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

NCT06484153 | Not Yet Recruiting Phase 1

• 1 other identifier: union-P
• Study Type: interventional
• Target: 25
• Locations: 0 countries
• Sites: N/A

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.

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

Outcome Measures

Primary Outcomes (3)

• Progression Free Survival (PFS)

  The time from enrollment until tumor progression or death from any cause, whichever occurred first

  2 year

• Occurrence of Grade 4 toxicity

  CTCAE v5.0

  Cycle 1 day 1 to Cycle 3 day 1 (Each cycle is 21 days)

• Occurrence of Grade 3 toxicity

  CTCAE v5.0

  Cycle 1 day 1 to Cycle 3 day 1 (Each cycle is 21 days

Secondary Outcomes (4)

• Objective response rate (ORR)

  2 year

• Overall Survival (OS)

  2 year

• Disease control rate (DCR)

  2 year

• Duration of response (DoR)

  2 year

Study Arms (1)

Treatment

EXPERIMENTAL

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.

Drug: Pirfenidone; Drug: Fruquintinib; Drug: Pembrolizumab

Interventions

Pirfenidone 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.

Treatment

Fruquintinib DRUG

3mg, orally, qd

Treatment

Pembrolizumab DRUG

200mg iv every 3 weeks

Treatment

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed diagnosis of unresectable locally advanced, recurrent or metastatic colorectal adenocarcinoma.
• Tumor tissues were identified as mismatch repair-proficient (pMMR) by immunohistochemistry (IHC) method or microsatellite stability (MSS) by polymerase chain reaction (PCR).
• Subjects must have failed at least two lines of prior treatment.
• Subjects must have one measurable lesion according to RECIST v1.1 at least.
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1. 6. 18-75 years old.
• \. Life expectancy of at least 12 weeks. 8. Adequate bone marrow, liver, renal and coagulation function as assessed by the laboratory required by protocol

You may not qualify if:

• Previously received anti-programmed death-1 (PD-1) or its ligand (PD-L1) antibody or Pirfenidone.
• 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.
• Received radiotherapy with 4 weeks of the first dose of study medication.
• Underwent major operation within 4 weeks of the first dose of study medication or open wound, ulcer or fracture.
• 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.
• Active, known or suspected autoimmune disease or has a history of the disease within the last 2 years.
• Interstitial lung disease requiring corticosteroids.
• Active or poorly controlled serious infections.
• Significant malnutrition.
• Symptomatic congestive heart failure (NYHA Class II-IV) or symptomatic or poorly controlled arrhythmia.
• Uncontrolled hypertension (systolic blood pressure ≥ 150 mmHg or diastolic blood pressure ≥ 100 mmHg) despite standard treatment.
• 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.
• History or evidence of inherited bleeding diathesis or coagulopathy or thrombus
• Any life-threatening bleeding within 3 months prior to the enrollment.
• High risk of bleeding.

Sponsors & Collaborators

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

MeSH Terms

Interventions

pirfenidone; HMPL-013; pembrolizumab

Central Study Contacts

Tao Zhang, MD

CONTACT

86+02785871982; whxhlzy@hust.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: May 24, 2024
• First Posted: July 3, 2024
• Study Start: July 22, 2024
• Primary Completion (Estimated): July 22, 2026
• Study Completion (Estimated): December 30, 2026
• Last Updated: July 3, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: 5 years