Short-Course Radiotherapy Combined with Intracavitary Brachytherapy Followed by Pucotenlimab, Bevacizumab, Oxaliplatin, and Trifluridine/Tipiracil (TAS-102) for Total Neoadjuvant Therapy of Microsatellite Stable (MSS) Locally Advanced Low Rectal Cancer

NCT06872606 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: 2024-0623
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 1

Brief Summary

A Prospective Single-Arm Study of Short-Course Radiotherapy Followed by PD-1 Monoclonal Antibody, Bevacizumab, Oxaliplatin, and Trifluridine/Tipiracil for Total Neoadjuvant Therapy in MSS Locally Advanced Low Rectal Cancer. This is a Non-Randomized, Single Group Assignment, Open Label, Phase: Phase II study. The Primary Objective is to assess the organ preservation rate (clinical complete response, cCR) after total neoadjuvant therapy. Secondary Objectives are Tumor regression grade (TRG), 3-year overall survival (OS) and disease-free survival (DFS), and Safety and quality of life (QoL). In this study, the investigators will perform the multi-dimensional omics study to explore the tumors microenvironments, explore the characteristics of the treatment benefit population, and try to construct an efficacy prediction model to screen the treatment benefit population early and implement precise treatment.

Conditions

Rectal Adenocarcinoma

Keywords

Short-Course Radiotherapy; Pucotenlimab; Oxaliplatin; Bevacizumab; Trifluridine/Tipiracil（TAS-102）

Outcome Measures

Primary Outcomes (1)

• Organ preservation rate

  The organ preservation rate was calculated as the percentage of participants who achieved cCR and were spared from total mesorectal excision (TME) surgery relative to the total study cohort. Clinical complete response (cCR) requires both histopathological confirmation (no viable tumor cells in biopsy specimens) and radiographic confirmation (absence of tumor on CT, MRI, or PET-CT).

  Up to 2 weeks (once evaluation or biopsy is done)

Secondary Outcomes (8)

• Total mesorectal excision rate

  After 2 weeks (once biopsy or local excision is done)

• Total mesorectal excision rate after recurrence

  Through study completion, an average of 3 year

• Tumor regression grade

  After 2 weeks (once biopsy or local excision is done)

• Overall survival

  Up to 3 years

• Progression free survival

  Up to 3 years

Study Arms (1)

POBTAS Trial Arm

EXPERIMENTAL

Intervention: 1.Radiotherapy: 1. Phase 1 (Short-Course External Radiotherapy): Intensity-modulated radiotherapy (IMRT) at 5 Gy X 5F, completed within 1 week. 2. Phase 2 (Intracavitary Brachytherapy): Administered during weeks 5-6, targeting residual lesions with 3Gy X 3F, completed within 1 week. 2.Systemic Therapy Post-Initial Radiotherapy: 1. Cycles 1-2: PD-1 antibody immunotherapy (pucotenlimab) combined with bevacizumab, oxaliplatin, and trifluridine/tipiracil (TAS-102). 2. Cycles 3-4: Sequential PD-1 immunotherapy + oxaliplatin + TAS-102 (bevacizumab omitted in Cycle 4). 3.Post-Cycle 4 Evaluation: If ypT0 (local pathological complete response): Enter follow-up observation. If non-CR: Proceed to Step 4. 4.Extended Systemic Therapy for Non-CR Patients: Cycles 5-8: Repeat PD-1 immunotherapy + bevacizumab + oxaliplatin + TAS-102 (bevacizumab omitted in Cycle 8). 5.Post-Cycle 8 Evaluation: If ypT0: Enter follow-up observation. If non-ypT0: Proceed to TME surgery.

Drug: Pucotenlimab; Drug: Bevacizumab; Drug: Oxaliplatin; Drug: Trifluridine/Tipiracil Hydrochloride; Radiation: Short-course radiotherapy; Radiation: intracavitary brachytherapy

Interventions

Pucotenlimab DRUG

Pucotenlimab (200 mg IV, q3w)

POBTAS Trial Arm

Bevacizumab DRUG

Bevacizumab (7.5 mg/kg IV, q3w)

POBTAS Trial Arm

Oxaliplatin DRUG

Oxaliplatin (130 mg/m² IV, q3w)

POBTAS Trial Arm

Trifluridine/Tipiracil Hydrochloride DRUG

TAS-102 (25 mg/m² orally, days 1-5 and 8-12).

POBTAS Trial Arm

Short-course radiotherapy RADIATION

(25 Gy/5 fractions)

POBTAS Trial Arm

intracavitary brachytherapy RADIATION

brachytherapy (3 Gy/3 fractions).

