A Study to Investigate the Efficacy and Safety of Alpha1H as a Neoadjuvant Therapy in Participants With Low- to Intermediate-Risk/Low-Grade Papillary Non-Muscle Invasive Bladder Cancer
A Randomized Phase III Study to Investigate the Efficacy and Safety of Alpha1H as a Neoadjuvant Therapy in Participants With Low- to Intermediate-Risk/Low-Grade Papillary Non-Muscle Invasive Bladder Cancer
The goal of this clinical trial is to learn if the drug Alpha1H works to treat low-to-intermediate risk non-muscle-invasive bladder cancer in adults. It will also learn about the safety of drug Alpha1H.
The main questions it aims to answer are:
- Does giving drug Alpha1H before surgery lower the risk of cancer returning or worsening compared to standard care alone?
- Is drug Alpha1H safe and well-tolerated by participants? Researchers will compare participants receiving drug Alpha1H before standard surgery to participants receiving standard care alone to see if drug Alpha1H lowers the risk of cancer returning or progressing.
Participants will:
- Be randomly assigned to receive either drug Alpha1H before surgery or standard care alone.
- Receive drug Alpha1H directly into the bladder 6 times over about 1 month if assigned to the Alpha1H group.
- Hold the liquid in the bladder for up to 2 hours during each visit.
- Undergo standard surgery through the urethra (TURBT) to remove remaining tumor tissue.
- Visit the clinic regularly for follow-up checkups (including bladder examinations and urine tests) to check if the cancer returns.
- Fill out questionnaires about their quality of life.
調査の概要
状態
研究の種類
入学 (推定)
段階
- フェーズ 3
連絡先と場所
研究連絡先
- 名前：Catharina Svanborg, MD, PhD.
- 電話番号：+46709426549
- メール：catharina.svanborg@med.lu.se
研究連絡先のバックアップ
- 名前：Petr Bouska
- 電話番号：+420773076076
- メール：pe.bouska@gmail.com
研究場所
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Prague、チェコ、15000
- 募集
- Fakultni nemocnice Motol a Homolka
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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:
- Signed and dated informed consent.
- Low- or intermediate-risk non-muscle-invasive bladder cancer (NMIBC) meeting one of the following definitions:
- Low-risk NMIBC: Primary, solitary, Ta, low-grade, 0.5 cm to 3 cm.
- Intermediate-risk NMIBC (low-to-intermediate risk subgroup per IBCG classification):
- Primary multifocal (<10 lesions), Ta, low-grade, 0.5 cm to 3 cm;
- Recurrent solitary, Ta, low-grade, 0.5 cm to 3 cm; or
- Recurrent multifocal (<10 lesions), Ta, low-grade, >1 year after previous recurrence.
- Men and women aged 18 years or older.
- Negative pregnancy test at screening for women of childbearing potential.
- Women of childbearing potential must agree to use highly effective contraception methods throughout study participation; men of childbearing potential must refrain from donating sperm during the study.
- Ability to retain bladder contents for 2 hours.
Exclusion Criteria:
- Patient with non-papillary tumor appearance at the time of initial cystoscopy.
- Previous history of T1 or high-grade disease in recurrent tumors.
- Patients with T1 or high-grade non-muscle invasive papillary bladder cancer (NMIBC).
- Previous intravesical BCG immunotherapy.
- Patients with any other cancer diagnosis within the last 5 years (except for skin basalioma).
- Acute urinary tract infection requiring antibiotic treatment.
- Prior radiotherapy or systemic chemotherapy.
- WHO performance status of 3 or 4.
- Any other investigational agent or non-marketed product within one month prior to Visit 1 and during the trial.
- Known active HIV infection, defined as detectable HIV viral load at screening.
- Active hepatitis B virus (HBV) infection, defined as hepatitis B surface antigen (HBsAg) positivity with detectable HBV DNA at screening.
- Active hepatitis C virus (HCV) infection, defined as anti-HCV antibody positivity with detectable HCV RNA at screening in a patient not on stable antiviral treatment.
- Any concurrent illness that may render a participant ineligible or limit compliance with study requirements.
- Previously enrolled in this trial.
