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

Официальное название

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）

Обзор

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.

Вмешательства

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

Первичные конечные точки

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

Вторичные конечные точки (8)

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

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

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

Идентификаторы

NCT: NCT06872606 · 2024-0623

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