Weekly Doses of Cilengitide and Paclitaxel in Treating Patients With Advanced Solid Tumors That Cannot Be Removed by Surgery
A Phase I, Open Label, Dose Escalation Study of the Safety, Tolerability and Pharmacokinetic Properties of the Combination of Cilengitide and Paclitaxel in Patients With Advanced Solid Malignancies
調査の概要
状態
詳細な説明
PRIMARY OBJECTIVES:
I. To determine the maximally tolerated dose (MTD) of cilengitide and paclitaxel at weekly dose schedule. (Cohort I) II. To describe the toxicities associated with cilengitide and paclitaxel. III. To describe any antitumor activity of cilengitide and paclitaxel at weekly dose schedule.
IV. To characterize pharmacokinetics (PK) of cilengitide and paclitaxel with the proposed schedule and correlate PK parameters to clinical outcome. (Cohort I) V. To examine the effect of cilengitide and paclitaxel on circulating cysteine-rich, angiogenic inducer, 61 (Cyr61) using a novel "sandwich enzyme-linked immunosorbent assay (ELISA)" and to correlate this effect with clinical response. (Cohort II) VI. To evaluate the information obtained through use of items from the Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) in Phase I studies.
VII. To determine if tumor tissue expression of alpha v beta 3 (αvβ3) and CYR61 correlate with therapeutic response to cilengitide with paclitaxel. (Cohort II)
OUTLINE: This is a dose-escalation study of cilengitide.
Patients receive cilengitide intravenously (IV) over 1 hour on days* 1, 8, and 15 and paclitaxel IV over 1 hour on days 1, 8, and 15. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
NOTE: *Some patients receive cilengitide IV over 1 hour on days 1, 2, 8, 9, 15, and 16.
After completion of study treatment, patients are followed up for 3 months.
研究の種類
入学 (実際)
段階
- フェーズ 1
連絡先と場所
研究場所
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Arizona
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Scottsdale、Arizona、アメリカ、85259
- Mayo Clinic in Arizona
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Florida
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Jacksonville、Florida、アメリカ、32224-9980
- Mayo Clinic in Florida
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Minnesota
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Rochester、Minnesota、アメリカ、55905
- Mayo Clinic
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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:
- Histologic proof of cancer that is now unresectable (solid tumors, excluding lymphoma)
For Cohort II only:
- Histologic adenocarcinoma of the breast with manifestations of metastatic cancer or locally advanced, unresectable cancer
- Estrogen, progesterone, and human epidermal growth factor receptor 2 (HER2) receptor negative disease per local standards
- Refractory to taxanes which is defined as one of the following:
- Having relapsed during or within 12 months of completing adjuvant paclitaxel or docetaxel
- Disease progression while on any taxane in the locally advanced, unresectable or metastatic breast cancer setting
- Ability and willingness to undergo biopsy for biomarker testing prior to start of treatment
- Disease must be measurable by imaging-based evaluation per Response Evaluation Criteria in Solid Tumors (RECIST) criteria (v1.1)
- Up to 5 prior regimens of chemotherapy for metastatic disease are allowed
- Absolute neutrophil count (ANC) >= 1500/μL
- Hemoglobin (Hgb) >= 9 g/dL
- Platelets (PLT) >= 100,000/μL
- Total bilirubin =< 1.5 x upper limit of normal (ULN)
- Aspartate aminotransferase (AST) =< 3 x ULN or AST =< 5 x ULN if liver involvement
- Creatinine =< 1.5 x ULN
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, or 1 (or Karnofsky performance status [KPS] > 70)
- Ability to provide informed consent
- Willingness to return to the enrolling Mayo Clinic institution for follow-up
- Life expectancy >= 12 weeks
- All patients: Willingness to provide blood samples for the mandatory correlative research component
- For Cohort II, tissue biopsies are mandatory
- Women of childbearing potential only: negative serum pregnancy test done =< 7 days prior to registration, for women of childbearing potential including women within 2 years of post-menopause
Exclusion Criteria:
- Known standard therapy for the patient's disease that is potentially curative or definitely capable of extending life expectancy
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
Any of the following prior therapies:
- Chemotherapy =< 21 days prior to registration
- Mitomycin C/nitrosoureas =< 42 days prior to registration
- Immunotherapy =< 14 days prior to registration
- Biologic therapy =< 14 days prior to registration
- Prior investigational therapy =< 28 days prior to registration