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 |
|---|---|
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実験的：Alpha1H
Participants receive 6 intravesical instillations of Alpha1H over approximately 1 month prior to transurethral resection of bladder tumor (TURBT). |
Administered via intravesical instillation directly into the urinary bladder. Participants in the experimental group receive a total of 6 instillations on Days 1, 3, 5, 8, 15, and 22 over approximately 1 month prior to TURBT. During each treatment, participants are asked to retain the solution in the bladder for up to 2 hours. Standard endoscopic surgical procedure performed through the urethra to resect and remove papillary bladder tumor tissue. Performed approximately 30 days after study entry (on Visit 8). Resected tumor tissue is collected for histopathology and central analysis. A single early intravesical instillation of standard-of-care chemotherapy (epirubicin, mitomycin, or gemcitabine) administered into the urinary bladder shortly following TURBT surgery in accordance with local institutional guidelines. |
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アクティブコンパレータ：Standard of Care
Participants receive standard of care consisting of transurethral resection of bladder tumor (TURBT) followed by a single early intravesical instillation of standard chemotherapy. |
Standard endoscopic surgical procedure performed through the urethra to resect and remove papillary bladder tumor tissue. Performed approximately 30 days after study entry (on Visit 8). Resected tumor tissue is collected for histopathology and central analysis. A single early intravesical instillation of standard-of-care chemotherapy (epirubicin, mitomycin, or gemcitabine) administered into the urinary bladder shortly following TURBT surgery in accordance with local institutional guidelines. |
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 |
時間枠 |
|---|---|
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Event-Free Survival (EFS)
時間枠：From randomization until the occurrence of an EFS event or study completion, assessed at 3, 6, 9 (optional), and 12 months post-randomization, and every 6 months thereafter for up to 3 years.
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From randomization until the occurrence of an EFS event or study completion, assessed at 3, 6, 9 (optional), and 12 months post-randomization, and every 6 months thereafter for up to 3 years.
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二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Complete Response (CR) Rate
時間枠：Day 30 (±5 days), prior to TURBT
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Day 30 (±5 days), prior to TURBT
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Overall Survival (OS)
時間枠：From randomization through study completion (assessed at 3, 6, 9 [optional], and 12 months, and every 6 months thereafter for up to 3 years).
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From randomization through study completion (assessed at 3, 6, 9 [optional], and 12 months, and every 6 months thereafter for up to 3 years).
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Incidence and Severity of Adverse Events (AEs)
時間枠：From Visit 1 (Screening) through Visit 9 (Day 40/50) and follow-up period (up to 3 years)
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From Visit 1 (Screening) through Visit 9 (Day 40/50) and follow-up period (up to 3 years)
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Tumor Response (Morphological and Cellular)
時間枠：Baseline (Day 1) to Day 30 (±5 days)
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Assessed as: (1) change in papillary tumor size (% reduction from baseline); (2) tumor cell shedding in urine (cells/mL); (3) apoptosis in shed cells (% TUNEL-positive cells); (4) Alpha1H uptake in shed cells (% Alpha1H-positive cells). Each parameter reported separately. |
Baseline (Day 1) to Day 30 (±5 days)
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Tumor Gene Expression
時間枠：Baseline (Day 1) to Day 30 (±5 days)
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Assessed by RNA sequencing (whole transcriptome) in tumor tissue and urine RNA. Reported as number of differentially expressed cancer-related genes and pathways between the Alpha1H and SOC arms. |
Baseline (Day 1) to Day 30 (±5 days)
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Urinary Biomarkers and Immune Response
時間枠：Day 1, 3, 5, 8, 15, and 22 (pre- and post-instillation), and Day 30 (±5 days)
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Assessed by proteomic profiling of urine samples. Reported as change in concentration (pg/mL) of cytokines, chemokines, and interferons between pre- and post-instillation samples, compared between the Alpha1H and SOC arms. |
Day 1, 3, 5, 8, 15, and 22 (pre- and post-instillation), and Day 30 (±5 days)
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Change in Quality of Life (QoL) as Assessed by the QLQ-NMIBC24 Questionnaire
時間枠：From Visit 1 (Screening) through follow-up visits (up to 3 years)
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Quality of life will be assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Non-Muscle-Invasive Bladder Cancer Module (EORTC QLQ-NMIBC24), a 24-item, disease-specific patient-reported outcome instrument. Each domain score is linearly transformed to range from 0 to 100. On functional scales (e.g., sexual function), higher scores indicate better functioning; on symptom-related scales (e.g., urinary symptoms, future perspective), higher scores indicate greater symptom burden. Scores are calculated per the EORTC scoring manual. |
From Visit 1 (Screening) through follow-up visits (up to 3 years)
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協力者と研究者
スポンサー
研究記録日
主要日程の研究
研究開始 (実際)
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
- HP003-001
- 2026-525531-16-00 (Ctis)
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?
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
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