Colon Cancer, Rectal Cancer
Conditions
Brief summary
This is a prospective, multicentre, cohort study. For cohort 1, experimental cohort, older or Frail patients with inoperable localized colorectal cancer will receive Ultrafractionated Radiotherapy (RT) and Comprehensive Geriatric Assessment (CGA) Guided systemic treatment. All patients will receive Ultrafractionated RT and PD-1 antibody. Furthermore, CGA will assess all patients and classify them into Frail, Vulnerabe, or Fit. Frail patients will receive Best Supportive Care (BSC); Vulnerabe patients will receive Fluorouracil/Raltitrexed and BSC; Fit patients will receive Fluorouracil/Raltitrexed, Oxaliplatin/Irinotecan, and BSC. For cohort 2, external control from real word, data of patients with the same baseline characteristics from the same period and the same institute will be prospectively collected. The primary endpoint is complete response (CR, pathological complete response \[pCR\] plus clinical complete response \[cCR\]) rate. The secondary endpoints include the grade 3-4 acute adverse effects rate, anal preservation rate, survival etc.
Detailed description
This is a prospective, multicentre, cohort study. For cohort 1, experimental cohort, older or Frail patients with inoperable localized colorectal cancer will receive Ultrafractionated Radiotherapy (RT) and Comprehensive Geriatric Assessment (CGA) Guided systemic treatment. All patients will receive Ultrafractionated RT and PD-1 antibody. Furthermore, CGA will assess all patients and classify them into Frail, Vulnerabe, or Fit. Frail patients will receive Best Supportive Care (BSC); Vulnerabe patients will receive Fluorouracil/Raltitrexed and BSC; Fit patients will receive Fluorouracil/Raltitrexed, Oxaliplatin/Irinotecan, and BSC. For cohort 2, external control from real word, data of patients with the same baseline characteristics from the same period and the same institute will be prospectively collected. The primary endpoint is complete response (CR, pathological complete response \[pCR\] plus clinical complete response \[cCR\]) rate. The secondary endpoints include the grade 3-4 acute adverse effects rate, anal preservation rate, 1-year DFS rate, 1-year DSS rate, 1-year OS rate etc.
Interventions
in cohort 1, all patients will receive Ultrafractionated RT (1Fx every 3 or 4weeks) and Sintilimab (q3w). Furthermore, CGA will assess all patients and classify them into Frail, Vulnerabe, or Fit. Frail patients will receive Best Supportive Care (BSC); Vulnerabe patients will receive Fluorouracil/Raltitrexed and BSC; Fit patients will receive Fluorouracil/Raltitrexed, Oxaliplatin/Irinotecan, and BSC.
OTHERdata prospectively collected
in cohort 2, external control from real word, data of patients with the same baseline characteristics from the same period and the same institute will be prospectively collected.
RADIATIONUltrafractionated Radiotherapy
1Fx every 3 or 4weeks
DRUGSintilimab
200 mg q3w
DRUGFluorouracil
5-Fluorouracil or capecitabine
DRUGRaltitrexed
Raltitrexed
DRUGOxaliplatin
Oxaliplatin
irinotecan
Sponsors
Fudan University
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
60 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. ≥70y, or, ≥60 and \<70y but ECOG≥2; 2. male or female; 3. Pathologically confirmed Colorectal adenocarcinoma; 4. any distance from anal verge; 5. Clinical stage ≥T2 and/or N+, without distance metastases; 6. refuse radical operation, physiologically or technically inoperable; 7. No previous radiotherapy in the same field； 8. No chemotherapy prior to enrollment; 9. No immunotherapy prior to enrollment; 10. With good compliance during the study 11. Signed written informed consent
Exclusion criteria
1. Known history of other malignancies within 3 years，except cured skin cancer, cervical cancer in situ or thyroid carcinoma. 2. Individuals with a history of uncontrolled epilepsy, central nervous system disease, or psychiatric disorders that, in the judgment of the investigator, are of such clinical severity that they may prevent the signing of an informed consent form or affect the patient's adherence to oral medications 3. Individuals with clinically serious (i.e., active) heart disease, such as symptomatic coronary artery disease, New York Heart Association (NYHA) class II or worse congestive heart failure or severe arrhythmia requiring pharmacologic intervention, or history of myocardial infarction within the last 12 months 4. Individuals with a history of organ transplantation requiring immunosuppressive therapy and long-term hormone therapy 5. Individuals with autoimmune diseases 6. Individuals with severe uncontrolled recurrent infections, or other severe uncontrolled concomitant diseases 7. Baseline hematology and biochemistry did not meet the following criteria: Hb≥90g/L; NEU ≥1.5×109/L; PLT ≥100×109/L; ALT, AST ≤2.5 times the upper limit of normal; ALP ≤2.5 times the upper limit of normal; TB \<1.5 times the upper limit of normal; Cr \<1 time the upper limit of normal; Alb ≥30g/L 8. Individuals allergic to any drug component of the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Complete response (CR) rate | 1 month after the surgery or the decision of W&W | Rate of complete response (CR), including the rate of pathologic complete response (pCR) after surgery and the rate of clinical complete response (cCR) with Watch & Wait (W&W) strategy. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 1 year anal preservation rate | From date of randomization until the date of or date of death from any cause, whichever came first, assessed up to 12 months. | 1 year anal preservation rate |
| health-related quality of life (HRQOL) | baseline, and at 3, 6 and 12 months. | HRQOL assessed with validated European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ) ColoRectal cancer (CR) with 29 items (C29) and with 30 items (C30). Multiple measurements and scores will be aggregated to arrive at one reported value. Scores at different time points after randomization will be compared to baseline scores. |
| 1 year disease free survival rate | From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 12 months. | Rate of 1 year disease free survival |
| Grade 3-4 adverse effects rate | From date of randomization until 3 months after the completion neoadjuvant therapy | Rate of chemotherapy, radiotherapy and immunotherapy related adverse events |
| 1 year Disease-specific survival rate | From date of randomization until the date of death from the specific disease, assessed up to 12 months. | rate of 1 year Disease-specific survival |
| 1 year overall survival rate | From date of randomization until the date of death from any cause, assessed up to 12 months. | Rate of 1 year overall survival |
| 1 year local recurrence free survival rate | From date of randomization until the date of first documented pelvic failure, assessed up to 12 months. | Rate of 1 year local recurrence free survival |
Contacts
Primary ContactZhen ZHANG Principal Investigator
Backup ContactYan WANG sub-Investigator
Outcome results
None listed