Back to resultsShort-course Radiotherapy Followed by Chemotherapy and PD-1 Inhibitor for Locally Advanced Rectal Cancer
Primary Purpose
Rectal Neoplasms Malignant, Radiotherapy
Status
Not yet recruiting
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
Sintilimab
Short-course radiotherapy
CAPOX/mFOLFOX
Sponsored by
About this trial
This is an interventional treatment trial for Rectal Neoplasms Malignant focused on measuring rectal cancer, short-course radiotherapy, total neoadjuvant therapy, PD-1 inhibitor
Eligibility Criteria
Inclusion Criteria:
- Biopsy proven rectal adenocarcinoma;
- Distance between tumour and anal verge≤ 10cm;
- Locally advanced tumour;(8th edition AJCC/UICC staging :cT3-T4N0/cT2-4N+，M0) Cancer Staging must be based on pelvic MRI or Endoscopic ultrasound;
- Eastern Cooperative Oncology Group(ECOG) performance score ≤ 1;
Mentally and physically fit for chemotherapy; Adequate blood counts: White blood cell count ≥3.5 x 109/L Haemoglobin levels ≥100g/L Platelet count ≥100 x 109/L Creatinine levels ≤1.0× upper normal limit（UNL） Urea nitrogen levels ≤1.0× upper normal limit（UNL） Alanine aminotransferase(ALT) ≤1.5× upper normal limit（UNL） Aspartate aminotransferase(AST) ≤1.5× upper normal limit（UNL） Alkaline phosphatase(ALP) ≤1.5× upper normal limit（UNL） Total bilirubin(TBIL)
≤1.5× upper normal limit（UNL）
- No excision of tumor, chemotherapy or other anti-tumor treatment after the diagnosis.
- No previous pelvic radiation history；
- Written informed consent;
Exclusion Criteria:
- Previous treatment with anti-PD-1/L1 and anti-CTLA-4 or other immune experimental drugs.
- Severe autoimmune disease: active inflammatory bowel disease (including Crohn's disease, ulcerative colitis), rheumatoid arthritis, scleroderma, systemic lupus erythematosus, autoimmune vasculitis (e.g. Wegener's granulomatosis)
- Symptomatic interstitial lung disease or active infectious/non-infectious pneumonia.
- At risk for bowel perforation: active diverticulitis, intra-abdominal abscess, gastrointestinal (GI) obstruction, abdominal cancer or other known risk factors for bowel perforation.
- history of other malignancies, excluding curable non-melanotic skin cancer and cervix carcinoma in situ；
- Active infection, heart failure, heart attack within 6 months, unstable angina or unstable arrhythmia.
- Any condition investigator considered may interfere with the results or place the patient at increased risk of treatment complications, or other uncontrollable disease.
- Pregnancy or breast feeding
- Immunodeficiency disorders including human immunodeficiency virus (HIV), or history of organ transplantation, allogeneic stem cell transplantation
- Active hepatitis B virus (HBV) hepatitis (HBV-DNA ≥ 2000 U/mL), hepatitis C virus (HCV) hepatitis, active tuberculosis infection.
- Oncology vaccination history or any vaccination within 4 weeks prior to the start of treatment.(Note: influenza vaccines are mostly inactivated and therefore allowed, intranasal preparations are usually live attenuated vaccines and therefore not allowed)
- Concomitant other immune agents, chemotherapeutic agents, other drugs in clinical studies, and long term cortisol application
Sites / Locations
- Cancer Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College
- National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
iTNT group
TNT group
Arm Description
The intervention of iTNT group is Short-course radiotherapy followed by neoadjuvant chemotherapy and PD-1 inhibitor, which consists of a short-course radiotherapy(SCRT, 5 Gy x 5 alone), then after 14 days of radiotherapy completed, four cycles of PD-1 inhibitor and four cycles of CAPOX or six cycles of mFOLFOX will be performed. The regimen of PD-1 inhibitor and CAPOX treatment includes Sintilimab 200 mg IV, day 1，Oxaliplatin 130 mg/m2 IV day 1，Capecitabine 1000 mg/m2 twice daily PO for 14 days(3 weeks per cycle). The regimen of PD-1 inhibitor and mFOLFOX treatment includes Sintilimab 200 mg IV day 1(3 weeks per cycle), Oxaliplatin 85 mg/m2 IV day 1, Leucovorin 400 mg/m2 IV day 1, 5-FU 400 mg/m2 IV bolus on day 1, then 1200 mg/m2/day x 2 days (total 2400 mg/m2 over 46-48 hours) IV continuous infusion(2 weeks per cycle), then followed by a total mesorectal excision(TME) or Watch & Wait strategy for clinical complete remission voluntary patients.
