A Phase II Study of Pirfenidone Plus PD-1 Inhibitor With or Without Hypofractionated Radiotherapy for Refractory pMMR/MSS Colorectal Cancer

NCT07644286 | Recruiting Phase 2

• 1 other identifier: PFD20251116
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

Brief Summary

This study aims to evaluate the safety, tolerability, and efficacy of pirfenidone and PD-1 monoclonal antibody combined with or without hypofractionated radiotherapy in the treatment of advanced refractory pMMR/MSS colorectal cancer patients.

Conditions

Colorectal Cancer (CRC)

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival（PFS）

  Progression-free survival (PFS) is defined as the time from the initiation of study treatment to the first occurrence of disease progression or death from any cause, whichever comes first.

  an expected average of 6 months

Secondary Outcomes (3)

• Overall Survival

  an expected average of 5 years

• Objective Response Rate

  an expected average of 2 years

• dverse events (AEs) were graded according to the NCI CTCAE version 5·0

  an expected average of 1.5 years

Study Arms (2)

Pirfenidone in combination with a PD-1 inhibitor and hypofractionated radiotherapy

EXPERIMENTAL

Patients will receive a PD-1 inhibitor (200 mg, intravenously, every 3 weeks) in combination with oral pirfenidone. The dose of pirfenidone will be up-titrated as follows: from days 1 to 14 at 200 mg three times daily (TID); from days 15 to 29 at 400 mg TID; and from day 30 onwards at a maintenance dose of 600 mg TID. Pirfenidone will be continued until disease progression or unacceptable toxicity. Additionally, patients will undergo hypofractionated radiotherapy to the metastatic site(s) with a dose of 5 to 8 Gy per fraction for a total of 5 consecutive fractions.

Drug: Pirfenidone in combination with a PD-1 inhibitor; Radiation: hypofractionated radiotherapy

Pirfenidone in combination with a PD-1 inhibitor

EXPERIMENTAL

Patients will receive a PD-1 inhibitor (200 mg, intravenously, every 3 weeks) in combination with oral pirfenidone. The dose of pirfenidone will be up-titrated as follows: from days 1 to 14 at 200 mg three times daily (TID); from days 15 to 29 at 400 mg TID; and from day 30 onwards at a maintenance dose of 600 mg TID. Pirfenidone will be continued until disease progression or unacceptable toxicity.

Drug: Pirfenidone in combination with a PD-1 inhibitor

Interventions

hypofractionated radiotherapy RADIATION

hypofractionated radiotherapy

Pirfenidone in combination with a PD-1 inhibitor and hypofractionated radiotherapy

Pirfenidone in combination with a PD-1 inhibitor DRUG

The PD-1 inhibitor will be administered intravenously at 200 mg every 3 weeks. Pirfenidone dosing will follow an escalating regimen: 200 mg orally three times daily, 400 mg orally three times daily, and 600 mg orally three times daily.

Pirfenidone in combination with a PD-1 inhibitor; Pirfenidone in combination with a PD-1 inhibitor and hypofractionated radiotherapy

Eligibility Criteria

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

You may qualify if:

