CGA Guided Ultrafractionated RT and First-line Systemic Treatment in Elderly or Frail Patients with MCRC

Phase 2

Not yet recruiting

• Conditions: Colon Cancer; Rectal Cancer
• Interventions: Drug: Ultrafractionated RT and CGA Guided systemic treatment.; Radiation: Ultrafractionated Radiotherapy; Drug: PD-1 antibody; Drug: Chemotherapy (CPT-11); Drug: Chemotherapy (Fluorouracil); Drug: Targeted Therapy (anti-VEGF); Drug: Chemotherapy (Raltitrexed); Drug: Targeted Therapy (anti-EGFR); Drug: Chemotherapy (Oxaliplatin)

• Registration Number: NCT06665087
• Lead Sponsor: Fudan University

Brief Summary

This is a prospective, multicentre, cohort study. For cohort 1(CGA cohort), experimental cohort, older or Frail patients with metastatic 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 single agent chemotherapy, with/without targeted therapy, and BSC; Fit patients will receive doublet chemotherapy, with/without targeted therapy, and BSC.

For cohort 2 (external control cohort), 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 Progression Free Survival (PFS). The secondary endpoints include the grade 3-4 acute adverse effects (AE) rate, quality of life (QoL), the Overall Response Rate (ORR), 1-year Disease-specific survival (DSS) rate, 1-year overall survival (OS) rate etc.

Detailed Description

This is a prospective, multicentre, cohort study. For cohort 1(CGA cohort), experimental cohort, older or Frail patients with metastatic 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, with/without targeted therapy, and BSC; Fit patients will receive Fluorouracil/Raltitrexed, Oxaliplatin/Irinotecan, with/without targeted therapy, and BSC.

For cohort 2 (external control cohort), 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 Progression Free Survival (PFS). The secondary endpoints include the grade 3-4 acute adverse effects (AE) rate, quality of life (QoL), the Overall Response Rate (ORR), 1-year Disease-specific survival (DSS) rate, 1-year overall survival (OS) rate etc.

Study Timeline

• Status Verified: 2024-10
• Study First Submitted: 2024-10-24
• Study First Submitted QC: 2024-10-28
• Last Update Submitted: 2024-10-28
• Study First Posted: 2024-10-30
• Last Update Posted: 2024-10-30
• Study Start: 2024-11
• Primary Completion: 2027-11
• Study Completion: 2028-11

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 110

Inclusion Criteria

1. ≥70y, or, ≥60 and <70y but ECOG≥2;
2. male or female;
3. metastatic colorectal cancer;
4. at least one measurable leasion;
5. the primary lesion could be 1)previously resected, or 2) not resected or recurred, and not been previously irradiated;
6. no more than 10 lesions, and all the lesions could be safely irradiated.
7. life expectancy is more than 3 months;
8. no previous standard first-line anti-cancer treatment(including 5-FU/ Capecitabine/Raltitrexed, oxaliplatin, or irinotecan), or more than 6 months after perioperative chemotherapy;
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, thyroid carcinoma, or clinical controlled prostate cancer;
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≥80g/L; NEU ≥1.5×109/L; PLT ≥100×109/L（PLT ≥80×109/L if there were liver metastasis）; 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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
external control cohort	Chemotherapy (CPT-11)	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.
external control cohort	Targeted Therapy (anti-VEGF)	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.
external control cohort	Targeted Therapy (anti-EGFR)	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.
CGA cohort	Ultrafractionated RT and CGA Guided systemic treatment.	all patients 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, with/without targeted therapy, and BSC; Fit patients will receive Fluorouracil/Raltitrexed, Oxaliplatin/Irinotecan, with/without targeted therapy, and BSC.
CGA cohort	Ultrafractionated Radiotherapy	all patients 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, with/without targeted therapy, and BSC; Fit patients will receive Fluorouracil/Raltitrexed, Oxaliplatin/Irinotecan, with/without targeted therapy, and BSC.
CGA cohort	PD-1 antibody	all patients 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, with/without targeted therapy, and BSC; Fit patients will receive Fluorouracil/Raltitrexed, Oxaliplatin/Irinotecan, with/without targeted therapy, and BSC.
CGA cohort	Chemotherapy (Fluorouracil)	all patients 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, with/without targeted therapy, and BSC; Fit patients will receive Fluorouracil/Raltitrexed, Oxaliplatin/Irinotecan, with/without targeted therapy, and BSC.
CGA cohort	Chemotherapy (Raltitrexed)	all patients 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, with/without targeted therapy, and BSC; Fit patients will receive Fluorouracil/Raltitrexed, Oxaliplatin/Irinotecan, with/without targeted therapy, and BSC.
CGA cohort	Chemotherapy (Oxaliplatin)	all patients 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, with/without targeted therapy, and BSC; Fit patients will receive Fluorouracil/Raltitrexed, Oxaliplatin/Irinotecan, with/without targeted therapy, and BSC.
CGA cohort	Chemotherapy (CPT-11)	all patients 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, with/without targeted therapy, and BSC; Fit patients will receive Fluorouracil/Raltitrexed, Oxaliplatin/Irinotecan, with/without targeted therapy, and BSC.
CGA cohort	Targeted Therapy (anti-VEGF)	all patients 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, with/without targeted therapy, and BSC; Fit patients will receive Fluorouracil/Raltitrexed, Oxaliplatin/Irinotecan, with/without targeted therapy, and BSC.
CGA cohort	Targeted Therapy (anti-EGFR)	all patients 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, with/without targeted therapy, and BSC; Fit patients will receive Fluorouracil/Raltitrexed, Oxaliplatin/Irinotecan, with/without targeted therapy, and BSC.
external control cohort	Chemotherapy (Fluorouracil)	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.
external control cohort	Chemotherapy (Raltitrexed)	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.
external control cohort	Chemotherapy (Oxaliplatin)	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.

Primary Outcome Measures

Name	Time	Method
Progression Free Survival	From the start of treatment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months

Secondary Outcome Measures

Name	Time	Method
Grade 3-4 adverse effects rate	From the start of treatment until 3 months after the completion of therapy.	Rate of chemotherapy, radiotherapy, targeted therapy, and immunotherapy related adverse events.
the Overall Response Rate (ORR)	up to 1 year since the start of treatment.	the percentage of patients with a best overall response of complete response or partial response.
health-related quality of life (HRQOL)	baseline, and at 3, 6 and 12 months.	EORTC QLQ CR29 \[The European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ) ColoRectal cancer (CR) with 29 items\] will be filled out by all patients. Scores at different time points after treatment will be compared to baseline scores.
1-year Disease-specific survival (DSS) rate	From the start of treatment 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 (OS) rate	From the start of treatment until the date of death from any cause, assessed up to 12 months.	rate of 1 year overall survival