Paricalcitol Versus Pirfenidone for Improving Surgical Resectability in Patients With Peritoneal Cancer (RANDY 1A)

September 28, 2026 updated by: Patrick Wagner, MD, FACS

A Randomized Phase II Bayesian Pick-the-Winner Clinical Trial Investigating the Efficacy of Fibrosis-Modulating Agents (Paricalcitol and Pirfenidone) in Improving Surgical Resectability in Patients With Peritoneal Carcinomatosis Ineligible for Definitive Cytoreduction (Randy 1A)

The goal of this clinical trial is to learn if paricalcitol or pirfenidone can help make tumors removable by surgery in adults with peritoneal cancer who are currently unable to have their tumor removed.

The study aims to answer are whether paricalcitol or pirfenidone improve tumor response and tissue healing after 12 weeks of treatment, and which of these two drugs is more effective at helping participants become eligible for surgery. Researchers will compare paricalcitol to pirfenidone to see which drug works better and has a manageable safety profile.

Participants will take either paricalcitol or pirfenidone by mouth every day for 12 weeks while continuing their standard chemotherapy, visit the clinic regularly for checkups and lab tests, keep a daily diary to track their study medication, and undergo a surgical re-evaluation after treatment to see if their tumor can be removed.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

This is a single-center, randomized Phase II clinical trial designed to investigate the efficacy of repurposing fibrosis-modulating agents to improve surgical resectability in patients with peritoneal carcinomatosis. Peritoneal carcinomatosis is characterized by a challenging tumor microenvironment (TME) featuring extensive fibrosis and a high density of cancer-associated fibroblasts (CAFs). These elements create a dense desmoplastic barrier that impedes drug penetration, limits therapeutic efficacy, and frequently renders patients ineligible for definitive surgical cytoreduction.

To overcome these barriers, the trial evaluates two distinct anti-fibrotic agents: paricalcitol, a synthetic Vitamin D receptor agonist that promotes CAF quiescence and stromal remodeling, and pirfenidone, an oral anti-fibrotic agent that inhibits fibrosis by downregulating the TGF-β signaling pathway and collagen synthesis. Eligible participants are randomized in a 1:1 ratio to receive a 12-week course of either oral paricalcitol (2 mcg daily, titratable) or oral pirfenidone (titrated to 801 mg three times daily with food), administered concurrently with their ongoing standard systemic chemotherapy.

Study Type

Interventional

Enrollment (Estimated)

74

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Males or females, age 18 to <81 years at the time of consent
  • Biopsy-proven peritoneal carcinomatosis
  • Documented receipt of at least three months of standard systemic chemotherapy prior to initiation, with persistent disease
  • ECOG Performance Status of 0 or 1
  • Adequate organ function within 14 days prior to anti-fibrotic initiation
  • Negative serum pregnancy test for women of childbearing potential (WOCBP) within 7 days prior to initiation
  • Able to understand and provide written informed consent
  • Willingness and ability to comply with all study procedures

Exclusion Criteria:

  • Patients deemed eligible for definitive cytoreductive surgery

    • Current or recent (within 30 days) use of paricalcitol, pirfenidone, or Vitamin D supplementation above USDA-recommended daily dosage
    • Known allergy or medical contraindication to study drugs
    • Hypersensitivity to any of the study drugs or to any ingredient in the formulation
    • Receipt of any investigational drug within 30 days prior to initiation
    • Active pregnancy or lactation
    • Active smoking
    • Active brain metastases
    • Elevated Vitamin D level (>2x upper limit of normal)
    • Significant comorbidities including abnormal calcium/phosphate, history of serious drug-induced liver injury, severe cardiac conditions, patients with or predisposed to cardiac arrhythmias, or uncontrolled hypertension
    • Concomitant medications that, after review by the study pharmacist(s) and potential dose modification in accordance with prescribing guidelines, still pose an unmanageable drug-drug interaction or unacceptable safety risk with either study drug

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Paricalcitol Arm

Participants receive oral paricalcitol once daily for 12 weeks concurrently with standard systemic chemotherapy.
Drug: Paricalcitol

Oral, 2 mcg once daily for 12 weeks
Experimental: Pirfenidone Arm

Participants receive oral pirfenidone three times daily for 12 weeks (with initial dose titration) concurrently with standard systemic chemotherapy.
Drug: pirfenidone

Oral, titrated up to 801 mg three times daily (total daily dose: 2403 mg/day) with food for 12 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Paricalcitol Efficacy
Time Frame: 12 weeks from treatment initiation

Proportion of patients achieving a clinicopathologic response (CPR)
12 weeks from treatment initiation
Pirfenidone Efficacy
Time Frame: 12 weeks from treatment initiation

Proportion of patients achieving a clinicopathologic response (CPR)
12 weeks from treatment initiation

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Severity of Treatment-Emergent Adverse Events for Paricalcitol [Safety]
Time Frame: 16 weeks from treatment initiation

Maximum severity grade of treatment-emergent adverse events per participant, assessed on a scale from Grade 1 (mild) to Grade 5 (death) according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Higher grades indicate a more severe outcome.
16 weeks from treatment initiation
Severity of Treatment-Emergent Adverse Events for Pirfenidone [Safety]
Time Frame: 16 weeks from treatment initiation

Maximum severity grade of treatment-emergent adverse events per participant, assessed on a scale from Grade 1 (mild) to Grade 5 (death) according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Higher grades indicate a more severe outcome
16 weeks from treatment initiation
Incidence of Treatment-Emergent Adverse Events for Paricalcitol [Safety
Time Frame: 16 weeks from treatment initiation

