Clinical trial NCT06665087: CGA Guided Ultrafractionated RT and First-line Systemic Treatment in Elderly or Frail Patients with MCRC
Official title: Comprehensive Geriatric Assessment (CGA) Guided Ultrafractionated Radiotherapy and First-line Systemic Treatment in Elderly or Frail Patients with Metastatic 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: 2024-10-30
Enrollment: 110
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(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.

Eligibility criteria: 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.

Primary outcomes:
measure: Progression Free Survival
timeFrame: 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 outcomes:
measure: Grade 3-4 adverse effects rate
timeFrame: From the start of treatment until 3 months after the completion of therapy.
measure: the Overall Response Rate (ORR)
timeFrame: up to 1 year since the start of treatment.
measure: health-related quality of life (HRQOL)
timeFrame: baseline, and at 3, 6 and 12 months.
measure: health-related quality of life (HRQOL)
timeFrame: baseline, and at 3, 6 and 12 months.
measure: 1-year Disease-specific survival (DSS) rate
timeFrame: From the start of treatment until the date of death from the specific disease, assessed up to 12 months.
measure: 1-year overall survival (OS) rate
timeFrame: From the start of treatment 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: