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トラスツズマブ デルクステカン + 定位放射線治療（SRS）によるHER2陽性乳がん脳転移の治療

2026年9月29日 更新者：Baptist Health South Florida

HER-2陽性乳がんによる脳転移患者を対象としたトラスツズマブ デルクステカンと定位放射線治療(SRS)併用の第1相臨床試験

A phase I clinical trial (a type of research study) for people with human epidermal growth factor receptor 2 (HER-2) positive breast cancer with metastasis to the brain. This research study will evaluate how well brain metastases can be controlled using a type of radiation therapy known as stereotactic radiosurgery (SRS) when combined with the therapeutic agent Trastuzumab Deruxtecan (T-DXd). The combined use of SRS with T-DXd is considered investigational.

調査の概要

状態

まだ募集していません

条件

介入・治療

研究の種類

介入

入学 (推定)

20

段階

  • フェーズ 1

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

研究連絡先のバックアップ

研究場所

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

18年歳以上 (大人、高齢者)

健康ボランティアの受け入れ

いいえ

受講資格のある性別

女性

説明

Inclusion Criteria:

  1. Histologically confirmed HER-2-positive breast cancer with newly diagnosed brain metastases.
  2. ECOG Performance Status (PS) of 0, 1, 2.
  3. Participants with 1-10 brain metastases will be candidates for T-DXd with SRS at the discretion of the treating radiation oncologist. Intra-cranial metastasis must measure 3 cm or less in the greatest dimension.
  4. Age ≥ 18 years
  5. Signed written informed consent by patient or legally authorized representative. A signed informed consent must be obtained prior to any study-specific procedures.
  6. Life expectancy of at least 12 weeks.
  7. Any number of prior systemic therapies will be allowed, except T-DXd.
  8. Hemoglobin ≥ 9 g/dL, White blood count ≥ 3.0 × 109/L, Absolute Neutrophil count ≥ 1.5 × 109/L and platelet count ≥ 100 × 109/L.
  9. Serum bilirubin ≤ 1.5 × upper limit of normal (ULN).
  10. AST and/or ALT ≤ 2 × ULN (≤ 5 × ULN when clearly attributable to the presence of liver metastases).
  11. Serum creatinine ≤ 1.5 × ULN or calculated creatinine clearance > 60 mL/min.
  12. Ability to comply with study procedures and monitoring.
  13. For individuals of childbearing potential, a negative pregnancy test should be obtained within 7 days prior to the start of therapy.
  14. Participants must have left ventricular ejection fraction (LVEF) ≥ 50% by either an echocardiogram (ECHO) or multi-gated acquisition (MUGA) scan within 28 days before enrollment (to be assessed as clinically indicated).
  15. Male or female participants of reproductive potential need to employ two highly effective and acceptable forms of contraception throughout their participation in the study and for 7 months after last dose of T-DXd.

Highly effective and acceptable forms of contraception are:

  • Male condom plus spermicide
  • Cap plus spermicide
  • Diaphragm plus spermicide
  • Copper T
  • Progesterone T
  • Levonorgestrel-releasing intrauterine system (e.g., Mirena®)
  • Implants
  • Hormone shot or injection
  • Combined pill
  • Mini-pill
  • Patch

Postmenopausal individuals on the study (that will not need contraception) is defined as:

  • Amenorrhoeic for 1 year or more following cessation of exogenous hormonal treatments.
  • LH and FSH levels in the postmenopausal range for individuals < 50 years.
  • Radiation-induced oophorectomy with last menses > 1 year ago.
  • Chemotherapy-induced menopause with > 1 year interval since last menses.
  • Surgical sterilization (bilateral oophorectomy or hysterectomy).

Men and women and members of all races and ethnic groups are eligible for this trial.

