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

Official title

The Efficacy and Safety of 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 Adenocarcinoma: an Prospective, Single Arm Clinical Trial （SCRIPBOT Trial）

Overview

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.

Interventions

• Drug Pucotenlimab
  Pucotenlimab (200 mg IV, q3w)
• Drug Bevacizumab
  Bevacizumab (7.5 mg/kg IV, q3w)
• Drug Oxaliplatin
  Oxaliplatin (130 mg/m² IV, q3w)
• Drug Trifluridine/Tipiracil Hydrochloride
  TAS-102 (25 mg/m² orally, days 1-5 and 8-12).
• Radiation Short-course radiotherapy
  (25 Gy/5 fractions)
• Radiation intracavitary brachytherapy
  brachytherapy (3 Gy/3 fractions).

Primary outcome measures

• Organ preservation rate [Time frame: Up to 2 weeks (once evaluation or biopsy is done)]

Secondary outcome measures (8)

• Total mesorectal excision rate [Time frame: After 2 weeks (once biopsy or local excision is done)]
• Total mesorectal excision rate after recurrence [Time frame: Through study completion, an average of 3 year]
• Tumor regression grade [Time frame: After 2 weeks (once biopsy or local excision is done)]
• Overall survival [Time frame: Up to 3 years]
• Progression free survival [Time frame: Up to 3 years]
• TRAEs [Time frame: Up to 3 years]
• Surgical Complications [Time frame: Up to 3 years]
• QoL [Time frame: Up to 3 years]

Eligibility criteria

Inclusion criteria

• 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:

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

• 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:

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Sir Run Run Shaw Hospital, Zhejiang University School of Medicine — Hangzhou

Identifiers

NCT: NCT06872606 · 2024-0623

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