POBTAS Trial Arm

Eligibility Criteria

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

You may qualify if:

• Patients who are willing to receive neoadjuvant therapy.
• ≧18 years old.
• Diagnosed by digital rectal examination, colonoscopy, and high-resolution MRI of the pelvis, the tumor is less than or equal to 5 cm from the anus.
• Histologically diagnosed as rectal adenocarcinoma.
• Clinical stage: cT2-4a N+ or cT3/T4a N0 (MRI/CT-confirmed).
• MSS/pMMR status confirmed by immunohistochemistry or PCR before treatment .
• ECOG Scale of Performance Status score 0-1 point.
• Adequate organ function (hematologic, hepatic, renal).
• Have not received anti-tumor and immunotherapy before enrollment.
• Laboratory inspections must meet the following standards:
• \) White blood cell count\>3.5×109/L, absolute value of neutrophils\>1.8×109/L, platelet count ≥75×109/L, hemoglobin ≥100g/L; 2) INR≤1.5, and APTT≤1.5 times the upper limit of normal or partial prothrombin time (PT) ≤1.5 times the upper limit of normal; 3) Total bilirubin ≤ 1.25 times the upper limit of normal; ALT and AST \< 5 times the upper limit of normal; 4) 24h creatinine clearance \>50mL/min or serum creatinine \<1.5 times the upper limit of normal.
• \. Voluntarily participate in this study and sign the informed consent.

You may not qualify if:

• History of other malignant diseases in the past 5 years.
• Patients with metastases from other sites (stage IV patients).
• Patients withT4b or positive lateral lymph nodes by pelvic contrast-enhanced CT and pelvic high-resolution MRI.
• Patients with intestinal obstruction, intestinal perforation, intestinal bleeding, etc. requiring emergency surgery.
• Known allergic to oxaliplatin, PD-1 monoclonal antibody and other intervention drugs.
• Pathologically suggested signet ring cell carcinoma and mucinous adenocarcinoma.
• dMMR or MSI-H patients.
• The patient is accompanied by any unstable systemic disease, including but not limited to: severe infection, uncontrolled diabetes, hypertension uncontrolled by medication, unstable angina, cerebrovascular accident or transient cerebral ischemia, myocardial Infarction, congestive heart failure, severe cardiac arrhythmia requiring medication, hepatic, renal or metabolic disease; disease affecting the patient's life.
• The disease (such as mental illness, etc.) or condition (such as alcoholism or drug abuse, etc.) associated with the patient will increase the risk of the patient receiving the trial drug treatment or affect the patient's compliance with the trial requirements, or may confuse the research results.
• Active autoimmune disease that may worsen while receiving immunostimulants.
• Known history of positive HIV test or known acquired immunodeficiency syndrome.
• Patients who are using immunosuppressive agents, except for the following conditions:
• \) Intranasal, inhaled, topical steroids, or topical steroid injections (eg, intra-articular injections); 2) Physiological doses of systemic corticosteroids ≤10 mg/day prednisone or equivalent; 3) Steroids used to prevent allergic reactions (eg, before CT scan). 13. Received any other experimental drug treatment or participated in another interventional clinical trial within 30 days before screening 14. Women who are pregnant or breastfeeding or who plan to become pregnant or breastfeeding during the study period; men or women who are unwilling to take effective contraceptive measures.
• \. Vulnerable groups, including mentally ill, cognitively impaired, critically ill patients, minors, etc.
• \. Other conditions that the investigator judges that the patient is not suitable to participate in the clinical study, etc.

Sponsors & Collaborators

• Sir Run Run Shaw Hospital: lead

Study Sites (1)

Sir Run Run Shaw Hospital, Zhejiang University School of Medicine

Hangzhou, Zhejiang, 310016, China

Location

MeSH Terms

Conditions

Rectal Neoplasms

Interventions

Bevacizumab; Oxaliplatin; Trifluridine; Brachytherapy

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)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Coordination Complexes; Organic Chemicals; Thymidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Radiotherapy; Therapeutics

Central Study Contacts

Sheng Dai, MD & PHD

CONTACT

+86-13575472669; daimd@zju.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: Director, Medical affairs department

Study Record Dates

• First Submitted: March 5, 2025
• First Posted: March 12, 2025
• Study Start: April 1, 2025
• Primary Completion: April 1, 2026
• Study Completion (Estimated): April 1, 2028
• Last Updated: March 12, 2025

Record last verified: 2025-03

Locations

CN (1)