Full field radiation therapy =< 28 days prior to registration or limited field radiation therapy < 14 days prior to registration
- Full field radiation encompasses the entire area of known disease involvement and surrounding uninvolved but at-risk areas, e.g. subtotal nodal (mantle and upper abdomen) or total nodal irradiation
- Limited field radiation is restricted to treating only the known areas of clinical disease, e.g. involved-field therapy for lymphoma
- Major surgery (i.e., laparotomy) =< 4 weeks prior to registration; minor surgery =< 2 weeks prior to registration; Note: insertion of a vascular access device is not considered major or minor surgery in this regard
- Unresolved toxicities from prior therapy with the exception of alopecia that have not resolved to =< grade 1, unless the patient has a chronic, stable =< grade 2 toxicity that would not interfere with the evaluation of the study agents
- New York Heart Association classification III or IV
- Central nervous system (CNS) metastases or seizure disorder; Note: CNS metastases are allowed if previously treated and stable for at least 4 weeks
Any of the following:
- Pregnant women
- Nursing women
- Men or women of childbearing potential who are unwilling to employ adequate contraception (condoms, diaphragm, injections, intrauterine device [IUD], or abstinence, etc.); oral, implantable, or injectable contraceptives may be affected by cytochrome P450 interactions, and are therefore not considered effective for this study
- Other concurrent chemotherapy, immunotherapy, radiotherapy, or any ancillary therapy considered investigational (utilized for a non-Food and Drug Administration [FDA]-approved indication and in the context of a research investigation)
- Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens
- Immunocompromised patients (other than that related to the use of corticosteroids) including patients known to be human immunodeficiency virus (HIV) positive on highly active antiretroviral therapy (HAART) therapy
- Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm
- Other active malignancy =< 3 years prior to registration; EXCEPTIONS: nonmelanotic skin cancer or carcinoma-in-situ of the cervix; Note: if there is a history of prior malignancy, they must not be receiving other specific treatment for their cancer
- History of myocardial infarction =< 6 months prior to registration, or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias
- Uncontrolled hypertension, labile hypertension of history of poor compliance with antihypertensive medication
- Patients with active, bleeding diathesis
- Non-disease related- major surgery, =< 28 days or minor surgery =< 7 days prior to registration
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:Treatment (cilengitide, paclitaxel)
Patients receive cilengitide IV over 1 hour on days* 1, 8, and 15 and paclitaxel IV over 1 hour on days 1, 8, and 15. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. NOTE: *Some patients receive cilengitide IV over 1 hour on days 1, 2, 8, 9, 15, and 16. |
相関研究
相関研究
与えられた IV
他の名前:
与えられた IV
他の名前:
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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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治療に関連する毒性が生じるまでの時間
時間枠:3ヶ月まで
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3ヶ月まで
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治療関連のグレード 3+ 毒性までの時間
時間枠:3ヶ月まで
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3ヶ月まで
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進行までの時間
時間枠:3ヶ月まで
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3ヶ月まで
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治療失敗までの時間
時間枠:登録から進行、許容できない毒性、または患者による参加継続の拒否の文書化までの時間、最大 3 か月で評価
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登録から進行、許容できない毒性、または患者による参加継続の拒否の文書化までの時間、最大 3 か月で評価
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Best response, defined to be complete response (CR) or partial response (PR) as assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
時間枠:From start of the treatment until disease progression/recurrence, assessed up to 3 months
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Responses will be summarized by simple descriptive summary statistics delineating complete and partial responses as well as stable and progressive disease in this patient population (overall and by tumor group).
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From start of the treatment until disease progression/recurrence, assessed up to 3 months
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Change in Cyr61 expression levels (Cohort II)
時間枠:Baseline to up to 3 months
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At the end of each cycle, the percent change in serum Cyr61 expression from pre-treatment levels will be determined for each patient.
