Multi-peptide Vaccination and Bispecific PSMAxCD3 Antibody Treatment in Patients With Prostate Cancer (ImmProCure)
Randomized Phase II Study of Multi-peptide Vaccination and Bispecific PSMAxCD3 Antibody Treatment in Patients With Biochemical Relapse of Prostate Cancer
This trial is a phase II, randomized, open label study designed to evaluate safety, tolerability and efficacy of CC-1, a bispecific antibody (bsAb) with PSMAxCD3 specificity, and of VACXS15-PC01, a prostate cancer (PC)-specific multi-peptide vaccine, both administered as single agent or in combination to patients affected with biochemical recurrence (BCR) of PC after local therapy with curative intent. Patients will not receive other treatments during trial participation.
調査の概要
詳細な説明
CC-1 contains a PSMA binder with particular reactivity in PC and also binds to tumor vessels, thereby allowing for a dual mode of anti-cancer action. CC-1 was developed in a novel format which not only prolongs serum half-life, but most importantly reduces off-target T cell activation with expected fewer side effects. The multi-peptide vaccine VAC-XS15-PC01 is composed of 10 HLA-restricted antigens, comprising immunopeptidome-defined PC-associated epitopes, adjuvanted with the TLR1/2 ligand XS15 emulsified in Montanide ISA 51 VG.
The study entails three-arms: (1) the multi-peptide vaccine VAC-XS15-PC01 alone, (2) PSMAxCD3 bispecific antibody CC-1 alone and (3) combinatorial treatment of CC-1 and VAC-XS15-PC01. Up to 84 patients are recruited (n = up to 28 per arm) and patients are randomly assigned 1:1:1 (drop-out rate of 15% anticipated). A translational research program comprising, among others, a strict evaluation of prostate specific antigen (PSA) course integrated with analysis of CC-1 induced immune response and immunogenicity of VAC-XS15-PC01 serves to detect early signs of efficacy. Furthermore, safety of the investigational medical products is evaluated, and tolerability of their combination are assessed.
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：Susanne Jung, Dr. med.
- 電話番号：+49 (0)7071-29 83275
- メール：kketi@med.uni-tuebingen.de
研究場所
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Baden-Wurttemberg
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Heidelberg、Baden-Wurttemberg、ドイツ、69120
- まだ募集していません
- NCT Studienzentrale; Nationales Centrum für Tumorerkrankungen (NCT) Heidelberg
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コンタクト：
- Stefanie Zschaebitz, Dr. med.
- 電話番号：+49 (0)6221-56-35950
- メール：kketi@med.uni-tuebingen.de
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Tübingen、Baden-Wurttemberg、ドイツ、72076
- 募集
- CCU Transltional Immunolgy, University Hospital Tübingen
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コンタクト：
- Susanne Jung, Dr. med.
- 電話番号：+49 (0)7071-29 83275
- メール：kketi@med.uni-tuebingen.de
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Beriln
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Berlin、Beriln、ドイツ、12203
- まだ募集していません
- Charité - Universitätsmedizin Berlin, Campus Benjamin Franklin - Studienzentrale Onkologie
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コンタクト：
- Sebastian Ochsenreither, Prof. Dr.
- 電話番号：+49 30 450 613 483
- メール：kketi@med.uni-tuebingen.de
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North Rhine-Westphalia
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Essen、North Rhine-Westphalia、ドイツ、45147
- まだ募集していません
- Universitätsklinikum Essen, Abteilung Urologie
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コンタクト：
- Darr Christopher, Dr. med.
- 電話番号：+49 (0)201 723-3210
- メール：kketi@med.uni-tuebingen.de
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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:
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Understand and voluntarily sign an IC document prior to any study related assessments/procedures
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Understand and voluntarily sign an IC document prior to any study related assessments/procedures
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Patient is able to understand and comply with the protocol for the duration of the study including treatment and scheduled visits and examinations
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Men aged ≥ 18 and ≤80 years
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Histologic diagnosis of prostatic adenocarcinoma
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Biochemical recurrence (BCR): PSA recurrence after treatment with curative intent; PSA ≥0.2 ng/mL or PSA > nadir + 2 ng/mL (after definitive RT), with two increasing PSA values prior to study treatment; AND no distant metastasis upon PSMA-PET imaging
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Patients are ineligible to receive available treatment alternatives
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Low risk of rapid disease progression, defined as:
o PSA-DT > 1 year AND pathological ISUP grade < 4 for men with prior RP OR Interval to BCR > 18 months AND biopsy ISUP grade < 4 for men with prior radiation therapy
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In case of second relapse PSA-DT > 9 months
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Eastern Cooperative Oncology Group (ECOG) performance status ≤1
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Exclusion Criteria:
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• PSA >5 ng/mL (at screening)
- Patients who are receiving or have previously received androgen deprivation treatment.
Except testosterone has recovered to normal levels: patients who have previously received anti-hormonal treatment testosterone must be >12 nmol/l.
- Patients who are planned to or are undergoing salvage therapy (e.g. radiation)
- Clinically significant xerostomia (dry mouth >1grade according to CTCAE v6.0)
- Untreated current or prior distant metastasis of PC
- Other malignancy within the last 2 years except: adequately treated non-melanoma skin cancer and non-muscle invasive bladder cancer.