The intervention of TNT group is Short-course radiotherapy followed by neoadjuvant chemotherapy, which consists of a short-course radiotherapy(SCRT, 5 Gy x 5 alone), then after 14 days of radiotherapy completed, four cycles of CAPOX or six cycles of mFOLFOX will be performed. The regimen of CAPOX treatment includes Oxaliplatin 130 mg/m2 IV day 1，Capecitabine 1000 mg/m2 twice daily PO for 14 days(3 weeks per cycle). The regimen of mFOLFOX treatment includes, Oxaliplatin 85 mg/m2 IV day 1, Leucovorin 400 mg/m2 IV day 1, 5-FU 400 mg/m2 IV bolus on day 1, then 1200 mg/m2/day x 2 days (total 2400 mg/m2 over 46-48 hours) IV continuous infusion(2 weeks per cycle), then followed by a total mesorectal excision(TME) or Watch & Wait strategy for clinical complete remission voluntary patients.
Outcomes
Primary Outcome Measures
complete remission
The rate of pathological complete remission plus clinical complete remission
Disease-free survival rate
Secondary Outcome Measures
Incidence of acute toxicities during radiation, chemotherapy ± immunotherapy
Incidence of surgical complications
Overall survival rate
Locoregional recurrence rate
Distance metastasis rate
Radical resection (R0)
Quality of life (QoL)
Quality of life will be evaluated using EORTC QLQ-C30 (range 0-100). It evaluates the quality of life from 30 aspects, including appetite, mental status, sleep quality, fatigue, etc. The higher scores mean a better quality of life.
Quality of life (QoL)
Quality of life will be evaluated using EORTC QLQ-Cr29 (range 0-100). It evaluates the quality of life from 29 aspects, including defecation function, urine function，pain, sex function, etc. The higher scores mean a better quality of life.
Quality of life (QoL)
Quality of life will be evaluated using Wexner score(range 0-20). It evaluates the defecation function. The lower scores mean a better quality of life.
Full Information
NCT ID
NCT05484024
First Posted
July 21, 2022
Last Updated
July 29, 2022
Sponsor
Chinese Academy of Medical Sciences
1. Study Identification
Unique Protocol Identification Number
NCT05484024
Brief Title
Short-course Radiotherapy Followed by Chemotherapy and PD-1 Inhibitor for Locally Advanced Rectal Cancer
Official Title
Preoperative Short-course Radiotherapy Followed by Chemotherapy With or Without PD-1 Inhibitor for Locally Advanced Rectal Cancer: a Prospective, Multicenter, Randomized Controlled, Phase II/III Study (STELLAR II Study)
Study Type
Interventional
2. Study Status
Record Verification Date
July 2022
Overall Recruitment Status
Not yet recruiting
Study Start Date
August 6, 2022 (Anticipated)
Primary Completion Date
July 31, 2028 (Anticipated)
Study Completion Date
July 31, 2030 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Chinese Academy of Medical Sciences
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
Brief Summary
This phase II/III trial studies how well neoadjuvant short-course radiotherapy and chemotherapy with or without PD-1 inhibitors works in treating patients with locally advanced rectal adenocarcinoma. Neoadjuvant short-course radiation therapy followed by two-drug regimen chemotherapy, such as CAPOX, were shown to be non-inferior to standard long-course chemoradiotherapy in our previous STELLAR study. Immune checkpoint inhibitors (ICIs) using monoclonal antibodies, such as PD-1 or PD-L1 inhibitor, show promising efficiency and reliable security in some limited sample prospective or retrospective studies. When treating patients with locally advanced rectal cancer, giving sequential neoadjuvant short-course radiotherapy and chemotherapy with PD-1 inhibitor may work better.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Rectal Neoplasms Malignant, Radiotherapy
