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

Fudan University

Status and phase: Not yet enrolling; Phase 2

Conditions: Colon Cancer; Rectal Cancer

Treatments: Drug: Irinotecan (CPT-11); Drug: Raltitrexed; Drug: Oxaliplatin; Drug: Fluorouracil; Other: data prospectively collected; Radiation: Ultrafractionated Radiotherapy; Drug: Sintilimab; Drug: Ultrafractionated RT and CGA Guided systemic treatment.

Study type: Interventional

Funder types: Other

Identifiers

NCT06652412

FDRT-2024-137-3690

Details and patient eligibility

About

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.

Full 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.

Enrollment: 124 estimated patients

Sex: All

Ages: 60+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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124 participants in 2 patient groups

CGA cohort

Experimental group

Description:

in cohort 1, all patients will receive Ultrafractionated RT, PD-1 antibody, and Comprehensive Geriatric Assessment (CGA) Guided systemic treatment. 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 single agent chemotherapy and BSC; Fit patients will receive doublet chemotherapy and BSC.

Treatment:

Drug: Ultrafractionated RT and CGA Guided systemic treatment.

Drug: Sintilimab

Radiation: Ultrafractionated Radiotherapy

Drug: Fluorouracil

Drug: Oxaliplatin

Drug: Irinotecan (CPT-11)

Drug: Raltitrexed

external control cohort

Other group

Description:

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.

Treatment:

Other: data prospectively collected