- Concurrent or previous treatment within 30 days in another interventional clinical trial with an investigational anti-cancer therapy
- Clinical signs of active infection (> grade 2 according to CTCAE v6.0)
- History of HIV infection
- Viral active or chronic hepatitis (HBV or HCV)
- Autoimmune disease that requires or has required treatment with systemic immunosuppressive treatments, except low dose corticosteroids (< 10 mg/ day), in the past 1 year
- Ongoing relevant CNS pathology (e.g. seizure, paresis, aphasia, cerebrovascular ischemia, severe brain injuries, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, psychosis, coordination or movement disorder)
- Epilepsy requiring pharmacologic treatment
- Major surgery within 4 weeks of starting study treatment. Patients must have recovered from any effects of major surgery.
- Heart failure NYHA III/IV
- Severe obstructive or restrictive ventilation disorder
- Known intolerance to CC-1, or other immunoglobulin drug products as well as hypersensitivity to any of the excipients present in the respective drug products (CC-1, VAC-XS15-PC01)
- Refrain from blood donation during the course of the study
- Male patients have to refrain from sperm donations for 6 months after last IMP
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 |
|---|---|
|
アクティブコンパレータ：Multi-peptide vaccine VAC-XS15-PC01
The vaccine VAC-XS15-PC01 consists of 300 µg of each of 10 PC-associated peptides. The vaccine cocktail (final volume 500 µL) will be administered subcutaneously (SC), adjuvanted with the TLR1/2 ligand XS15 (50 µg) and emulsified in Montanide ISA 51 VG at a 1:1 ratio. A total of three vaccinations are planned in Arm 1, administered 4 weeks apart from each other. |
The vaccine VAC-XS15-PC01 consists of 300 µg of each of 10 PC-associated peptides. The vaccine cocktail (final volume 500 µL) will be administered subcutaneously (SC), adjuvanted with the TLR1/2 ligand XS15 (50 µg) and emulsified in Montanide ISA 51 VG at a 1:1 ratio. A total of three vaccinations are planned in Arm 1, administered 4 weeks apart from each other. |
|
アクティブコンパレータ：PSMAxCD3 bispecific antibody CC-1
CC-1 is applied subcutaneously once per week for 12 weeks in Arm 2. Due to priming doses up to 14 applications are planned. |
CC-1 is applied subcutaneously once per week for 12 weeks in Arm 2. Due to priming doses up to 14 applications are planned. |
|
実験的：PSMAxCD3 bispecific antibody CC-1 + Multi-peptide vaccine VAC-XS15-PC01
The vaccine VAC-XS15-PC01 consists of 300 µg of each of 10 PC-associated peptides. The vaccine cocktail (final volume 500 µL) will be administered subcutaneously (SC), adjuvanted with the TLR1/2 ligand XS15 (50 µg) and emulsified in Montanide ISA 51 VG at a 1:1 ratio. A total of three vaccinations are planned in Arm 3, administered 4 weeks apart from each other. CC-1 is applied subcutaneously once per week for 12 weeks in Arm 3. Due to priming doses up to 14 applications are planned. |
The vaccine VAC-XS15-PC01 consists of 300 µg of each of 10 PC-associated peptides. The vaccine cocktail (final volume 500 µL) will be administered subcutaneously (SC), adjuvanted with the TLR1/2 ligand XS15 (50 µg) and emulsified in Montanide ISA 51 VG at a 1:1 ratio. A total of three vaccinations are planned in Arm 1, administered 4 weeks apart from each other. CC-1 is applied subcutaneously once per week for 12 weeks in Arm 2. Due to priming doses up to 14 applications are planned. |
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 |
|---|---|---|
|
PSA response defined as ≥50% reduction in PSA at FU1 compared to baseline.
時間枠：Screening: 21 days before Cycle (C1);C1: Day (D) -1, D0 to D3, D8, D15, and D22; C2-3: D1, D8, D15, and D22 (each cycle is 22 days); End of Treatment (EOT): D29 of C3; Follow-Up 1-5: every 30 days after the EOT; End of study (EOS): 12 months after EOT
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PSA serum levels [ng/ml] are determined during screening, before every treatment, and then every 30 days until end of follow up. PSA serum levels for one study patient should be locally assessed in the same lab during the whole study treatment. Furthermore, 5ml serum are taken and should be processed locally and stored at -80 °C at the study site. Tübingen for central assessment of PSA. |
Screening: 21 days before Cycle (C1);C1: Day (D) -1, D0 to D3, D8, D15, and D22; C2-3: D1, D8, D15, and D22 (each cycle is 22 days); End of Treatment (EOT): D29 of C3; Follow-Up 1-5: every 30 days after the EOT; End of study (EOS): 12 months after EOT
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協力者と研究者
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
この情報は、Web サイト clinicaltrials.gov から変更なしで直接取得したものです。研究の詳細を変更、削除、または更新するリクエストがある場合は、register@clinicaltrials.gov。 までご連絡ください。 clinicaltrials.gov に変更が加えられるとすぐに、ウェブサイトでも自動的に更新されます。