Total Neoadjuvant Chemoradiotherapy Plus Anti-PD-1 in Subperitoneal Patients With Locally Advanced Rectal CancerPatients With Locally Advanced Rectal Cancer: A Prospective, Single Arm, Exploratory Study

• ClinicalTrials.gov Identifier: NCT05998122
• Recruitment Status: Not yet recruiting
• First Posted: August 18, 2023
• Last Update Posted: August 18, 2023
• Sponsor: The First Hospital of Jilin University
• Information provided by (Responsible Party): Quan Wang, The First Hospital of Jilin University

Tracking Information

• First Submitted Date: August 11, 2023
• First Posted Date: August 18, 2023
• Last Update Posted Date: August 18, 2023
• Estimated Study Start Date: September 1, 2023
• Estimated Primary Completion Date: December 31, 2026 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 11, 2023)

Complete response rate (CR) [ Time Frame: Within one week after Last treatment ]

defined as clinical complete response (cCR) or pathologic complete response (pCR) achieved after neoadjuvant therapy.

• Original Primary Outcome Measures: Same as current
• Change History: No Changes Posted

Current Secondary Outcome Measures (submitted: August 11, 2023)

• Disease-Free Survival (DFS) [ Time Frame: 1/2/3 years from the date of receiving neoadjuvant therapy ]
  1/2/3 years disease-free survival
• Recurrence -Free Survival (RFS) [ Time Frame: 1/2/3 years from the date of receiving neoadjuvant therapy ]
  1/2/3 years recurrence -free survival
• Overall Survival (OS) [ Time Frame: 3 years from the date of receiving neoadjuvant therapy ]
  3 years overall survival
• Local Recurrence (LR) Rate [ Time Frame: 2 years from the date of receiving neoadjuvant therapy ]
  2-year local recurrence rate
• Organ preservation rate [ Time Frame: 1/2/3 years from the date of receiving neoadjuvant therapy ]
  Organ preservation rate
• R0 Resection rate [ Time Frame: Within one week after surgery ]
  R0 Resection rate
• The incidence of serious adverse events [ Time Frame: Within 3 months after Last medication ]
  Any treatment-related grade 3 or higher non-hematological adverse event determined by CTCAE version v 5.0.
• QLQ-C30 score [ Time Frame: up to 12 months ]
  Quality of Life Questionnaire C30
• QLQ-C29 score [ Time Frame: up to 12 months ]
  Quality of Life Questionnaire C29
• Low Anterior Resection Syndrome (LARS) [ Time Frame: up to 12 months ]
  Low Anterior Resection Syndrome Questionnaire
• Quality of life and function assessment [ Time Frame: up to 12 months ]
  IIEF-5 (international questionnaire of erectile function-5)score
• Wexner score [ Time Frame: up to 12 months ]
  Wexner incontinence score

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Total Neoadjuvant Chemoradiotherapy Plus Anti-PD-1 in Subperitoneal Patients With Locally Advanced Rectal CancerPatients With Locally Advanced Rectal Cancer: A Prospective, Single Arm, Exploratory Study
• Official Title: Total Neoadjuvant Chemoradiotherapy Plus Anti-PD-1 in Subperitoneal High-Risk or Very High-Risk Patients With Locally Advanced Rectal Cancer: A Prospective, Single Arm, Exploratory Study
• Brief Summary: Previously, preliminary results, from a subgroup analysis of STARS-RC03 (NCT04906044) conducted by our research team, showed that the 6-cycles consolidation chemotherapy combining with anti-PD-1 therapy had a better tumor regression advantage with a restricted safety profile contrasted with 3-cycle counterparts. Herein, we designed this study to further evaluate the short-term efficacy (such as pCR rate, R0 resection rate, etc.) and long-term survival (including DFS, OS, etc.) of 6-cycles consolidation therapy.
• Detailed Description: The combination of total neoadjuvant treatment (TNT) and immunotherapy has shown a significant improvement in the pCR rate compared to the standard of care (SOC) or TNT alone for pMMR LARC. On this basis, we believe that this treatment mode will offers the opportunity of organ preservation for subperitoneal "Bad" or "Advanced" patients with LARC, who are initially assessed as unresectable or difficult to obtain R0 resection. Previously, preliminary results, from a subgroup analysis of STARS-RC03 (NCT04906044) conducted by our research team, showed that the 6-cycles consolidation chemotherapy combining with anti-PD-1 therapy had a better tumor regression advantage with a restricted safety profile contrasted with 3-cycle counterparts. Herein, we designed this study to further evaluate the short-term efficacy (such as pCR rate, R0 resection rate, etc.) and long-term survival (including DFS, OS, etc.) of 6-cycles consolidation therapy.
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Locally Advanced Rectal Cancer
• Total Neoadjuvant Treatment
• Anti-PD-1

Intervention

Other: nCRT → (CapeOX+Sintilimab)×6 → Surgery/W&W

Radiation: Long-course chemoradiotherapy is delivered in 50 Gy/25 fractions with concurrent Capecitabine (825mg/m2, P.O. Bid, 5d/w).

Drug: CapeOX (Capecitabine 1000mg/m2, P.O. Bid, d1-d14, q3w; Oxaliplatin 130mg/m2, i.v., d1, q3w), and Sintilimab (200mg, i.v. , d1).