Keywords
rectal cancer, short-course radiotherapy, total neoadjuvant therapy, PD-1 inhibitor
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
588 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
iTNT group
Arm Type
Experimental
Arm Description
The intervention of iTNT group is Short-course radiotherapy followed by neoadjuvant chemotherapy and PD-1 inhibitor, which consists of a short-course radiotherapy(SCRT, 5 Gy x 5 alone), then after 14 days of radiotherapy completed, four cycles of PD-1 inhibitor and four cycles of CAPOX or six cycles of mFOLFOX will be performed. The regimen of PD-1 inhibitor and CAPOX treatment includes Sintilimab 200 mg IV, day 1，Oxaliplatin 130 mg/m2 IV day 1，Capecitabine 1000 mg/m2 twice daily PO for 14 days(3 weeks per cycle). The regimen of PD-1 inhibitor and mFOLFOX treatment includes Sintilimab 200 mg IV day 1(3 weeks per cycle), Oxaliplatin 85 mg/m2 IV day 1, Leucovorin 400 mg/m2 IV day 1, 5-FU 400 mg/m2 IV bolus on day 1, then 1200 mg/m2/day x 2 days (total 2400 mg/m2 over 46-48 hours) IV continuous infusion(2 weeks per cycle), then followed by a total mesorectal excision(TME) or Watch & Wait strategy for clinical complete remission voluntary patients.
Arm Title
TNT group
Arm Type
Active Comparator
Arm Description
The intervention of TNT group is Short-course radiotherapy followed by neoadjuvant chemotherapy, which consists of a short-course radiotherapy(SCRT, 5 Gy x 5 alone), then after 14 days of radiotherapy completed, four cycles of CAPOX or six cycles of mFOLFOX will be performed. The regimen of CAPOX treatment includes Oxaliplatin 130 mg/m2 IV day 1，Capecitabine 1000 mg/m2 twice daily PO for 14 days(3 weeks per cycle). The regimen of mFOLFOX treatment includes, Oxaliplatin 85 mg/m2 IV day 1, Leucovorin 400 mg/m2 IV day 1, 5-FU 400 mg/m2 IV bolus on day 1, then 1200 mg/m2/day x 2 days (total 2400 mg/m2 over 46-48 hours) IV continuous infusion(2 weeks per cycle), then followed by a total mesorectal excision(TME) or Watch & Wait strategy for clinical complete remission voluntary patients.
Intervention Type
Drug
Intervention Name(s)
Sintilimab
Other Intervention Name(s)
Immune checkpoint inhibitor
Intervention Description
PD-1 inhibitor
Intervention Type
Radiation
Intervention Name(s)
Short-course radiotherapy
Other Intervention Name(s)
hypofraction
Intervention Description
Pelvic radiation
Intervention Type
Combination Product
Intervention Name(s)
CAPOX/mFOLFOX
Other Intervention Name(s)
neoadjuvant chemotherapy
Intervention Description
chemotherapy regimen
Primary Outcome Measure Information:
Title
complete remission
Description
The rate of pathological complete remission plus clinical complete remission
Time Frame
one year
Title
Disease-free survival rate
Time Frame
three year
Secondary Outcome Measure Information:
Title
Incidence of acute toxicities during radiation, chemotherapy ± immunotherapy
Time Frame
three months
Title
Incidence of surgical complications
Time Frame
30 days
Title
Overall survival rate
Time Frame
three year
Title
Locoregional recurrence rate
Time Frame
three year
Title
Distance metastasis rate
Time Frame
three year
Title
Radical resection (R0)
Time Frame
one year
Title
Quality of life (QoL)
Description
Quality of life will be evaluated using EORTC QLQ-C30 (range 0-100). It evaluates the quality of life from 30 aspects, including appetite, mental status, sleep quality, fatigue, etc. The higher scores mean a better quality of life.
