Paricalcitol Versus Pirfenidone for Improving Surgical Resectability in Patients With Peritoneal Cancer (RANDY 1A)
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.
調査の概要
状態
介入・治療
詳細な説明
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.
研究の種類
入学 (推定)
段階
- フェーズ2
連絡先と場所
研究連絡先
- 名前：Patrick Wagner, MD
- 電話番号：412-359-3731
- メール：patrick.wagner@ahn.org
研究連絡先のバックアップ
- 名前：AHN Clinical Trial Contact
- 電話番号：412-359-3731
- メール：clinicaltrials@ahn.org
参加基準
適格基準
就学可能な年齢
健康ボランティアの受け入れ
受講資格のある性別
説明
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
研究計画
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：処理
- 割り当て：ランダム化
- 介入モデル：並列代入
- マスキング：なし（オープンラベル）
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
|
実験的：Paricalcitol Arm
Participants receive oral paricalcitol once daily for 12 weeks concurrently with standard systemic chemotherapy. |
Oral, 2 mcg once daily for 12 weeks |
|
実験的：Pirfenidone Arm
Participants receive oral pirfenidone three times daily for 12 weeks (with initial dose titration) concurrently with standard systemic chemotherapy. |
Oral, titrated up to 801 mg three times daily (total daily dose: 2403 mg/day) with food for 12 weeks. |
この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Paricalcitol Efficacy
時間枠：12 weeks from treatment initiation
|
Proportion of patients achieving a clinicopathologic response (CPR) |
12 weeks from treatment initiation
|
|
Pirfenidone Efficacy
時間枠：12 weeks from treatment initiation
|
Proportion of patients achieving a clinicopathologic response (CPR) |
12 weeks from treatment initiation
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Severity of Treatment-Emergent Adverse Events for Paricalcitol [Safety]
時間枠：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]
時間枠：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
時間枠：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]
時間枠：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]
時間枠：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]
時間枠：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]
時間枠：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]
時間枠：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]
時間枠：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]
時間枠：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]
時間枠：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]
時間枠：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]
時間枠：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]
時間枠：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]
時間枠：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]
時間枠：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]
時間枠：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]
時間枠：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
|
協力者と研究者
スポンサー
捜査官
- 主任研究者：Patrick Wagner、AHN Health Network
研究記録日
主要日程の研究
研究開始 (推定)
一次修了 (推定)
研究の完了 (推定)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (実際)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
本研究に関する用語
キーワード
追加の関連 MeSH 用語
その他の研究ID番号
- 2026-077
個々の参加者データ (IPD) の計画
個々の参加者データ (IPD) を共有する予定はありますか?
IPD プランの説明
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
医薬品およびデバイス情報、研究文書
米国FDA規制医薬品の研究
米国FDA規制機器製品の研究
米国で製造され、米国から輸出された製品。
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