimmune disease.
12. Interstitial lung disease, non-infectious pneumonia or uncontrollable systemic diseases (such as diabetes, hypertension, pulmonary fibrosis and acute pneumonia).
13. Suspected allergic to any drugs used in the trial.
14. History of any immune checkpoint inhibitor therapy.
15. Clinically detectable second primary malignancy, or history of other malignancies within 5 years.
16. Pregnant or lactating women or women who may be pregnant have a positive pregnancy test before the first medication; Or the female participants themselves and their partners who were unwilling to implement strict contraception during the study period.
17. The investigator considers that the subject is not suitable to participate in this clinical study due to any clinical or laboratory abnormalities or compliance problems.
18. Serious mental abnormalities.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Group A; 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); PD-1 antibody: (Toripalimab): 240mg q3w; Drug: Capecitabine; Capecitabine:1000mg/m² d1-14 q3w; Capecitabine:825mg/m² on the day of radiotherapy; Drug: Oxaliplatin; 130 mg/m² q3w; Drug: Irinotecan; 200 mg/m² q3w; Radiation: Radiation; 45-50Gy/25Fx or 30Gy/15Fx; Procedure: surgery; The type of surgery will depend on the site of recurrence and the involvement of adjacent structures, which will be determined by the surgeons.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
R0 resection rate	Complete resection rate, defined as no residual tumor cells at the surgical margin under the microscope or the naked eye.	up to 1 year
3-year Progression-Free Survival	Defined as the time from the date of start treatment until the date of local recurrence or local recurrence progression or distant metastases or death from any cause or censored at last follow-up within 3 years.	up to 3 years
Overall Survival	Defined as the time from the date of start treatment until the date of death from any cause or censored at last follow-up.	up to 3 years
Pathological tumor regression grading	Classify according to the Mandard tumor regression grading system.	up to 1 year
Operation complications	intraoperative complications	up to 1 year
Incidence of major surgical complications	From the date of surgery to 3 months after surgery, according to Clavien-Dindo classification score.	up to 3 months

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Estimated): January 1, 2025
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): December 31, 2028

Study Registration Dates

• First Submitted: December 19, 2024
• First Submitted That Met QC Criteria: December 24, 2024
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: December 24, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Keywords: locally recurrent rectal cancer; PD-1 inhibitor; preoperative chemoradiotherapy
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Site; Neoplasms; Disease Attributes; Intestinal Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colorectal Neoplasms; Intestinal Neoplasms; Rectal Diseases; Rectal Neoplasms; Recurrence; Antineoplastic Agents; Immunologic Factors; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Topoisomerase I Inhibitors; Topoisomerase Inhibitors; Capecitabine; Oxaliplatin; Irinotecan; Antibodies
• Other Study ID Numbers: 2024ZSLYEC-684

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No