Surgical Approach: TME surgery, The surgical approach can be open, laparoscopic or robotic depending on the patient.

Study Arms

Experimental: Experimental

Radiation: Long-course chemoradiotherapy is delivered in 50 Gy/25 fractions with concurrent Capecitabine (825mg/m2, P.O. Bid, 5d/w).

Drug: CapeOX (Capecitabine 1000mg/m2, P.O. Bid, d1-d14, q3w; Oxaliplatin 130mg/m2, i.v., d1, q3w), and Sintilimab (200mg, i.v. , d1).

Surgical Approach: TME surgery, The surgical approach can be open, laparoscopic or robotic depending on the patient.

Intervention: Other: nCRT → (CapeOX+Sintilimab)×6 → Surgery/W&W

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Not yet recruiting
• Estimated Enrollment (submitted: August 11, 2023): 45
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 31, 2028
• Estimated Primary Completion Date: December 31, 2026 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. The patients and their families are able to understand and are willing to participate in this clinical study, and sign an informed consent form.
2. Age: 18~75 years old, no gender limit;
3. Pathologically diagnosed rectal adenocarcinoma: differentiated into Grade 1-3, that is, high, medium, and poorly differentiated tubular adenocarcinoma; classified as pMMR/MSS.
4. The initial TNM risk category (from Rectal cancer: ESMO Clinical Practice Guidelines, 2017 edition) is as follows: 1) "Bad": cT3c/d or very low localisation levators threatened, MRF clear; cT3c/d mid-rectum, cN1-N2 (extranodal), EMVI+, limited cT4aN0; 2) "Advanced": cT3 with any MRF involved, any cT4a/b, lateral node+.
5. The lower edge of the tumor is located below the peritoneal reflex;
6. No distant transfer;
7. ECOG PS score 0-1 within 7 days before the first medication;
8. Hepatitis B Surface Antigen (HBsAg) (-) and Hepatitis B Core Antibody (HBcAb) (-). If HBsAg (+) or HBcAb (+), hepatitis B virus deoxyribonucleic acid (HBV-DNA) must be less than 1000 copies/mL or 200 IU/mL before entering the group.
9. HCV antibody (-)
10. The main organ function is normal.
11. No history of pelvic radiotherapy;
12. No history of rectal cancer surgery or chemotherapy;
13. Not accompanied by systemic infections requiring antibiotic treatment;
14. Heart, lung, liver, and kidney functions can tolerate surgery;
15. Others, based on the results of previous medical history, vital signs, physical examination or laboratory examination, the research doctor judges that you are suitable for participating in this clinical study.

Exclusion Criteria:

1. Recurrent rectal cancer;
2. Patients who are planning to undergo or have previously received organ or bone marrow transplantation;
3. Myocardial infarction or poorly controlled arrhythmia (including QTc interval ≥ 450 ms for males and ≥ 470 ms for females) occurred within 6 months before the first medication (QTc interval is calculated by Fridericia formula);
4. Existence of NYHA standard grade III to IV cardiac insufficiency or color Doppler ultrasound examination: LVEF (left ventricular ejection fraction) <50%;
5. Human immunodeficiency virus (HIV) infection;
6. Suffer from active tuberculosis;
7. Past and present patients with interstitial pneumonia, pneumoconiosis, radiation pneumonia, drug-related pneumonia, severely impaired lung function, etc., which may interfere with the detection and treatment of suspected drug-related lung toxicity;
8. Patients with active or suspicious autoimmune disease, or with a history of that;
9. Received treatment with live vaccines within 28 days before the first administration; except for inactivated viral vaccines for seasonal influenza;
10. Have received other antibody/drug treatments against immune checkpoints in the past, such as PD-1, PD-L1, CTLA4, etc.;
11. Known to have a history of severe allergies to any monoclonal antibody or research drug excipients;
12. In the past 5 years, patients have suffered from malignant tumors whose survival rate is significantly lower than the historical data of our rectal cancer survival rate (properly treated basal cell carcinoma, skin squamous cell carcinoma, small kidney cancer, breast cancer, and papillary thyroid carcinoma are not included here. range);
13. The patient has had arterial embolism diseases in the past 6 months, such as angina pectoris, MI, TIA, CVA, etc.;
14. Have received other types of anti-tumor or experimental treatments;
15. The patient is a female during pregnancy or lactation;
16. The patient has other diseases or abnormal mental states, which may affect the patient's participation in this study;
17. There are patients who may increase the risk of participating in research and research medication, or other severe, acute and chronic diseases, who are not suitable for clinical research based on the judgment of the investigator.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 75 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Wang Quan, Prof.; +86-431-81875602; wquan@jlu.edu.cn

Contact: PengYu Chang, Prof.; changpengyu@mails.jlu.edu.cn

• Listed Location Countries: China

Administrative Information

• NCT Number: NCT05998122
• Other Study ID Numbers: STARS-RC06
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Undecided

• Current Responsible Party: Quan Wang, The First Hospital of Jilin University
• Original Responsible Party: Same as current
• Current Study Sponsor: The First Hospital of Jilin University
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: The First Hospital of Jilin University
• Verification Date: August 2023