Clinical trial NCT06484153: Fruquintinib and Pirfenidone in Combination With Anti-PD-1 Antibody in Advanced or Metastatic pMMR/MSS Colorectal Carcinoma
Official title: A Randomized Phase 1b/2 Clinical Trial Evaluating Fruquintinib and Pirfenidone in Combination With Anti-PD-1 Antibody in Patients With Standard Treatment Failure of Advanced or Metastatic pMMR/MSS Colorectal Carcinoma
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE1
PHASE2
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
Keywords: Pirfenidone,tumor microenvironment, PD-1 antibody
Lead sponsor: Wuhan Union Hospital, China
Sponsor class: OTHER
First posted: 2024-07-03
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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\&#39;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.

Primary outcomes:
measure: Progression Free Survival (PFS)
timeFrame: 2 year
measure: Occurrence of Grade 4 toxicity
timeFrame: Cycle 1 day 1 to Cycle 3 day 1 (Each cycle is 21 days)
measure: Occurrence of Grade 3 toxicity
timeFrame: Cycle 1 day 1 to Cycle 3 day 1 (Each cycle is 21 days
Secondary outcomes:
measure: Objective response rate (ORR)
timeFrame: 2 year
measure: Overall Survival (OS)
timeFrame: 2 year
measure: Disease control rate (DCR)
timeFrame: 2 year
measure: Duration of response (DoR)
timeFrame: 2 year
Other outcomes:
Locations:
Study officials:
References: