CGA Guided Ultrafractionated RT and Systemic Treatment in Elderly or Frail Patients with Inoperable Localized CRC

Phase 2Not Yet RecruitingNCT06652412

Fudan University124 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Interventions

Ultrafractionated RT and CGA Guided systemic treatment.DRUG

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.

data prospectively collectedOTHER

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.

Ultrafractionated RadiotherapyRADIATION

1Fx every 3 or 4weeks

SintilimabDRUG

200 mg q3w

FluorouracilDRUG

5-Fluorouracil or capecitabine

RaltitrexedDRUG

Raltitrexed

OxaliplatinDRUG

Oxaliplatin

Irinotecan (CPT-11)DRUG

irinotecan

Eligibility

Sex: ALLMin age: 60 Years

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

Complete response (CR) rate

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.

Time frame: 1 month after the surgery or the decision of W&W

Secondary Outcomes

Grade 3-4 adverse effects rate

Rate of chemotherapy, radiotherapy and immunotherapy related adverse events

Time frame: From date of randomization until 3 months after the completion neoadjuvant therapy

1 year anal preservation rate

Time frame: From date of randomization until the date of or date of death from any cause, whichever came first, assessed up to 12 months.

health-related quality of life (HRQOL)

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.

Time frame: baseline, and at 3, 6 and 12 months.

1 year disease free survival rate

Rate of 1 year disease free survival

Time frame: 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.

1 year local recurrence free survival rate

Rate of 1 year local recurrence free survival

Time frame: From date of randomization until the date of first documented pelvic failure, assessed up to 12 months.

1 year Disease-specific survival rate

rate of 1 year Disease-specific survival

Time frame: From date of randomization until the date of death from the specific disease, assessed up to 12 months.

1 year overall survival rate

Rate of 1 year overall survival

Time frame: From date of randomization until the date of death from any cause, assessed up to 12 months.