search
Back to results

Total Neoadjuvant Therapy With Short-course Radiation Followed by Envafolimab Plus CAPEOX for MSS Locally Advanced Ultra Low Rectal Adenocarcinoma (RECMULRA-TNT)

Primary Purpose

Rectal Cancer

Status
Recruiting
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
Envafolimab
Sponsored by
Sir Run Run Shaw Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Rectal Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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. The clinical staging by pelvic contrast-enhanced CT and pelvic high-resolution MRI were stage I, II and III. MMR protein detection or MSI gene detection of rectal cancer specimens confirmed pMMR or MSS before treatment . The patient is difficult cured by anal reserve procedure based on the primary physician's practice. The patient has good compliance and can come to the hospital for re-examination as required. ECOG Scale of Performance Status score 0-1 point. 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. 12. 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 with 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, capecitabine, PD-L1 monoclonal antibody and other 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.

Sites / Locations

  • Sir Run Run Shaw Hospital, Zhejiang University School of MedicineRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Total Neoadjuvant Therapy with Short-course Radiation followed by Envafolimab plus CAPEOX

Arm Description

The enrolled patients with MSS-type advanced ultra low rectal cancer will receive a combined regimen of neoadjuvant chemoradiotherapy combined with immunotherapy and biopsy or local excision. Radiotherapy uses a short-range mode, irradiating the primary tumor and high-risk areas with dose of 25 Gy. After radiotherapy, PD-L1 antibody (150mg/week, subcutaneous injection × 24 weeks) immunotherapy combined with 8 courses of CAPEOX chemotherapy was performed. Two weeks after the end of the combined treatment plan in step 2), biopsy or local excision of the lesion is performed.

Outcomes

Primary Outcome Measures

Organ reservation rate
population who achieve complete clinical response after total neoadjuvant therapy

Secondary Outcome Measures

Total mesorectal excision rate
population who not achieve complete clinical response after total neoadjuvant therapy
Total mesorectal excision rate after recurrence
population who recurrent and have Salvage total mesorectal excision after achieving complete clinical response after total neoadjuvant therapy
Tumor regression grade f
Tumor regression grade following short-course radiation then Envafolimab Plus CAPEOX as assessed by AJCC/CAP TRG system
Overall survival
The proportion of participants who remain survival at 3 years
Progression free survival
The proportion of participants who remain progression free at 3 years
TRAEs
Number of participants with treatment-related adverse events as assessed by NCI-CTCAE v5.0
Surgical Complications
Surgical Complications of biopsy, local excision or total mesorectal resection procedure for patients after short-course radiation then Envafolimab Plus CAPEOX as assessed by Clavien-Dindo classification
QoL
Quality of life of the patients in total neoadjuvant settings of short-course radiation followed with Envafolimab Plus CAPEOX 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.

Full Information

First Posted
May 4, 2023
Last Updated
May 4, 2023
Sponsor
Sir Run Run Shaw Hospital
search

1. Study Identification

Unique Protocol Identification Number
NCT05858567
Brief Title
Total Neoadjuvant Therapy With Short-course Radiation Followed by Envafolimab Plus CAPEOX for MSS Locally Advanced Ultra Low Rectal Adenocarcinoma
Acronym
RECMULRA-TNT
Official Title
Total Neoadjuvant Therapy With Short-course Radiation Followed by Envafolimab Plus CAPEOX for MSS Locally Advanced Ultra Low Rectal Adenocarcinoma: An Prospective, Single Center, Single Arm Study
Study Type
Interventional

