A Vaccine (STEMVAC) for Improving Survival in Patients With Triple-Negative Breast Cancer and Moderate or Extensive Residual Cancer Burden
A Multiantigen Vaccine (STEMVAC) for Adjuvant Treatment of Patients With Moderate or Extensive Residual Triple-Negative Breast Cancer
調査の概要
状態
詳細な説明
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM A: Patients receive CD105/Yb-1/SOX2/CDH3/MDM2-polyepitope plasmid deoxyribonucleic acid (DNA) vaccine (STEMVAC) with recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF) intradermally (ID) every 3 weeks for 3 doses. Patients then receive booster vaccines ID 9 weeks after vaccine 3 and 18 weeks after booster 1. Patients also undergo collection of blood samples throughout the trial.
ARM B: Patients receive GM-CSF ID every 3 weeks for 3 doses. Patients then receive booster vaccines ID 9 weeks after vaccine 3 and 18 weeks after booster 1. Patients also undergo collection of blood samples throughout the trial.
After completion of study treatment, patients are followed up at 3 weeks after their last vaccination and then every 6 months for 3 years.
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:Research Coordinator(s)
- 電話番号:866-932-8588
- メール:cvitrial@uw.edu
研究場所
-
-
Washington
-
Seattle、Washington、アメリカ、98109
- Fred Hutch/University of Washington Cancer Consortium
-
主任研究者:
- Natasha Hunter, MD
-
コンタクト:
- Research Coordinator(s)
- 電話番号:866-932-8588
- メール:cvitrial@uw.edu
-
-
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:
- At least 18 years of age
- Eastern Cooperative Oncology Group (ECOG) performance status score of ≤ 2
- Triple-negative breast cancer as determined by the treating oncologist
- Completed standard of care neoadjuvant chemotherapy in the opinion of their treating oncologist
- Patients whose tumors progress on neoadjuvant therapy may be enrolled
- No clinical evidence of local or distant recurrence
- Plan to receive standard of care adjuvant directed therapy
- Completed standard of care locoregional treatment, including definitive breast and lymph node surgery followed by standard radiation therapy, if recommended
- Residual cancer burden (RCB) index 2 or 3 as calculated per routine anatomic pathology clinical standards
- Absolute neutrophil count (ANC) ≥ 800/μL (within 30 days of first study vaccine administration)
- Hemoglobin (Hgb) ≥ 8 g/dL (within 30 days of first study vaccine administration)
- Platelets ≥ 75,000/ μL (within 30 days of first study vaccine administration)
- Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN), except patients with Gilbert's syndrome, in whom total bilirubin must be < 3.0 mg/dL (within 30 days of first study vaccine administration)
- Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ≤ 1.5 x institutional ULN (within 30 days of first study vaccine administration)
- Creatinine ≤ 1.5 x ULN mg/dL or creatinine clearance > 60 mL/min (within 30 days of first study vaccine administration)
At least 28 days post systemic steroids prior to enrollment, unless used as part of prophylaxis to prevent intravenous (IV) contrast reactions.
- Topical, ocular, intra-articular, intranasal, inhalational corticosteroids (with minimal systemic absorption) are allowed
- Must have recovered from major infections and/or surgical procedures; and in the opinion of the investigator, not have any significant active concurrent medical illnesses or condition precluding protocol treatment
- Patients of child-bearing potential must agree to use dual methods of contraception and have a negative urine pregnancy test at screening, and male patients must use an effective barrier method of contraception if sexually active with a person of child-bearing potential. Acceptable methods of contraception are abstinence, condoms with contraceptive foam, oral, implantable or injectable contraceptives, contraceptive patch, intrauterine device, diaphragm with spermicidal gel, or a sexual partner who is surgically sterilized or post-menopausal
Exclusion Criteria:
- Toxicities related to prior exposure to immune checkpoint inhibitors for which immune checkpoint inhibitors cannot be safely continued as determined by study investigator
Germline BRCA1 or BRCA2 mutations with adjuvant olaparib planned within the study period
- NOTE: If olaparib is not planned, then these patients are eligible
Any known cardiac conditions:
- Symptomatic restrictive cardiomyopathy
- Dilated cardiomyopathy
- Unstable angina within 4 months prior to enrollment
- New York Heart Association functional class III-IV heart failure on active treatment
- Symptomatic pericardial effusion
- Autoimmune disease requiring active systemic treatment
- Known hypersensitivity reaction to the GM-CSF adjuvant; any known contra-indication to GM-CSF
- Pregnant or breast feeding
- Known history of human immunodeficiency virus (HIV) infection, hepatitis B (e.g., hepatitis B virus surface antigen [HBsAg] reactive), or hepatitis C (e.g., hepatitis C virus [HCV] ribonucleic acid [RNA] is detected)
- Major surgery within the 4 weeks prior to initiation of first study vaccine
- Enrollment in any other clinical protocol or investigational trial that involves concurrent administration of experimental therapy and/or therapeutic devices, or investigational drug. Patients who completed prior clinical trials (such as neoadjuvant treatment, surgery or radiation trials) and are on long term follow up are permitted
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 |
|---|---|
|
実験的:Arm A (STEMVAC, GM-CSF)
Patients receive STEMVAC with GM-CSF ID every 3 weeks for 3 doses.
