Targeting Immune Modulation in High Grade Serous Carcinoma: Combined Effects of Chemotherapy and Atorvastatin
The goal of this clinical trial is to learn how atorvastatin in patients with advanced high grade serous cancer of the ovary, fallopian tube, or peritoneum changes the tumor immune environment. The main question it aims to answer is:
- Does atorvastatin combined with standard of care chemotherapy and surgery changes the number of tumor-promoting macrophages in the tumor microenvironment
- Researchers will compare standard of care chemotherapy and surgery to see if there is a difference in tumor promoting macrophages.
- Participants will take atorvastatin (daily pill) alongside their standard treatment.
調査の概要
状態
研究の種類
入学 (推定)
段階
- フェーズ2
連絡先と場所
研究場所
-
-
Colorado
-
Aurora、Colorado、アメリカ、80045
- University of Colorado Anschutz
-
-
参加基準
適格基準
就学可能な年齢
- 大人
- 高齢者
健康ボランティアの受け入れ
説明
Inclusion Criteria:
- Be a patient with ovarian cancer aged 18-89
- Diagnosed via tissue biopsy not ascites
- For persons of reproductive potential, use of highly effective method(s) of contraception.
- Patients with primary Stage III/IV high-grade serous ovarian/fallopian tube/primary peritoneal cancer not amenable to upfront cytoreductive surgery.
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1 or 2.
- Absolute Neutrophil Count 1500 cells/mL
- Platelet count > 100,000 mL.
- Hemoglobin 9.0 g/dL
- Serum albumin ³ 2.5 g/dL.
- Total bilirubin ≤ 1.5 x upper limit of normal (ULN).
- aspartate aminotransferase (AST )and alanine aminotransferase (ALT) ≤ 3.0 x ULN.
- Serum creatinine ≤ 1.5x ULN
Exclusion Criteria:
- Inability to comply with study and follow-up procedures.
- Significant cardiovascular disease, such as New York Heart Association cardiac disease (class II or greater), myocardial infarction within the past 3 months, unstable arrhythmia, or unstable angina.
- Known clinically significant liver disease defined as AST and ALT > 3.0 x ULN and/or total bilirubin ≥ 1.5 x ULN, or documented history of active viral, alcoholic, or other hepatitis, cirrhosis, and inherited liver disease.
- Participation in investigational clinical trial within last 30 days.
Medical history of untreated HIV infection. Patients with medical history of HIV infection are eligible provided they meet following criteria
- Are stable on antiretroviral therapy for ≥4 weeks before randomization
- Agree to adhere to antiretroviral therapy per World Health Organization (WHO) guidelines
- Have no documented multi-drug resistance that would prevent effective antiretroviral therapy
- Have a viral load of <400 copies per mL at screening
- Have CD4+ T cell count at ≥ 350 cells per μL
- Have no history of acquired immunodeficiency syndrome (AIDS) -defining opportunistic infection ≤ 12 months before randomization.
- Inability to provide informed consent.
- Known central nervous system (CNS) malignancy or CNS metastases.
- Patients with previous malignancy within the past 2 years from cycle 1, day 1, except those with negligible risk of metastasis or death, such as adequately controlled basal cell carcinoma or squamous cell carcinoma of the skin or carcinoma in situ of the breast.
- History of stroke or transient ischemic attack (TIA) within 3 months prior to cycle 1 day 1(C1D1).
- Patients with prognosis for survival less than 6 months.
- Patients deemed otherwise clinically unfit for clinical trial per Investigator's discretion.
Patients with duodenal stent or other gastrointestinal (GI) disorder/defect that would interfere with absorption of oral medication.
o Includes patients unable to swallow orally administered medication and patients with GI disorders likely to interfere with absorption of the study medication
- Female patients who maintain fertility potential and refuse to comply to use contraception and be followed for pregnancy by pregnancy testing.
- Patients who are currently pregnant or lactating.
- Prior or current statin use that would prohibit randomization into SOC arm.
- Planned treatment with bevacizumab in the primary treatment setting.
- Diagnosis based on ascites assessment only and not a tissue biopsy.
- Patients deemed otherwise clinically unfit for clinical trial per investigators discretion
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:Standard of Care
neoadjuvant chemotherapy with 3-4 cycles of carboplatin/paclitaxel, interval debulking surgery, then 2-3 additional cycles of chemotherapy with carboplatin/paclitaxel
|
neoadjuvant chemotherapy with 3-4 cycles of carboplatin/paclitaxel, interval debulking surgery, then 2-3 additional cycles of chemotherapy with carboplatin/paclitaxel
|
|
実験的:Atorvastatin with Standard of Care
Patients in this arm will take atorvastatin daily alongside neoadjuvant chemotherapy with 3-4 cycles of carboplatin/paclitaxel, interval debulking surgery, then 2-3 additional cycles of chemotherapy with carboplatin/paclitaxel
|
Neoadjuvant chemotherapy with carboplatin and paclitaxel in addition to daily atorvastatin, interval debulking surgery, then 2-3 additional cycles of carboplatin and paclitaxel
|
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 |
|---|---|---|
|
Change from baseline of CD163+ tumor associated macrophages in post-treatment specimens.
時間枠:3 months
|
The primary efficacy endpoint is the change from baseline to the post-treatment surgical specimen in the mean CD163 H-score among CD68-positive tumor-associated macrophages.
CD68 and CD163 expression will be assessed by multispectral immunohistochemistry in paired pre-treatment biopsy and post-treatment surgical samples.
|
3 months
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Progression free survival
時間枠:5 years
|
Investigator-assessed progression-free survival will be defined as the time from randomization to the first documented occurrence of objective disease progression or death from any cause, whichever occurs first.
|
5 years
|
|
Overall Survival
時間枠:5 years
|
Overall survival as defined by the time of randomization to time of death from any cause.
|
5 years
|
協力者と研究者
捜査官
- 主任研究者:Nicole Marjon, MD, PhD、CU Anschutz
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
追加の関連 MeSH 用語
その他の研究ID番号
- 26-0543
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
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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