Fruquintinib and Pirfenidone in Combination With Anti-PD-1 Antibody in Advanced or Metastatic pMMR/MSS Colorectal Carcinoma

NCT ID: NCT06484153

Last Updated: 2024-07-03

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 25 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-07-22
• Study Completion Date: 2026-12-30

Brief Summary

The purpose of this study is to evaluate the efficacy and safety of fruquintinib and pirfenidone in combination with anti-PD-1 antibody in patients with standard treatment failure of advanced or metastatic pMMR/MSS colorectal adenocarcinoma.

Detailed Description

In this study, we explored the potential effectiveness of fruquintinib and pirfenidone in combination with anti-PD-1 antibody, in MSS/pMMR unresectable locally advanced or metastatic colorectal cancer patients who failed standard chemotherapy and testified this new combination in preclinical models. 25 patients were included.

Conditions

To Evaluate the Efficacy of Fruquintinib and Pirfenidone in Combination With Anti-PD-1 Antibody in Colorectal Carcinoma; To Evaluate Whether Pirfenidone Can Reshape the Tumor Microenvironment in Colorectal Cancer; Combination of Fruquintinib and Anti-PD-1 Antibody Was Reported to Improve Patient Prognosis in Colorectal Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment

Pembrolizumab intravenous (IV) 200mg flat dose day 1 then every 3 weeks. Fruquintinib orally (PO) 3mg po qd.

Pirfenidone (Esbriet) orally (PO) with food according to this schedule:

two dose groups: 200mg, TID, po;500mg, TID ,po. Using "3-3" design, the observation period of DLT was 28 days.

Group Type: EXPERIMENTAL

Pirfenidone

Intervention Type: DRUG

Two doses of pirfenidone (200 mg,tid,po;500 mg,tid,po) were set up. Using the 3+3 design, the DLT observation period is 28 days.

Fruquintinib

Intervention Type: DRUG

3mg, orally, qd

Pembrolizumab

Intervention Type: DRUG

200mg iv every 3 weeks

Interventions

Pirfenidone

Two doses of pirfenidone (200 mg,tid,po;500 mg,tid,po) were set up. Using the 3+3 design, the DLT observation period is 28 days.

Intervention Type: DRUG

Fruquintinib

3mg, orally, qd

Intervention Type: DRUG

Pembrolizumab

200mg iv every 3 weeks

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Histologically confirmed diagnosis of unresectable locally advanced, recurrent or metastatic colorectal adenocarcinoma.

2. Tumor tissues were identified as mismatch repair-proficient (pMMR) by immunohistochemistry (IHC) method or microsatellite stability (MSS) by polymerase chain reaction (PCR).

3. Subjects must have failed at least two lines of prior treatment.

4. Subjects must have one measurable lesion according to RECIST v1.1 at least.

5. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1. 6. 18-75 years old.

7. Life expectancy of at least 12 weeks. 8. Adequate bone marrow, liver, renal and coagulation function as assessed by the laboratory required by protocol

Exclusion Criteria

1. Previously received anti-programmed death-1 (PD-1) or its ligand (PD-L1) antibody or Pirfenidone.

2. Received last dose of anti-tumor therapy (chemotherapy, targeted therapy, tumor immunotherapy or arterial embolization) within 3 weeks of the first dose of study medication.

3. Received radiotherapy with 4 weeks of the first dose of study medication.

4. Underwent major operation within 4 weeks of the first dose of study medication or open wound, ulcer or fracture.

5. Known symptomatic central nervous system (CNS) metastasis and/or carcinomatous meningitis. Subjects received prior treatment and have stable disease more than 4 weeks from first dose of study medication are permitted to enroll.

6. Active, known or suspected autoimmune disease or has a history of the disease within the last 2 years.

7. Interstitial lung disease requiring corticosteroids.

8. Active or poorly controlled serious infections.

9. Significant malnutrition.

10. Symptomatic congestive heart failure (NYHA Class II-IV) or symptomatic or poorly controlled arrhythmia.

11. Uncontrolled hypertension (systolic blood pressure ≥ 150 mmHg or diastolic blood pressure ≥ 100 mmHg) despite standard treatment.

12. Within 6 months prior to the enrollment, history of gastrointestinal perforation and/or fistula, gastrointestinal ulcer, bowel obstruction, extensive bowel resection, Crohn's disease, or ulcerative colitis, intra-abdominal abscesses, or long-term chronic diarrhea.

13. History or evidence of inherited bleeding diathesis or coagulopathy or thrombus

14. Any life-threatening bleeding within 3 months prior to the enrollment.

15. High risk of bleeding.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

OTHER

Sponsor Role: lead

Responsible Party

Tao Zhang

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Central Contacts

Tao Zhang, MD

Role: CONTACT

whxhlzy@hust.edu.cn

86+02785871982

Other Identifiers

union-P

Identifier Type: -

Identifier Source: org_study_id