Abemaciclib Combined With FOLFOX/FOLFIRI Regimen in Patients With Advanced Colorectal Liver Metastases Cancer

Abemaciclib Combined With FOLFOX/FOLFIRI Regimen in Patients With Advanced Colorectal Liver Metastases Cancer Who Failed Standard Two or Three-line Therapy

This is a single-center, single-arm, open-label clinical study, to explore the efficacy and safety of abemaciclib combined with FOLFOX/FOLFIRI regimen in patients with advanced colorectal liver metastases cancer who failed standard two or three-line therapy.

Study Overview

• Status: Enrolling by invitation
• Conditions: Liver Metastases From Colorectal Cancer (mCRC)
• Intervention / Treatment: Drug: Abemaciclib; Drug: Oxaliplatin; Drug: Calcium Folinate; Drug: 5-Fluorouracil; Drug: Irinotecan

Detailed Description

Colorectal Cancer (CRC) is the third most common malignant tumor worldwide, and its mortality rate ranks second globally. Approximately 70% of distant metastases of colorectal cancer occur in the liver, and about 50% of colorectal cancers develop liver metastases (CRLM), which is one of the main factors contributing to the poor prognosis of colorectal cancer. FOLFOX and FOLFIRI regimens are standard therapy for CRLM. Abemaciclib, a FDA approved drug targeting CDK4/6 in breast cancer, also shows anti-tumor activities in other types of solid tumors. In our preclinical experiments, our results also indicated that Abemaciclib conbined with FOLFOX or FOLFIRI regimen showed synergistic anti-tumor activity in CRC.

• Study Type: Interventional
• Enrollment (Estimated): 16
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Shanghai, China, 200032
    • Shanghai Cancer center

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Informed consent has been signed
2. Histologically or cytologically confirmed unresectable advanced colorectal liver metastases cancer
3. Age ≥ 18 years, ≤75 years
4. ECOG PS：0-1
5. Patients who failed standard two or three-line therapy
6. Expected overall survival ≥3 months
7. Patients must have at least one measurable liver metastases (RECIST 1.1)
8. Patients who have previously failed standard treatment, or who cannot tolerate standard treatment
9. Patients must have adequate organ and bone marrow function
10. Women of childbearing age must have a negative pregnancy test within the first day of the study, and contraceptive methods should be taken during the study until 6 months after the last administration

Exclusion Criteria:

1. Patients had other malignant tumors in the past 5 years or at the same time (except for the cured skin basal cell carcinoma and cervical carcinoma in situ);
2. Patients who have previously received CDK inhibitors treatment;
3. Patients with obstruction, bleeding or perforation who require surgical or interventional treatment;
4. Patients who are allergic or suspected to be allergic to the study drug, similar drugs or drug excipients;
5. Patients currently have central nervous system (CNS) metastasis or previous brain metastasis and the symptom control time is less than 2 months;
6. Clinical uncontrolled active infections, including human immunodeficiency virus (HIV) infection, active hepatitis B / C (HBV DNA Positive[1×104 copies/mL or >2000 IU/ml], HCV RNA positive[>1×103 copies/mL]);
7. Clinically significant cardiovascular disease, including but not limited to acute myocardial infarction, severe/unstable angina pectoris or coronary artery bypass grafting within 6 months before enrollment; NYHA classification > 2 Grade; ventricular arrhythmia requiring medical therapy; ECG showing QTc interval > 450 ms (Male) or 470ms (Female);
8. Abnormal coagulation function (INR>2.3 or APTT>1.5×ULN), with a bleeding tendency or currently undergoing thrombolytic or anticoagulant therapy;
9. Hereditary or acquired tendency for bleeding and thrombosis, such as hemophilia, coagulation disorders, thrombocytopenia, hypersplenism;
10. Within 3 months prior to entering the study, clinically bleeding symptoms or bleeding tendency, such as gastrointestinal bleeding without ligation or sclerotherapy injection, hemorrhagic gastric ulcer, positive Fecal Occult Blood Test (++ or above), or suffering from phlebitis;
11. Arterial/venous thrombotic events that occurred within 6 months, such as cerebrovascular accidents (including transient ischemic attack, cerebral hemorrhage, cerebral infarction), deep vein thrombosis and pulmonary embolism;
12. Long-term anticoagulation therapy with warfarin or heparin is required, or long-term antiplatelet therapy (aspirin ≥300 mg/ day or clopidogrel ≥75 mg/ day) is needed;
13. Concurrent severe infection within 2 weeks before the first administration (e.g., requiring intravenous infusion of antibiotics, antifungal or antiviral drugs), or unexplained fever during screening/before the first administration (>38.5°C);
14. A known history of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation;
15. Participating in other clinical trials and received at least one treatment within 3 months before enrollment;
16. A history of abuse or drug use of psychotropic substances;
17. Patients with other serious physical or mental illnesses or abnormal laboratory tests that may increase the risk of participating in the study or interfere with the research results, as well as those deemed unsuitable for participation in this study by the researchers.

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: Abemaciclib+ mFOLFOX/FOLFIRI; Abemaciclib was administered orally at 100-200mg twice daily for each 28-day cycle. mFOLFOX6 and FOLFIRI will be administered every 2-4 weeks.

Drug: Abemaciclib; Abemaciclib was administered orally at 100-200mg twice daily for each 28-day cycle.; Other Names: LY2835219; Drug: Oxaliplatin; 85mg/m², ivdrip, D1; Other Names: L-OHP; Drug: Calcium Folinate; 400mg/m², ivdrip, D1; or calcium levofolinate, 200 mg/m², ivdrip, D1; Other Names: Leucovorin; Drug: 5-Fluorouracil; 400mg/m², iv, D1; and 2400mg/m², civ, 46-48h; Other Names: 5-FU; Fluorouracil; Drug: Irinotecan; 180mg/m², ivdrip, D1; Other Names: CPT-11

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ORR	Objective Response Rate	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
DCR	Disease Control Rate	12 months
TTP	Time To Progression	12 months
ADRs	Adverse Drug Reactions	12 months
PFS	Objective Response Rate	12 months

Collaborators and Investigators

• Sponsor: Fudan University
• Collaborators: Shanghai Cancer Hospital, China

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2026
• Primary Completion (Estimated): April 30, 2027
• Study Completion (Estimated): April 30, 2027

Study Registration Dates

• First Submitted: February 22, 2026
• First Submitted That Met QC Criteria: February 25, 2026
• First Posted (Actual): March 2, 2026

Study Record Updates

• Last Update Posted (Actual): April 27, 2026
• Last Update Submitted That Met QC Criteria: April 22, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: FOLFOX; Abemaciclib; FOLFIRI; Advanced Colorectal Liver Metastases Cancer
• Additional Relevant MeSH Terms: Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Camptothecin; Alkaloids; Enzymes and Coenzymes; Coordination Complexes; Pyrimidines; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Uracil; Pyrimidinones; Coenzymes; Oxaliplatin; Irinotecan; Fluorouracil; Leucovorin; abemaciclib
• Other Study ID Numbers: GWK-2026-002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

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.: Yes