For each patient, a times series plot of the percent change in serum Cyr61 expression from pre-treatment levels will be constructed and visually inspected for trends across time as well as for differences between those who respond to treatment (CR or PR by RECIST criteria) and those who do not.
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Baseline to up to 3 months
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Change in Cyr61 expression levels (Cohort II)
時間枠:Baseline to 21 days
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A Wilcoxon rank sum test will be used to assess the percent change in Cyr61expression level after one cycle of treatment from pretreatment levels differs between those who progress within 120 days (within the first 6 cycles of treatment) and those who remain progression-free at least 120 days.
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Baseline to 21 days
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Incidence of grade 3+ adverse events, as graded using NCI CTCAE v 4.0
時間枠:Up to 3 months
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The number and severity of grade 3+ adverse events (overall, by dose-level, and by tumor group) will be tabulated and summarized in this patient population.
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Up to 3 months
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Incidence of hematologic toxicity, including thrombocytopenia, neutropenia, and leukopenia, evaluated via the ordinal CTC
時間枠:Up to 3 months
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Assessed using continuous variables as the outcome measures (primarily nadir) as well as categorization via CTC standard toxicity grading.
Overall toxicity incidence as well as toxicity profiles by dose level, patient and tumor site will be explored and summarized.
Frequency distributions, graphical techniques and other descriptive measures will form the basis of these analyses.
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Up to 3 months
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Incidence of non-hematologic toxicity, evaluated via the ordinal Common Toxicity Criteria (CTC)
時間枠:Up to 3 months
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Overall toxicity incidence as well as toxicity profiles by dose level, patient and tumor site will be explored and summarized.
Frequency distributions, graphical techniques and other descriptive measures will form the basis of these analyses.
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Up to 3 months
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MTD of cilengitide and paclitaxel, defined as the dose level below the lowest dose that induces dose-limiting toxicity in at least 1/3 of patients as graded using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0
時間枠:3 weeks
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3 weeks
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Number of all adverse events, graded according to the NCI CTCAE v4.0
時間枠:Up to 3 months
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The number of all adverse events (overall, by dose-level, and by tumor group) will be tabulated and summarized in this patient population.
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Up to 3 months
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Overall survival (OS) (Cohort II)
時間枠:The time of registration to death due to any cause, assessed up to 3 months
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Kaplan-Meier method will be used to estimate the distribution of OS time.
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The time of registration to death due to any cause, assessed up to 3 months
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Progression-free survival (PFS) (Cohort II)
時間枠:The time of registration to documentation of disease event where a disease event is local/regional/distant progression, contralateral breast disease, second primary disease or death due to any cause, assessed up to 3 months
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Kaplan-Meier method will be used to estimate the distribution of PFS time.
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The time of registration to documentation of disease event where a disease event is local/regional/distant progression, contralateral breast disease, second primary disease or death due to any cause, assessed up to 3 months
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Response rate, defined as the proportion of patients whose tumor responds to treatment (Cohort II)
時間枠:Up to 3 months
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Calculated as the number of eligible patients whose tumor meets the criteria for a CR or PR on two consecutive evaluations at least 6 weeks apart divided by the number of eligible patients with metastatic breast cancer refractory to taxanes who begin treatment.
A 95% binomial confidence interval will be constructed for the true response rate.
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Up to 3 months
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Severity of all adverse events, graded according to NCI CTCAE v4.0
時間枠:Up to 3 months
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The severity of all adverse events (overall, by dose-level, and by tumor group) will be tabulated and summarized in this patient population.
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Up to 3 months
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Time until hematologic nadir for ANC
時間枠:Up to 3 months
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Up to 3 months
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Time until hematologic nadir for platelets
時間枠:Up to 3 months
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Up to 3 months
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Time until hematologic nadir for WBC
時間枠:Up to 3 months
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Up to 3 months
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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 |
---|---|---|
Incidence of toxicity, as assessed using PRO-CTCAE
時間枠:Up to 3 months
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The PRO-CTCAE will be summarized descriptively, and the dropout rate will be used for feasibility study.
