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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| POBTAS Trial Arm | Experimental | Intervention: 1.Radiotherapy:
Administered during weeks 5-6, targeting residual lesions with 3Gy X 3F, completed within 1 week. 2.Systemic Therapy Post-Initial Radiotherapy:
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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Pucotenlimab | Drug | Pucotenlimab (200 mg IV, q3w) |
| |
| Bevacizumab |
| Measure | Description | Time Frame |
|---|---|---|
| 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) |
| Measure | Description | Time Frame |
|---|---|---|
| Total mesorectal excision rate | Population who not achieve complete clinical response and have TME surgery after total neoadjuvant therapy | After 2 weeks (once biopsy or local excision is done) |
| Total mesorectal excision rate after recurrence |
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Inclusion Criteria:
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) 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.
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Sheng Dai, MD & PHD | Contact | +86-13575472669 | daimd@zju.edu.cn |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Sir Run Run Shaw Hospital, Zhejiang University School of Medicine | Hangzhou | Zhejiang | 310016 | China |
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| Drug |
Bevacizumab (7.5 mg/kg IV, q3w) |
|
| Oxaliplatin | Drug | Oxaliplatin (130 mg/m² IV, q3w) |
|
| Trifluridine/Tipiracil Hydrochloride | Drug | TAS-102 (25 mg/m² orally, days 1-5 and 8-12). |
|
| Short-course radiotherapy | Radiation | (25 Gy/5 fractions) |
|
| intracavitary brachytherapy | Radiation | brachytherapy (3 Gy/3 fractions). |
|
Population who recurrent and have Salvage total mesorectal excision after achieving complete clinical response after total neoadjuvant therapy
| Through study completion, an average of 3 year |
| Tumor regression grade | Tumor Regression Grade(TRG)will be done via pathologic assessment on the surgical specimen with AJCC/CAP TRG system | After 2 weeks (once biopsy or local excision is done) |
| Overall survival | The proportion of participants who remain survival at 3 years | Up to 3 years |
| Progression free survival | The proportion of participants who remain progression free at 3 years | Up to 3 years |
| TRAEs | Number of participants with treatment-related adverse events as assessed by NCI-CTCAE v5.0 | Up to 3 years |
| Surgical Complications | Surgical Complications of biopsy, local excision or total mesorectal resection procedure for patients as assessed by Clavien-Dindo classification. | Up to 3 years |
| QoL | Quality of life of the patients in total neoadjuvant settings as assessed by Functional Assessment of Cancer Therapy - Colorectal (FACT-C) questionnaire liscenced from The Functional Assessment of Chronic Illness Therapy System ("FACIT System"). By using the Manual scoring template, some items are reverse scored. Subscale scores, total scores and TOI scores. The higher the score, the better the QOL. | Up to 3 years |
| ID | Term |
|---|---|
| D012004 | Rectal Neoplasms |
| ID | Term |
|---|---|
| D015179 | Colorectal Neoplasms |
| D007414 | Intestinal Neoplasms |
| D005770 | Gastrointestinal Neoplasms |
| D004067 | Digestive System Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D004066 | Digestive System Diseases |
| D005767 | Gastrointestinal Diseases |
| D007410 | Intestinal Diseases |
| D012002 | Rectal Diseases |
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| ID | Term |
|---|---|
| D000068258 | Bevacizumab |
| D000077150 | Oxaliplatin |
| D014271 | Trifluridine |
| D001918 | Brachytherapy |
| ID | Term |
|---|---|
| D061067 | Antibodies, Monoclonal, Humanized |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
| D056831 | Coordination Complexes |
| D009930 | Organic Chemicals |
| D013936 | Thymidine |
| D011741 | Pyrimidine Nucleosides |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D003853 | Deoxyribonucleosides |
| D009705 | Nucleosides |
| D009706 | Nucleic Acids, Nucleotides, and Nucleosides |
| D011878 | Radiotherapy |
| D013812 | Therapeutics |
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