Neu Direction: Testing the Efficacy of Adding HER Inhibition to Standard of Care in Metastatic MLH1-low Endocrine-resistant ER+/HER2- Breast Cancer
2026年7月22日 更新者：Asona Juwan Lui、University of California, San Diego
Neu Direction: A Single Center Phase II Randomized Clinical Trial to Assess the Efficacy of Adding HER Inhibition to Standard of Care in Patients With Metastatic MLH1-low Endocrine-resistant ER+/HER2- Breast Cancer
The goal of this clinical trial is to learn if neratinib, an FDA-approved oral pan-HER2/3/4 inhibitor, improves disease control for participants with metastatic endocrine-resistant ER+/HER2-negative breast cancer. Neratinib is already approved for the treatment of HER2-postive breast cancers. The study will also learn about the safety of adding this drug to standard of care treatments. The main questions it aims to answer are:
- Does adding neratinib to standard of care systemic therapy improve disease control for patients with metastatic hormone-driven breast cancer that is resistant to endocrine therapy?
- What side effects do participants have when adding neratinib to standard of care therapy? Researchers will compare standard of care endocrine therapy regimens with and without neratinib to see if neratinib improves control of treatment-resistant metastatic breast cancer that has continued to progress while eon first line endocrine therapy.
Participants will:
- Take standard of care endocrine therapy for metastatic endocrine-resistant breast cancer as determined by their medical oncologist or standard of care therapy with neratinib daily
- Visit the clinic every 3 months for checkups, tests and imaging studies
調査の概要
状態
まだ募集していません
詳細な説明
This is a prospective 2-arm Phase II study testing the efficacy of adding neratinib to standard of care therapy in patients with MLH1-low ER+/HER2- endocrine-resistant breast cancer .
Patients with endocrine-resistant ER+/HER2- breast cancer who have lesions visible on CT scan will be recruited as they are seen in breast medical oncology and radiation oncology clinics at UC San Diego Health.
Patients will be eligible if they have measurable persistent, recurrent, progressive or metastatic disease on imaging (including FDG PET scan) while on endocrine therapy.
At least one lesion must be biopsied and confirmed ER+ by immunohistochemistry and HER2- within 6 months of study screening.
Genomic mutation profile will be analyzed along with trial results to identify other potential mutations associated with MLH1 expression and/or neratinib response.
Participants will be stratified by nuclear MLH1 expression on their biopsy tissue using immunohistochemistry. MLH1negative (nuclear MLH1 detectable in <5% of tumor cells) and MLH1-low patients (<50% tumor cells positive) hereafter grouped as "MLH1-low" will be randomized to standard of care without (75 participants) or with (75 participants) the addition of neratinib in Arm 1 and Arm 2 respectively .
Standard of care therapy can include any endocrine therapy with or without CDK4/6 inhibitors.
Prior exposure to CDK4/6 inhibitors is acceptable but not prior HER2-targeted therapy.
Neratinib will be administered with a standard ramp up to therapeutic dose to minimize side effects with 120mg daily for 1 week, 160mg daily for 1 week and then 240mg daily thereafter.
Treatment response will be monitored via imaging every 3 months while on study and measured using RECIST v. 1.1 criteria and/or mPERCIST criteria as appropriate using FDG-PET.
Participants will remain on study until cessation due to side effects or disease progression.
Biopsy at disease progression will be encouraged but not required.
研究の種類
介入
入学 (推定)
150
段階
- フェーズ2
連絡先と場所
このセクションには、調査を実施する担当者の連絡先の詳細と、この調査が実施されている場所に関する情報が記載されています。
研究連絡先
- 名前：Asona Lui, MD, PhD
- 電話番号：858-822-4319
- メール：ajlui@health.ucsd.edu
研究連絡先のバックアップ
- 名前：Alyssa Beck, MD
- 電話番号：858-657-7000
- メール：a4beck@health.ucsd.edu
研究場所
-
-
California
-
La Jolla、California、アメリカ、92037
- UC San Diego Health Moores Cancer Center
-
コンタクト：
- Sauntee Braddock
- 電話番号：858-534-8248
- メール：sbraddock@health.ucsd.edu
-
主任研究者：
- Asona Lui, MD, PhD
-
副調査官：
- Alyssa Beck, MD
-
副調査官：
- Svasti Haricharan, PhD
-
-
参加基準
研究者は、適格基準と呼ばれる特定の説明に適合する人を探します。これらの基準のいくつかの例は、人の一般的な健康状態または以前の治療です。
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
いいえ
説明
Inclusion Criteria:
- Female over the age of 18 at the time of study enrollment
- Not pregnant, planning to become pregnant or breast feeding
- Metastatic ER+/HER2- breast cancer that has progressed on 1st line therapy including endocrine therapy +/- CDK4/6 inhibitors
- At least one metastatic lesion visible on imaging (including FDG-PET)
- At least one metastatic lesion must be biopsied and confirmed ER+ and HER2- by immunohistochemistry within 6 months of study screening (HER2 equivocal disease will be confirmed HER2- by FISH)
- Tumors must be MLH1-low defined by <50% tumor cells positive for nuclear MLH1 expression on immunohistochemistry
- Standard of care next line endocrine therapy can include any endocrine therapy
- Performance status ECOG > 3
- Life expectancy > 1 year
- Ability to get serial imaging studies
Exclusion Criteria:
- History of concurrent use of other HER2-targeted therapy
- Concurrent use of other targeted systemic therapy
- History of other cancers other than non-melanoma skin cancer
- Actionable mutations on tumor genomic sequencing will be ineligible, and those participants encouraged to proceed with the relevant targeted therapy
- Participants where there is not at least one imaging apparent lesion that has not been treated with prior targeted therapy (for example palliative radiation or cryoablation)
- Contraindications to Neratinib use including allergy or hypersensitivity
- Baseline grade 3+ diarrhea
研究計画
このセクションでは、研究がどのように設計され、研究が何を測定しているかなど、研究計画の詳細を提供します。
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：独身
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
Standard of Care 2nd or 3rd line endocrine therapy with or without CDK4/6 inhibitor
|
Endocrine therapy with out without CDK4/6 inhibitor
Endocrine therapy with or without CDK 4/6 inhibitor
|
|
実験的：Stanard of Care + Neratinib
Standard of Care 2nd or 3rd line endocrine therapy with or without CDK4/6 inhibitor + Neratinib
|
Endocrine therapy with or without CDK 4/6 inhibitor
Neratinib 120mg daily for 1 week, 160mg daily for 1 week and then 240mg daily thereafter
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 |
|---|---|---|
|
Median Progression-Free Survival
時間枠：From enrollment through study completion, an average of 1 year.
