Clinical trial NCT06652412: CGA Guided Ultrafractionated RT and Systemic Treatment in Elderly or Frail Patients with Inoperable Localized CRC
Official title: Comprehensive Geriatric Assessment (CGA) Guided Ultrafractionated Radiotherapy and Systemic Treatment in Elderly or Frail Patients with Inoperable Localized Colorectal Cancer
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Colon Cancer
Rectal Cancer
Lead sponsor: Fudan University
Sponsor class: OTHER
First posted: 2024-10-22
Enrollment: 124
Sex: ALL
Minimum age (years): 60
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Complete response (CR) rate
timeFrame: 1 month after the surgery or the decision of W&W
Secondary outcomes:
measure: Grade 3-4 adverse effects rate
timeFrame: From date of randomization until 3 months after the completion neoadjuvant therapy
measure: 1 year anal preservation rate
timeFrame: From date of randomization until the date of or date of death from any cause, whichever came first, assessed up to 12 months.
measure: health-related quality of life (HRQOL)
timeFrame: baseline, and at 3, 6 and 12 months.
measure: 1 year disease free survival rate
timeFrame: 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.
measure: 1 year local recurrence free survival rate
timeFrame: From date of randomization until the date of first documented pelvic failure, assessed up to 12 months.
measure: 1 year Disease-specific survival rate
timeFrame: From date of randomization until the date of death from the specific disease, assessed up to 12 months.
measure: 1 year overall survival rate
timeFrame: From date of randomization until the date of death from any cause, assessed up to 12 months.
Other outcomes:
Locations:
Study officials:
affiliation: Fudan University
name: Zhen ZHANG Principal Investigator
role: PRINCIPAL_INVESTIGATOR
References: