Phase I/IIa AdCD40L Immunogene Therapy for Malignant Melanoma and Other Solid Tumors
Phase I/IIa AdCD40L Immunogene Therapy for Patients With Advanced Malignant Disease.
調査の概要
詳細な説明
In this phase I/II trial, immunostimulatory gene therapy (AdCD40L) will be investigated. In Part 1 patients with melanoma (n=6) will receive AdCD40L as mono therapy. In Part 2A, patients with melanoma (n=9) and patients with other solid tumors (n=6) will receive AdCD40L in combination with low dose cyclophosphamide. In Part 2B, patients with melanoma will receive AdCD40L in combination with one local radiotherapy and cyclophosphamide. AdCD40L is given by weekly injections of 2.5x10e11 VP, 4x; total dose 1x10e12 VP. A maximum of 30 patients will be included in this trial.
AdCD40L is an adenoviral nonreplicating vector carrying the human CD40L gene. AdCD40L infects tumor cells upon intratumoral injection and deliver the CD40L gene into the cells whereupon the virus is destroyed. CD40L is then expressed as a membrane-bound protein and interacts with the CD40 receptor expressed by for example dendritic cells (DCs) in the tumor area. DCs mature upon CD40/CD40L interactions and activates tumor-specific T cell responses.
研究の種類
入学 (実際)
段階
- フェーズ2
- フェーズ 1
連絡先と場所
研究場所
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Uppsala、スウェーデン、75185
- Uppsala University Hospital
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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:
- Histologically proven diagnosis of malignant solid cancer, ECOG 0-2.
- Disease progression on established treatments or patients not eligible to standard options.
- Signed informed consent must be obtained.
Exclusion Criteria:
- Pregnancy.
- Life expectancy less than 3 months.
- Any significant medical or psychiatric illness that would prevent the patient from giving informed consent or from following the study procedures.
- Patients with severe systemic autoimmune disease.
- Patients that do not consent to that tissue and blood samples are stored in a biobank.
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：なし
- 介入モデル：単一グループの割り当て
- 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：AdCD40L
Treatments once a week with 2.5x10e11 VP AdCD40L, maximum 4 treatments (total dose 1x10e12 VP).
If no effect in less than 2 out of 6 melanoma patients, the following 9 melanoma patients and 6 patients with other solid tumors will receive preconditioning therapy 1-2 days prior to first and last treatment with 300mg/m2 cyclophosphamid.
The next 9 melanoma patients will receive one local radiotherapy.
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Adenoviral serotype 5 vector, E1/E3 deleted.
Human CD40L gene insert driven by RSV promoter.
Vector diluted in infusion solution, 500uL solution containing 2.5x10e11 VP is intratumorally injected/treatment.
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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 |
|---|---|---|
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All cause adverse events
時間枠：during 10 weeks
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Adverse events will be documented such as inflammation, fever, pain, changes in blood pressure, pulse etc.
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during 10 weeks
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Immune reactions to adenovirus and spreading of vector
時間枠：during 10 weeks
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Immune reactions to adenovirus will be measured by evaluating the increase of anti-adenoviral antibodies in the patients at different time points using an ELISA.
Spreading of vector will be evaluated by real time PCR to detect adenovirus vector copies in blood (plasma and erythrocyte fraction).
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during 10 weeks
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二次結果の測定
結果測定 |
時間枠 |
|---|---|
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Tumor burden as measured by PET/CT and whole body MR
時間枠：At enrollment, week 5 and week 9
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At enrollment, week 5 and week 9
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協力者と研究者
スポンサー
捜査官
- スタディチェア：Thomas H Tötterman, MD, PhD、Uppsala University
- 主任研究者：Gustav Ullenhag, MD, PhD、Uppsala University Hospital
- スタディディレクター：Angelica SI Loskog, PhD、Uppsala University
出版物と役立つリンク
研究記録日
主要日程の研究
研究開始
一次修了 (実際)
研究の完了 (実際)
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 (見積もり)
学習記録の更新
投稿された最後の更新 (見積もり)
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。