|
From enrollment through study completion, an average of 1 year.
|
|
|
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
時間枠：From enrollment through study completion, an average of 1 year.
|
Adverse events will be quantified using the CTCAE v4.0 every 3 months
|
From enrollment through study completion, an average of 1 year.
|
協力者と研究者
ここでは、この調査に関係する人々や組織を見つけることができます。
捜査官
- 主任研究者：Asona Lui, MD, PhD、UC San Diego
出版物と役立つリンク
研究に関する情報を入力する責任者は、自発的にこれらの出版物を提供します。これらは、研究に関連するあらゆるものに関するものである可能性があります。
一般刊行物
- Mazumder A, Dewitt J, Oropeza E, Punturi N, Lozano D, Raghunathan M, Piscitelli J, Sajjadi E, GueriniRocco E, Venetis K, Ivanova M, Mane E, Dercole M, Concardi A, Fusco N, Manhart C, Bainbridge M, Haricharan S. Aberrant cytoplasmic localization of MLH1 characterizes a cell population that seeds breast cancer recurrence. Nat Commun. 2025 Dec 10;17(1):564. doi: 10.1038/s41467-025-67257-8.
- Sajjadi E, Venetis K, Piciotti R, Invernizzi M, Guerini-Rocco E, Haricharan S, Fusco N. Mismatch repair-deficient hormone receptor-positive breast cancers: Biology and pathological characterization. Cancer Cell Int. 2021 May 17;21(1):266. doi: 10.1186/s12935-021-01976-y.
- Anurag M, Punturi N, Hoog J, Bainbridge MN, Ellis MJ, Haricharan S. Comprehensive Profiling of DNA Repair Defects in Breast Cancer Identifies a Novel Class of Endocrine Therapy Resistance Drivers. Clin Cancer Res. 2018 Oct 1;24(19):4887-4899. doi: 10.1158/1078-0432.CCR-17-3702. Epub 2018 May 23.
- Haricharan S, Punturi N, Singh P, Holloway KR, Anurag M, Schmelz J, Schmidt C, Lei JT, Suman V, Hunt K, Olson JA Jr, Hoog J, Li S, Huang S, Edwards DP, Kavuri SM, Bainbridge MN, Ma CX, Ellis MJ. Loss of MutL Disrupts CHK2-Dependent Cell-Cycle Control through CDK4/6 to Promote Intrinsic Endocrine Therapy Resistance in Primary Breast Cancer. Cancer Discov. 2017 Oct;7(10):1168-1183. doi: 10.1158/2159-8290.CD-16-1179. Epub 2017 Aug 11.
- Punturi NB, Seker S, Devarakonda V, Mazumder A, Kalra R, Chen CH, Li S, Primeau T, Ellis MJ, Kavuri SM, Haricharan S. Mismatch repair deficiency predicts response to HER2 blockade in HER2-negative breast cancer. Nat Commun. 2021 May 19;12(1):2940. doi: 10.1038/s41467-021-23271-0.
研究記録日
これらの日付は、ClinicalTrials.gov への研究記録と要約結果の提出の進捗状況を追跡します。研究記録と報告された結果は、国立医学図書館 (NLM) によって審査され、公開 Web サイトに掲載される前に、特定の品質管理基準を満たしていることが確認されます。
主要日程の研究
研究開始 (推定)
2027年7月1日
一次修了 (推定)
2032年5月1日
研究の完了 (推定)
2035年6月1日
試験登録日
最初に提出
2026年7月14日
QC基準を満たした最初の提出物
2026年7月22日
最初の投稿 (実際)
2026年7月27日
学習記録の更新
投稿された最後の更新 (実際)
2026年7月27日
QC基準を満たした最後の更新が送信されました
2026年7月22日
最終確認日
2026年7月1日
詳しくは
本研究に関する用語
キーワード
追加の関連 MeSH 用語
その他の研究ID番号
- BC250474 (その他の助成金/資金番号：Congressionally Designated Medical Research Program (CDMRP), US ARMY MEDICAL RESEARCH ACQUISITION ACTIVITY)
- 813310 (その他の識別子：UC San Diego Institutional Review Board (IRB))
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?
はい
IPD プランの説明
Only IPD used in the results publication
IPD 共有時間枠
Beginning 6 months and ending 3 years after publication of results
IPD 共有アクセス基準
Proposal that describes planned analyses must be submitted and approved by the Principle Investigator, Asona Lui and data sharing agreement must be signed with the requesters institution.
Evidence of IRB approval must be provided by the requestor prior to the sharing of any data.
IPD 共有サポート情報タイプ
- STUDY_PROTOCOL
- SAP
- ICF
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
はい
米国FDA規制機器製品の研究
いいえ
米国で製造され、米国から輸出された製品。
いいえ
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。