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

NCT ID: NCT06872606

Last Updated: 2025-03-12

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 33 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-04-01
• Study Completion Date: 2028-04-01

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

POBTAS Trial Arm

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.

Group Type: EXPERIMENTAL

Pucotenlimab

Intervention Type: DRUG

Pucotenlimab (200 mg IV, q3w)

Bevacizumab

Intervention Type: DRUG

Bevacizumab (7.5 mg/kg IV, q3w)

Oxaliplatin

Intervention Type: DRUG

Oxaliplatin (130 mg/m² IV, q3w)

Trifluridine/Tipiracil Hydrochloride

Intervention Type: DRUG

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

Short-course radiotherapy

Intervention Type: RADIATION

(25 Gy/5 fractions)

intracavitary brachytherapy

Intervention Type: RADIATION

brachytherapy (3 Gy/3 fractions).

Interventions

Pucotenlimab

Pucotenlimab (200 mg IV, q3w)

Intervention Type: DRUG

Bevacizumab

Bevacizumab (7.5 mg/kg IV, q3w)

Intervention Type: DRUG

Oxaliplatin

Oxaliplatin (130 mg/m² IV, q3w)

Intervention Type: DRUG

Trifluridine/Tipiracil Hydrochloride

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

Intervention Type: DRUG

Short-course radiotherapy

(25 Gy/5 fractions)

Intervention Type: RADIATION

intracavitary brachytherapy

brachytherapy (3 Gy/3 fractions).

Intervention Type: RADIATION

Eligibility Criteria

Inclusion Criteria

1. Patients who are willing to receive neoadjuvant therapy.

2. ≧18 years old.

3. 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.

4. Histologically diagnosed as rectal adenocarcinoma.

5. Clinical stage: cT2-4a N+ or cT3/T4a N0 (MRI/CT-confirmed).

6. MSS/pMMR status confirmed by immunohistochemistry or PCR before treatment .

7. ECOG Scale of Performance Status score 0-1 point.

8. Adequate organ function (hematologic, hepatic, renal).

9. Have not received anti-tumor and immunotherapy before enrollment.

10. Laboratory inspections must meet the following standards:

1) 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.

11. Voluntarily participate in this study and sign the informed consent.

Exclusion Criteria

1. History of other malignant diseases in the past 5 years.

2. Patients with metastases from other sites (stage IV patients).

3. Patients withT4b or positive lateral lymph nodes by pelvic contrast-enhanced CT and pelvic high-resolution MRI.

4. Patients with intestinal obstruction, intestinal perforation, intestinal bleeding, etc. requiring emergency surgery.

5. Known allergic to oxaliplatin, PD-1 monoclonal antibody and other intervention drugs.

6. Pathologically suggested signet ring cell carcinoma and mucinous adenocarcinoma.

7. dMMR or MSI-H patients.

8. 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.

9. 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.

10. Active autoimmune disease that may worsen while receiving immunostimulants.

11. Known history of positive HIV test or known acquired immunodeficiency syndrome.

12. Patients who are using immunosuppressive agents, except for the following conditions:

1) 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.

15. Vulnerable groups, including mentally ill, cognitively impaired, critically ill patients, minors, etc.

16. Other conditions that the investigator judges that the patient is not suitable to participate in the clinical study, etc.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sir Run Run Shaw Hospital

OTHER

Sponsor Role: lead

Responsible Party

Sheng Dai

Director, Medical affairs department

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Sir Run Run Shaw Hospital, Zhejiang University School of Medicine

Hangzhou, Zhejiang, China

Countries

China

Central Contacts

Sheng Dai, MD & PHD

Role: CONTACT

daimd@zju.edu.cn

+86-13575472669

Facility Contacts

Xiujun Cai

Role: primary

cxjzu@hotmail.com

+86-057186090073

Other Identifiers

2024-0623

Identifier Type: -

Identifier Source: org_study_id