• Written informed consent must be provided, and the patient must be able to comply with the visit schedule and procedures outlined in the protocol.
• Age ≥ 18 years and ≤ 75 years, regardless of gender.
• Histologically or cytologically confirmed, unresectable locally advanced or metastatic pMMR/MSS colorectal cancer.
• Patients must have progressed on standard therapy, be unsuitable for standard therapy due to intolerable toxicity, have no available standard therapy, or have refused standard therapy.
• Baseline\* hematology tests (within 7 days prior to the first dose of study drug) must meet the following criteria:Hemoglobin ≥ 90 g/L (without transfusion or erythropoietin support within 7 days prior to blood sampling).
• Absolute Neutrophil Count (ANC) ≥ 1.5 × 10⁹/L (without granulocyte colony-stimulating factor support within 7 days prior to blood sampling).Platelet count ≥ 100 × 10⁹/L (without transfusion support within 7 days prior to blood sampling).Eosinophil count ≤ 1.5 × ULN.
• Throughout the protocol, "baseline" is defined as the last available observation prior to the first dose of the study drug. Patients must not have received any blood products or hematopoietic growth factor support within 7 days prior to the blood sample collection.
• Serum creatinine ≤ 1.5 × ULN or Calculated Creatinine Clearance (CrCl) ≥ 45 mL/min (using the Cockcroft-Gault formula and actual body weight).Albumin ≥ 30 g/L.
• Baseline coagulation tests (within 7 days prior to the first dose) must meet the following criteria:International Normalized Ratio (INR) ≤ 1.5 × ULN (or ≤ 3 × ULN if on a stable dose of anticoagulant therapy).Partial Thromboplastin Time (PTT) or Activated Partial Thromboplastin Time (aPTT) ≤ 1.5 × ULN (or ≤ 3 × ULN if on a stable dose of anticoagulant therapy).
• Baseline urinalysis (within 7 days prior to the first dose) must meet the following criterion: Urine Protein (UPRO) \< 2+ or 24-hour urinary protein quantification \< 1 g.
• At least one measurable lesion as defined by RECIST v1.1 criteria. 14.Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1. 15.Life expectancy ≥ 3 months. 16.Male patients with partners of reproductive potential and female patients of childbearing potential must agree to use highly effective contraception throughout the treatment period and for 6 months thereafter.

You may not qualify if:

• All colorectal cancer patients must have confirmed MSS/pMMR status; patients with MSI-H/dMMR are excluded.
• History of hypersensitivity to any study drug components, including PD-1 inhibitors and pirfenidone.
• Female patients who are pregnant, lactating, or planning to become pregnant within 6 months after the last dose of the study drug.
• Known history or presence of active seizure disorder, active central nervous system metastases, spinal cord compression, carcinomatous meningitis, or leptomeningeal disease. Patients with newly identified brain or leptomeningeal metastases are excluded.
• Significant cardiovascular or cerebrovascular diseases with clinical importance.
• History of allergic predisposition, asthma, or atopic dermatitis.
• Patients with massive pleural effusion or massive ascites.
• Active autoimmune disease requiring systemic treatment (e.g., disease-modifying agents, corticosteroids, or immunosuppressants) within the past 2 years prior to the first dose. Replacement therapy is not considered systemic treatment.
• Known history of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation.
• Known or suspected hypersensitivity to the study drugs or any of their excipients.
• History of significant toxicity related to prior immune checkpoint inhibitor therapy or pirfenidone treatment that led to permanent discontinuation of the drug.
• Presence of unresolved \> Grade 1 toxicities (except for persistent Grade 2 alopecia, peripheral neuropathy, decreased hemoglobin, or hypomagnesemia) from any prior anticancer therapy.
• Active uncontrolled bleeding, known bleeding tendency, severe non-healing wounds, ulcers, fractures, or conditions such as esophageal/gastric varices requiring immediate intervention, or portal hypertension with high bleeding risk per investigator's assessment.
• History of intestinal obstruction (except if surgically cured or fully resolved) or risk of gastrointestinal perforation within 28 days prior to the first study dose.
• Current or recent (within 6 months) significant gastrointestinal disorders, including:

Sponsors & Collaborators

• Tao Zhang: lead

Study Sites (1)

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

Wuhan, Hubei, 430022, China

RECRUITING

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

pirfenidone; Radiation Dose Hypofractionation

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Dose Fractionation, Radiation; Radiotherapy Dosage; Radiotherapy; Therapeutics

Study Officials

• Tao Zhang, MD

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

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Zhenyu Lin, MD

CONTACT

027-83262683; whxhlzy@hust.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: June 8, 2026
• First Posted: June 12, 2026
• Study Start: December 1, 2025
• Primary Completion (Estimated): January 25, 2027
• Study Completion (Estimated): December 25, 2027
• Last Updated: June 12, 2026

Record last verified: 2025-11

Locations

CN (1)