Time Frame
From date of randomization until the date of death from any cause, assessed up to 10 years
Title
Quality of life (QoL)
Description
Quality of life will be evaluated using EORTC QLQ-Cr29 (range 0-100). It evaluates the quality of life from 29 aspects, including defecation function, urine function，pain, sex function, etc. The higher scores mean a better quality of life.
Time Frame
From date of randomization until the date of death from any cause, assessed up to 10 years
Title
Quality of life (QoL)
Description
Quality of life will be evaluated using Wexner score(range 0-20). It evaluates the defecation function. The lower scores mean a better quality of life.
Time Frame
From date of randomization until the date of death from any cause, assessed up to 10 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Biopsy proven rectal adenocarcinoma;
Distance between tumour and anal verge≤ 10cm;
Locally advanced tumour;(8th edition AJCC/UICC staging :cT3-T4N0/cT2-4N+，M0) Cancer Staging must be based on pelvic MRI or Endoscopic ultrasound;
Eastern Cooperative Oncology Group(ECOG) performance score ≤ 1;
Mentally and physically fit for chemotherapy; Adequate blood counts: White blood cell count ≥3.5 x 109/L Haemoglobin levels ≥100g/L Platelet count ≥100 x 109/L Creatinine levels ≤1.0× upper normal limit（UNL） Urea nitrogen levels ≤1.0× upper normal limit（UNL） Alanine aminotransferase(ALT) ≤1.5× upper normal limit（UNL） Aspartate aminotransferase(AST) ≤1.5× upper normal limit（UNL） Alkaline phosphatase(ALP) ≤1.5× upper normal limit（UNL） Total bilirubin(TBIL)
≤1.5× upper normal limit（UNL）
No excision of tumor, chemotherapy or other anti-tumor treatment after the diagnosis.
No previous pelvic radiation history；
Written informed consent;
Exclusion Criteria:
Previous treatment with anti-PD-1/L1 and anti-CTLA-4 or other immune experimental drugs.
Severe autoimmune disease: active inflammatory bowel disease (including Crohn's disease, ulcerative colitis), rheumatoid arthritis, scleroderma, systemic lupus erythematosus, autoimmune vasculitis (e.g. Wegener's granulomatosis)
Symptomatic interstitial lung disease or active infectious/non-infectious pneumonia.
At risk for bowel perforation: active diverticulitis, intra-abdominal abscess, gastrointestinal (GI) obstruction, abdominal cancer or other known risk factors for bowel perforation.
history of other malignancies, excluding curable non-melanotic skin cancer and cervix carcinoma in situ；
Active infection, heart failure, heart attack within 6 months, unstable angina or unstable arrhythmia.
Any condition investigator considered may interfere with the results or place the patient at increased risk of treatment complications, or other uncontrollable disease.
Pregnancy or breast feeding
Immunodeficiency disorders including human immunodeficiency virus (HIV), or history of organ transplantation, allogeneic stem cell transplantation
Active hepatitis B virus (HBV) hepatitis (HBV-DNA ≥ 2000 U/mL), hepatitis C virus (HCV) hepatitis, active tuberculosis infection.
Oncology vaccination history or any vaccination within 4 weeks prior to the start of treatment.(Note: influenza vaccines are mostly inactivated and therefore allowed, intranasal preparations are usually live attenuated vaccines and therefore not allowed)
Concomitant other immune agents, chemotherapeutic agents, other drugs in clinical studies, and long term cortisol application
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Yuan Tang
Phone
+86-15011304945
Email
tangyuan82@126.com
First Name & Middle Initial & Last Name or Official Title & Degree
Wenjue Zhang
Phone
+86-13620986880
Email
wenjuezhang@163.com
Facility Information:
Facility Name
Cancer Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College
City
Beijing
State/Province
Beijing
Country
China
Facility Name
National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
City
Shenzhen
Country
China
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Short-course Radiotherapy Followed by Chemotherapy and PD-1 Inhibitor for Locally Advanced Rectal Cancer
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