Patients then receive booster vaccines ID 9 weeks after vaccine 3 and 18 weeks after booster 1. Patients also undergo collection of blood samples throughout the trial.
|
血液サンプルの採取を受ける
他の名前:
指定された ID
他の名前:
Given ID
他の名前:
|
|
アクティブコンパレータ:Arm B (GM-CSF)
Patients receive GM-CSF ID every 3 weeks for 3 doses.
Patients then receive booster vaccines ID 9 weeks after vaccine 3 and 18 weeks after booster 1. Patients also undergo collection of blood samples throughout the trial.
|
血液サンプルの採取を受ける
他の名前:
Given ID
他の名前:
|
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 |
|---|---|---|
|
Invasive breast cancer free survival (IBCFS)
時間枠:Time from randomization to local or distant recurrence or death, assessed up to 3 years
|
Kaplan-Meier curves will be generated with median estimation and 95% confidence interval, and log-rank tests will be conducted to compare the survival difference between groups.
Will calculate the 3-year IBCFS rate with a 95% confidence interval from Kaplan-Meier methods using Greenwood standard errors.
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Time from randomization to local or distant recurrence or death, assessed up to 3 years
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|
Dynamics and characteristics of circulating tumor deoxyribonucleic acid (ctDNA)
時間枠:Up to 3 weeks after last vaccination
|
Through serial ctDNA evaluation, each sample will be assessed for ctDNA detectability and, if detectable, total ctDNA mass (continuous variable, as reported by the assay platform) will be calculated.
ctDNA detectability and quantitative ctDNA measures will be summarized descriptively by timepoint and study arm, and changes over time will be evaluated using methods appropriate to the final endpoint definition, data distribution, and repeated-measures structure of the data.
Associations with IBCFS will also be explored.
Copy number variants (including aneuploidy, chromosome-level gains, losses, and amplifications, as defined by the final assay methodology) will also be tracked and tabulated, and changes over time will be evaluated descriptively in both study arms.
|
Up to 3 weeks after last vaccination
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Incidence of adverse events
時間枠:Up to 3 weeks after last vaccination
|
Safety and systemic toxicity will be determined by clinical and laboratory parameters evaluated at protocol-specified time points.
Toxicity will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 6.0.
The type and grade of toxicities observed during the immunization regimen will be summarized, and the duration of toxicities will be summarized using descriptive statistics.
All adverse events reported by the investigator will be tabulated according to the affected body system.
The frequency and severity of adverse events will be summarized using proportions and corresponding 95% confidence intervals.
Demographic and baseline characteristics obtained at enrollment will be summarized in tabular and/or graphical formats using descriptive statistics.
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Up to 3 weeks after last vaccination
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Immune response
時間枠:Up to 3 weeks after last vaccination
|
Immune response to CD105/Yb-1/SOX2/CDH3/MDM2-polyepitope plasmid DNA vaccine (STEMVAC) will be measured in peripheral blood functionally by IFN-g enzyme-linked immunosorbent spot, phenotypically using cytometry by time-of-flight to identify T-cell clonal populations, and genomically, using T-cell receptor beta sequencing of CD4+ CD8+ T-cells.
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Up to 3 weeks after last vaccination
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Expression of epithelial to mesenchymal transformation (EMT)-associated genes
時間枠:Archival tissue is collected after enrollment, within 30 days of baseline visit
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EMT-associated gene expression profiles in residual triple negative breast cancer in surgical pathology samples will be defined for each patient with particular attention on STEMVAC antigen expression.
Expression of these EMT-related genes will be assessed using RNA extracted from formalin-fixed paraffin-embedded tissue.
|
Archival tissue is collected after enrollment, within 30 days of baseline visit
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協力者と研究者
スポンサー
捜査官
- 主任研究者:Natasha Hunter, MD、Fred Hutch/University of Washington Cancer Consortium
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
- RG1126489
- NCI-2026-04722 (レジストリ識別子:CTRP (Clinical Trial Reporting Program))
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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