Combination of Fruquintinib and Anti-PD-1 Antibody Was Reported to Improve Patient Prognosis in Colorectal Cancer, 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
Conditions
Keywords
Pirfenidone,tumor microenvironment, PD-1 antibody
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.
Interventions
DRUGPirfenidone
Pirfenidone: Day 1 to Day 14: 200 mg, oral administration (po), three times daily (tid); Day 15 to Day 29: 400 mg, po, tid; Day 30 until progressive disease: 600 mg, po, tid.
DRUGFruquintinib
3mg, orally, qd
DRUGPembrolizumab
200mg iv every 3 weeks
Sponsors
Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival (PFS) | 2 year | The time from enrollment until tumor progression or death from any cause, whichever occurred first |
| Occurrence of Grade 4 toxicity | Cycle 1 day 1 to Cycle 3 day 1 (Each cycle is 21 days) | CTCAE v5.0 |
| Occurrence of Grade 3 toxicity | Cycle 1 day 1 to Cycle 3 day 1 (Each cycle is 21 days | CTCAE v5.0 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | 2 year | The time calculated from enrollment until death from any cause, with living patients censored at the last known survival date |
| Objective response rate (ORR) | 2 year | The proportion of patients with a PR or CR |
| Disease control rate (DCR) | 2 year | The proportion of patients with a PR, CR, or SD |
| Duration of response (DoR) | 2 year | For patients who achieved a complete response (CR) or partial response (PR), the time from the first tumor assessment demonstrating response until disease progression or death, whichever occurred first |
Countries
China
Contacts
CONTACTTao Zhang, MD
Outcome results
None listed