Informal comparison and correlation of the PRO-CTCAE symptoms with their corresponding items in clinician reported CTCAE will be conducted in an exploratory manner.
Chi-squared tests will be used without adjustment for multiple comparisons.
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Up to 3 months
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その他の成果指標
結果測定 |
メジャーの説明 |
時間枠 |
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Pharmacokinetic (PK) parameters of cilengitide, including area under curve (AUC), maximum concentration Cmax and trough plasma concentrations
時間枠:Baseline; 1, 1.5, 2, 3, 4, and 5 hours post-cilengitide day 1 of courses 1 and 2; 27 hours post-paclitaxel day 2 of courses 1 and 2
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Analyses will be primarily descriptive in nature.
PK parameters will be determined from the individual plasma concentration-time curves of cilengitide, using non-compartmental and/or compartmental models.
These parameters will be correlated to clinical outcomes such as tumor response.
The possible effects of cilengitide upon paclitaxel pharmacokinetics, and vice-versa, will be explored using standard parametric or non-parametric techniques.
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Baseline; 1, 1.5, 2, 3, 4, and 5 hours post-cilengitide day 1 of courses 1 and 2; 27 hours post-paclitaxel day 2 of courses 1 and 2
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PK parameters of paclitaxel, including AUC, Cmax and trough plasma concentrations
時間枠:Baseline; 1, 1.5, 2, 3, 4, and 5 hours post-cilengitide day 1 of courses 1 and 2; 27 hours post-paclitaxel day 2 of courses 1 and 2
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Analyses will be primarily descriptive in nature.
PK parameters will be determined from the individual plasma concentration-time curves of paclitaxel, using non-compartmental and/or compartmental models.
These parameters will be correlated to clinical outcomes such as tumor response.
The possible effects of cilengitide upon paclitaxel pharmacokinetics, and vice-versa, will be explored using standard parametric or non-parametric techniques.
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Baseline; 1, 1.5, 2, 3, 4, and 5 hours post-cilengitide day 1 of courses 1 and 2; 27 hours post-paclitaxel day 2 of courses 1 and 2
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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
一次修了 (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
本研究に関する用語
追加の関連 MeSH 用語
その他の研究ID番号
- NCI-2013-00619 (レジストリ識別子:CTRP (Clinical Trial Reporting Program))
- P30CA015083 (米国 NIH グラント/契約)
- U01CA069912 (米国 NIH グラント/契約)
- MC0915 (その他の識別子:Mayo Clinic)
- 8335 (CTEP)
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。
IV期乳がんの臨床試験
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University of TartuTartu University Hospital; Estonian Science Foundation募集
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Mayo ClinicNational Cancer Institute (NCI)募集子宮頸部腺扁平上皮がん | 特に明記されていない子宮頸部扁平上皮癌 | 再発子宮頸がん | ステージ IB3 子宮頸がん FIGO 2018 | ステージ II 子宮頸がん FIGO 2018 | ステージ IIA 子宮頸がん FIGO 2018 | Stage IIA1 子宮頸がん FIGO 2018 | Stage IIA2 子宮頸がん FIGO 2018 | ステージ IIB 子宮頸がん FIGO 2018 | ステージ III 子宮頸がん FIGO 2018 | ステージ IIIA 子宮頸がん FIGO 2018 | Stage IIIB 子宮頸がん FIGO 2018 | ステージ IIIC 子宮頸がん FIGO 2018 | Stage... およびその他の条件アメリカ
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Central and North West London NHS Foundation TrustBritish HIV Association (BHIVA)まだ募集していませんHIV感染症 | B型肝炎
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Hvidovre University HospitalElsassFonden終了しました
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McGill University Health Centre/Research Institute...Northwestern University募集
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Nantes University Hospital完了
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Fundació Sant Joan de DéuStanley Medical Research Institute; Parc Sanitari Sant Joan de Déu; Hospital Sant Joan de Deu完了