2. Study Status

Record Verification Date
May 2023
Overall Recruitment Status
Recruiting
Study Start Date
May 11, 2023 (Anticipated)
Primary Completion Date
December 31, 2024 (Anticipated)
Study Completion Date
June 30, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Sir Run Run Shaw Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
Short-course radiotherapy combined with immunotherapy may bring revolutionary changes to the total neoadjuvant therapy mode for locally advanced ultra low rectal cancer to preserve the organs. In view of the shortcomings of the current otal neoadjuvant therapy model for locally advanced ultra low rectal cancer, we will explore the feasibility of a new model of short-course radiotherapy combined with immunotherapy, and develop a possible optimal plan based on the existing theoretical basis, namely "short-course radiotherapy + PD-L1 monoclonal antibody combined with CAPEOX chemotherapy for 8 cycles", and explore the efficacy and adverse effects of this model. The study will also attempt to explore the characteristics of the treatment beneficiary population, explore the characteristics of the treatment beneficiary population by multi-dimensional tumor and microenvironmental information through multi-omics sequencing analysis, attempt to build an efficacy prediction model, early screening of the treatment beneficiary population for precise treatment, and thus explore a new model of radiotherapy combined with immunotherapy for the poplation who can be achieved organ preservation.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Rectal Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
30 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Total Neoadjuvant Therapy with Short-course Radiation followed by Envafolimab plus CAPEOX
Arm Type
Experimental
Arm Description
The enrolled patients with MSS-type advanced ultra low rectal cancer will receive a combined regimen of neoadjuvant chemoradiotherapy combined with immunotherapy and biopsy or local excision. Radiotherapy uses a short-range mode, irradiating the primary tumor and high-risk areas with dose of 25 Gy. After radiotherapy, PD-L1 antibody (150mg/week, subcutaneous injection × 24 weeks) immunotherapy combined with 8 courses of CAPEOX chemotherapy was performed. Two weeks after the end of the combined treatment plan in step 2), biopsy or local excision of the lesion is performed.
Intervention Type
Drug
Intervention Name(s)
Envafolimab
Intervention Description
Drug: Envafolimab This product is administered by subcutaneous injection. The recommended dose of subcutaneous injection is 150 mg, administered weekly (QW). Other Names: KN053 Drug: Oxaliplatin 130mg/m2,ivgtt,d1 Drug: Capecitabine 1000mg/m2,po,bid,d1-14 Radiation: Short-course Radiation Short-course radiotherapy, using three-dimensional conformal or intensity-modulated radiotherapy, the dose is divided into 5Gy/f, the total dose is 25Gy/5f, 1f/d, and the irradiation is completed within 7 days. Procedure/Surgery: Biopsy, local excision or TME surgery (total mesorectal excision) Biopsy can choose endoscopic or needle biopsy, colcal excision refers to excison of the local lession after total neoadjuvant therapy The total mesorectal excision can choose open, laparoscopic or robotic according to the specific condition of the patient.
Primary Outcome Measure Information:
Title
Organ reservation rate
Description
population who achieve complete clinical response after total neoadjuvant therapy
Time Frame
After 2 weeks (once biopsy or local excision is done)
Secondary Outcome Measure Information:
Title
Total mesorectal excision rate
Description
population who not achieve complete clinical response after total neoadjuvant therapy
Time Frame
After 2 weeks (once biopsy or local excision is done)
Title
Total mesorectal excision rate after recurrence
Description
population who recurrent and have Salvage total mesorectal excision after achieving complete clinical response after total neoadjuvant therapy
Time Frame
from primary evaluation at 2 weeks after total neoadjuvant therapy finished
Title
Tumor regression grade f
Description
Tumor regression grade following short-course radiation then Envafolimab Plus CAPEOX as assessed by AJCC/CAP TRG system
Time Frame
After 2 weeks (once biopsy or local excision is done)
Title
Overall survival
Description
The proportion of participants who remain survival at 3 years
Time Frame
Up to 3 years
Title
Progression free survival
Description
The proportion of participants who remain progression free at 3 years
Time Frame
Up to 3 years
Title
TRAEs
Description
Number of participants with treatment-related adverse events as assessed by NCI-CTCAE v5.0
Time Frame
Up to 3 years
Title
Surgical Complications
Description
Surgical Complications of biopsy, local excision or total mesorectal resection procedure for patients after short-course radiation then Envafolimab Plus CAPEOX as assessed by Clavien-Dindo classification
Time Frame
Up to 3 years
Title
QoL
Description
Quality of life of the patients in total neoadjuvant settings of short-course radiation followed with Envafolimab Plus CAPEOX 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.
Time Frame
Up to 3 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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. The clinical staging by pelvic contrast-enhanced CT and pelvic high-resolution MRI were stage I, II and III. MMR protein detection or MSI gene detection of rectal cancer specimens confirmed pMMR or MSS before treatment . The patient is difficult cured by anal reserve procedure based on the primary physician's practice. The patient has good compliance and can come to the hospital for re-examination as required. ECOG Scale of Performance Status score 0-1 point. 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. 12. 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 with 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, capecitabine, PD-L1 monoclonal antibody and other 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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
sheng dai, MD&PhD
Phone
13575472669
Email
daimd@zju.edu.cn
Facility Information:
Facility Name
Sir Run Run Shaw Hospital, Zhejiang University School of Medicine
City
Hangzhou
State/Province
Zhejiang
ZIP/Postal Code
310016
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Xiujun Cai

12. IPD Sharing Statement

Plan to Share IPD
Undecided

Learn more about this trial

Total Neoadjuvant Therapy With Short-course Radiation Followed by Envafolimab Plus CAPEOX for MSS Locally Advanced Ultra Low Rectal Adenocarcinoma

We'll reach out to this number within 24 hrs