Preoperative Chemoradiotherapy and Toripalimab in Locally Recurrent Rectal Cancer

Phase 2

Not yet recruiting

• Conditions: Recurrent Rectal Cancer
• Interventions: Drug: PD-1 antibody (Toripalimab); Drug: Capecitabine; Drug: Oxaliplatin; Drug: Irinotecan; Radiation: Radiation; Procedure: surgery

• Registration Number: NCT06751394
• Lead Sponsor: Sixth Affiliated Hospital, Sun Yat-sen University

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.

Detailed Description

Not available

Study Timeline

• Status Verified: 2024-12
• Study First Submitted: 2024-12-19
• Study First Submitted QC: 2024-12-24
• Last Update Submitted: 2024-12-24
• Study First Posted: 2024-12-27
• Last Update Posted: 2024-12-27
• Study Start: 2025-01-01
• Primary Completion: 2028-12-31
• Study Completion: 2028-12-31

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 44

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Group A	PD-1 antibody (Toripalimab)	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.
Group A	Capecitabine	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.
Group A	Oxaliplatin	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.
Group A	Irinotecan	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.
Group A	Radiation	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.
Group A	surgery	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.

Primary Outcome Measures

Name	Time	Method
Pathological complete response rate	up to 1 year	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.

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Sixth Affiliated Hospital, Sun Yat-sen University; 🇨🇳 Guangzhou, Guangdong, China