SBRT Combined With Fruquintinib Plus PD-1/CTLA-4 Antibody for Third-line Treatment in mCRC

SBRT Combined With Fruquintinib Plus PD-1/CTLA-4 Antibody Cadonilimab for Third-line Treatment in Metastatic Colonrectal Cancer.

The study is a phase II clinical study. The purpose of the study is to evaluate the efficacy and safety of SBRT combined with Fruquintinib Plus PD-1/CTLA-4 Antibody for Third-line Treatment in mCRC.

Study Overview

• Status: Not yet recruiting
• Conditions: Metastatic Colorectal Cancer
• Intervention / Treatment: Drug: SBRT, Fruquintinib, Cadonilimab

• Study Type: Interventional
• Enrollment (Anticipated): 44
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Zhenyu Lin; Phone Number: 02785871982; Email: whxhlzy@hust.edu.cn

Study Locations

• China
  • Hubei
    • Wuhan, Hubei, China, 430022
      • Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patients must have biopsy proven unresectable MCRC.
2. Patients must have received first-line and second-line chemotherapy, and approved a progressive disease.
3. Age ≥ 18 years
4. Patients must have measurable disease at baseline.
5. Patients can have up to only 5 discrete active extracranial lesions (≤3 in the liver and ≤3 in the lung) identified by position-emission tomography (PET) scan and also seen on correlative plain film, CT scan, or MRI within 8 weeks prior to the initiation of radiotherapy.
6. Patients who previously received radiotherapy to the primary site will be ineligible if there is CT evidence of disease progression within the past 3 months.
7. Patients must have a Karnofsky Performance Scores (KPS) >60 8. Aspartate aminotransferase, alanine aminotransferase & Alkaline phosphates must be ≤ 2.5 times the upper limit of normal (ULN). Total bilirubin must be within the limit of normal.

9. Patients should have adequate bone marrow function as defined by peripheral granulocyte count of ≥1500/mm3. 10. Patients should have adequate renal function (serum creatinine ≤1.5 times the ULN). 11. Females of childbearing potential should have a negative pregnancy test. 12. Patients who would be receiving radiation for lung lesions who are known or suspected by the treating radiation oncologist to have compromised lung function must have a documented forced expiratory volume in 1 second (FEV1) ≥ 1 litre.

13. Patients must provide verbal and written informed consent to participate in the study.

14. Total bilirubin: within normal institutional limits

Exclusion Criteria:

1. Patients with either untreated brain metastases or brain metastases treated within the past three months are ineligible
2. Patients with serious, uncontrolled, concurrent infection(s).
3. Significant weight loss (>10%) in the prior 3 months.
4. Treatment for other carcinomas within the last five years, except cured non-melanoma skin and treated in-situ cancers.
5. Patients with more than 5 discrete metastatic lesions.
6. Participation in any investigational drug study within 4 weeks preceding the start of study treatment.
7. Unwillingness to participate or inability to comply with the protocol for the duration of the study.
8. Patients who are pregnant. Patients with reproductive capability will need to use adequate contraception during the time of participation in the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SBRT, Fruquintinib, Cadonilimab	Drug: SBRT, Fruquintinib, Cadonilimab; Radiation: Stereotactic body radiationtherapy (SBRT) for metastatic sites (less than 5) Fruquintinib: 5mg, po, everyday; Cadonilimab: 10mg/kg, iv, q3w

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression free survival	Progression free survival	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Toxicities	Acute toxicity was scored according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) v3.0 criteria during and up to 3 months after radiotherapy. Late toxicity was graded using the Radiation Therapy Oncology Group (RTOG)/European Organisation for the Research and Treatment of Cancer (EORTC) criteria.	2 years
Actuarial rate in-field local control	To describe the actuarial rate in-field local control and rate of out-of-field disease progression	2 years

Collaborators and Investigators

• Sponsor: Wuhan Union Hospital, China
• Investigators: Principal Investigator: Tao Zhang, Union Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology

Study record dates

Study Major Dates

• Study Start (Anticipated): February 28, 2023
• Primary Completion (Anticipated): December 31, 2026
• Study Completion (Anticipated): December 31, 2026

Study Registration Dates

• First Submitted: February 18, 2023
• First Submitted That Met QC Criteria: February 18, 2023
• First Posted (Estimate): February 28, 2023

Study Record Updates

• Last Update Posted (Estimate): February 28, 2023
• Last Update Submitted That Met QC Criteria: February 18, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms
• Other Study ID Numbers: MCRC-3

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No