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

Comprehensive Geriatric Assessment (CGA) Guided Ultrafractionated Radiotherapy and First-line Systemic Treatment in Elderly or Frail Patients with Metastatic Colorectal Cancer

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Rectal Cancer; Colon Cancer
• Intervention / Treatment: Radiation: Ultrafractionated Radiotherapy; Drug: Ultrafractionated RT and CGA Guided systemic treatment.; Drug: PD-1 antibody; Drug: Chemotherapy (Fluorouracil); Drug: Chemotherapy (Raltitrexed); Drug: Chemotherapy (Oxaliplatin); Drug: Chemotherapy (CPT-11); Drug: Targeted Therapy (anti-VEGF); Drug: Targeted Therapy (anti-EGFR)

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 Type: Interventional
• Enrollment (Estimated): 110
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Zhen ZHANG Principal Investigator; Phone Number: 18801735029; Email: zhen_zhang@fudan.edu.cn
• Study Contact Backup: Name: Yan WANG sub-Investigator; Phone Number: 18121298388; Email: 11111230025@fudan.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: 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.	Drug: Chemotherapy (Fluorouracil); 5-Fluorouracil or capecitabine; Drug: Chemotherapy (Raltitrexed); Raltitrexed; Drug: Chemotherapy (Oxaliplatin); Oxaliplatin; Drug: Chemotherapy (CPT-11); Irinotecan; Drug: Targeted Therapy (anti-VEGF); anti-VEGF antibody; Drug: Targeted Therapy (anti-EGFR); anti-EGFR antibody
Experimental: CGA cohort; 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.	Radiation: Ultrafractionated Radiotherapy; 1Fx every 3 or 4weeks; Drug: Ultrafractionated RT and CGA Guided systemic treatment.; 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, with/without targeted therapy, and BSC; Fit patients will receive Fluorouracil/Raltitrexed, Oxaliplatin/Irinotecan, with/without targeted therapy, and BSC.; Drug: PD-1 antibody; Sintilimab; Drug: Chemotherapy (Fluorouracil); 5-Fluorouracil or capecitabine; Drug: Chemotherapy (Raltitrexed); Raltitrexed; Drug: Chemotherapy (Oxaliplatin); Oxaliplatin; Drug: Chemotherapy (CPT-11); Irinotecan; Drug: Targeted Therapy (anti-VEGF); anti-VEGF antibody; Drug: Targeted Therapy (anti-EGFR); anti-EGFR antibody

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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

Outcome Measure	Measure Description	Time Frame
Grade 3-4 adverse effects rate	Rate of chemotherapy, radiotherapy, targeted therapy, and immunotherapy related adverse events.	From the start of treatment until 3 months after the completion of therapy.
the Overall Response Rate (ORR)	the percentage of patients with a best overall response of complete response or partial response.	up to 1 year since the start of treatment.
health-related quality of life (HRQOL)	EORTC QLQ C30 [The European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ) Core with 30 items] will be filled by all patients. Scores at different time points after treatment will be compared to baseline scores.	baseline, and at 3, 6 and 12 months.
health-related quality of life (HRQOL)	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.	baseline, and at 3, 6 and 12 months.
1-year Disease-specific survival (DSS) rate	rate of 1 year Disease-specific survival	From the start of treatment until the date of death from the specific disease, assessed up to 12 months.
1-year overall survival (OS) rate	rate of 1 year overall survival	From the start of treatment until the date of death from any cause, assessed up to 12 months.

Collaborators and Investigators

• Sponsor: Fudan University
• Investigators: Principal Investigator: Zhen ZHANG Principal Investigator, Fudan University

Study record dates

Study Major Dates

• Study Start (Estimated): November 1, 2024
• Primary Completion (Estimated): November 1, 2027
• Study Completion (Estimated): November 1, 2028

Study Registration Dates

• First Submitted: October 24, 2024
• First Submitted That Met QC Criteria: October 28, 2024
• First Posted (Actual): October 30, 2024

Study Record Updates

• Last Update Posted (Actual): October 30, 2024
• Last Update Submitted That Met QC Criteria: October 28, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Intestinal Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colorectal Neoplasms; Intestinal Neoplasms; Rectal Diseases; Colonic Diseases; Rectal Neoplasms; Colonic Neoplasms; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Folic Acid Antagonists; Oxaliplatin; Fluorouracil; Raltitrexed; Antibodies
• Other Study ID Numbers: FDRT-2024-157-3710

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No