Number of participants experiencing one or more treatment-emergent adverse events, as graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
16 weeks from treatment initiation
Incidence of Treatment-Emergent Adverse Events for Pirfenidone [Safety]
Time Frame: 16 weeks from treatment initiation

Number of participants experiencing one or more treatment-emergent adverse events, as graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
16 weeks from treatment initiation
Patient-Reported Quality of Life Outcomes Using the Medical Outcomes Study 20-Item Short-Form Health Survey (SF-20) for Paricalcitol [Tolerability]
Time Frame: 12 weeks

Assessment of patient-reported quality of life outcomes using the SF-20 questionnaire. Each subscale ranges from a minimum score of 0 to a maximum score of 100, where higher scores indicate a better health-related quality of life outcome.
12 weeks
Patient-Reported Quality of Life Outcomes Using the Medical Outcomes Study 20-Item Short-Form Health Survey (SF-20) for Pirfenidone [Tolerability]
Time Frame: 12 weeks

Assessment of patient-reported quality of life outcomes using the SF-20 questionnaire. Each subscale ranges from a minimum score of 0 to a maximum score of 100, where higher scores indicate a better health-related quality of life outcome.
12 weeks
Treatment Adherence Evaluated via Study Drug Diaries for Paricalcitol [Feasibility]
Time Frame: 12 weeks

Percentage of total prescribed doses taken based on study drug diaries (number of doses taken divided by total expected doses over 12 weeks).
12 weeks
Treatment Adherence Evaluated via Study Drug Diaries for Pirfenidone [Feasibility]
Time Frame: 12 weeks

Percentage of total prescribed doses taken based on study drug diaries (number of doses taken divided by total expected doses over 12 weeks).
12 weeks
Molecular Biomarker Analysis of Treatment Response in Research Blood Samples for Paricalcitol [Efficacy]
Time Frame: 12 weeks

Evaluation of molecular correlates of treatment response using research blood samples collected at baseline and post-treatment.
12 weeks
Molecular Biomarker Analysis of Treatment Response in Research Blood Samples for Pirfenidone [Efficacy]
Time Frame: 12 weeks

Evaluation of molecular correlates of treatment response using research blood samples collected at baseline and post-treatment.
12 weeks
Molecular Biomarker Analysis of Treatment Response in Research Blood Samples for Paricalcitol [Efficacy]
Time Frame: 12 weeks

Evaluation of circulating biomarkers of treatment response using research blood samples collected at baseline and post-treatment.
12 weeks
Molecular Biomarker Analysis of Treatment Response in Research Blood Samples for Pirfenidone [Efficacy]
Time Frame: 12 weeks

Evaluation of circulating biomarkers of treatment response using research blood samples collected at baseline and post-treatment.
12 weeks
Biomarker Analysis of Treatment Response in Tissue Biopsy Samples for Pirfenidone [Efficacy]
Time Frame: 12 weeks

Quantitative assessment of treatment response using baseline and post-treatment archival tissue biopsy samples, measuring changes in Ki-67 positive tumor cells
12 weeks
Biomarker Analysis of Treatment Response in Tissue Biopsy Samples for Paricalcitol [Efficacy]
Time Frame: 12 weeks

Quantitative assessment of treatment response using baseline and post-treatment archival tissue biopsy samples, measuring changes in Ki-67 positive tumor cells
12 weeks
Biomarker Analysis of Treatment Response in Tissue Biopsy Samples for Paricalcitol [Efficacy]
Time Frame: 12 weeks from treatment initiation

Quantitative assessment of treatment response using baseline and post-treatment archival tissue biopsy samples, measuring changes in density of Fibroblast Activation Protein-positive (FAP+)
12 weeks from treatment initiation
Biomarker Analysis of Treatment Response in Tissue Biopsy Samples for Pirfenidone [Efficacy]
Time Frame: 12 weeks from treatment initiation

Quantitative assessment of treatment response using baseline and post-treatment archival tissue biopsy samples, measuring changes in density of Fibroblast Activation Protein-positive (FAP+)
12 weeks from treatment initiation
Biomarker Analysis of Treatment Response in Tissue Biopsy Samples for Paricalcitol [Efficacy]
Time Frame: 12 weeks from treatment initiation

Quantitative assessment of treatment response using baseline and post-treatment archival tissue biopsy samples measuring changes in collagen density (quantified via Sirius Red or Masson's Trichrome staining).
12 weeks from treatment initiation
Biomarker Analysis of Treatment Response in Tissue Biopsy Samples for Pirfenidone [Efficacy]
Time Frame: 12 weeks from treatment initiation

Quantitative assessment of treatment response using baseline and post-treatment archival tissue biopsy samples measuring changes in collagen density (quantified via Sirius Red or Masson's Trichrome staining).
12 weeks from treatment initiation

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Patrick Wagner, MD, FACS

Investigators

  • Principal Investigator: Patrick Wagner, AHN Health Network

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

September 1, 2026

Primary Completion (Estimated)

September 1, 2030

Study Completion (Estimated)

November 1, 2030

Study Registration Dates

First Submitted

September 16, 2026

First Submitted That Met QC Criteria

September 28, 2026

First Posted (Actual)

October 5, 2026

Study Record Updates

Last Update Posted (Actual)

October 5, 2026

Last Update Submitted That Met QC Criteria

September 28, 2026

Last Verified

September 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2026-077

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

Sharing of data or bio-specimens is not currently planned and will require a separate IRB application and a Material Transfer Agreement (MTA) or Data Use Agreement (DUA), as applicable, in the event that such plans arise in the future

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Subscribe