Exclusion Criteria:

  1. Participants with leptomeningeal metastases documented by MRI or CSF evaluation.
  2. Evidence of intra-tumoral or peri-tumoral hemorrhage deemed clinically significant by the treating physician.
  3. Brain metastases within 5 mm of the optic chiasm or optic nerve.
  4. Significant or recent acute gastrointestinal disorders with diarrhea as a major symptom, e.g., Crohn's disease, malabsorption, or CTCAE grade > 2 diarrhea of any etiology at baseline.
  5. History of clinically significant or uncontrolled cardiac disease, including congestive heart failure, angina, myocardial infarction, arrhythmia, New York Heart Association (NYHA) functional classification of 3 or 4.
  6. Unable to undergo brain MRI.
  7. Screen for human immunodeficiency virus (HIV) infection or chronic Hepatitis B or C. HIV/HBV/HCV testing per institutional practice.
  8. All toxicities from prior therapies must have resolved to CTCAE v5.0 grade 1 or better by the time of study enrollment.
  9. Other concurrent severe and/or uncontrolled concomitant medical conditions (e.g., active, or uncontrolled infection, uncontrolled diabetes, second active malignancy) that could cause unacceptable safety risks or compromise compliance with the protocol.
  10. Currently receiving other investigational cancer therapy (with the exception of continuing therapy with GnRH analogues) within 4 weeks prior to start of study treatment.
  11. Mean QT interval corrected heart rate (QTc) ≥ 470 ms calculated from 3 electrocardiograms using Fredericia's Correction, calculated as: 8.22 ∛(RR interval)
  12. LVEF <50%.
  13. Ineligible for treatment with T-DXd.
  14. Ineligible for treatment with SRS.
  15. Active or prior documented ILD/pneumonitis or suspected ILD/pneumonitis that cannot be ruled out by imaging at screening.
  16. History of hypersensitivity to T-DXd.
  17. History and/or confirmed corneal ulceration.
  18. Pregnant or breast feeding. The patients should not breast feed for 7 months after stopping the drug.
  19. Use of anthracyclines will be prohibited while on the protocol.
  20. Prior cranial radiation is not allowed.

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：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
実験的：T-DXd + SRS

All participants will receive SRS and the drug T-DXd. The goal is to evaluate safety and determine an appropriate dose.
薬：Trastuzumab Deruxtecan

T-DXd will be given as an IV infusion every 21 days. This Phase 1 study will use predefined dose levels (5.4 mg/kg, 4.4 mg/kg, and 3.2 mg/kg) to evaluate safety and tolerability. Participants may continue treatment until disease progression, unacceptable side effects, or withdrawal.

他の名前：
  • T-DXd
放射線：Stereotactic Radiosurgery

Participants will receive SRS to intact brain metastases. Typical dosing is 20-24 Gy in a single fraction for lesions <20 mm, or 27 Gy in 3 fractions for lesions ≥20 mm. Exact dosing will be based on the treating radiation oncologist's clinical judgment.

他の名前：
  • SRS

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
Incidence of dose-limiting toxicities (DLTs)
時間枠：3 weeks

DLTs will be assessed using Common Terminology Criteria for Adverse Events (CTCAE) v5.0 starting from the first dose of T-DXd through 3 weeks after SRS. DLT is defined as the appearance of side effects during treatment that are severe enough to prevent continuation of treatment at a participant's assigned dose. Any of the following events will be considered a DLT if treatment-related:

  • ≥ Grade 4 non-hematologic toxicity except nausea and vomiting (if manageable with supportive care measures), alopecia, drug-related fever, and toxicities secondary to neutropenia and sepsis
  • ≥ Grade 3 neurologic toxicity (sensory or autonomic)
  • Grade 4 platelet count (<25,000/mm³) 50 days beyond the start of the most recent chemotherapy (not related to recurrent leukemia)
  • Grade 4 neutropenia 50 days beyond the start of the most recent chemotherapy (not related to recurrent leukemia)
  • Grade 3 non-hematologic toxicity (excluding alopecia or toxicities secondary to neutropenia
3 weeks
Determination of the maximum tolerated dose (MTD) of T-DXd in combination with SRS
時間枠：3 weeks

The MTD will be determined using a standard 3+3 dose de-escalation design across predefined dose levels of T-DXd (5.4 mg/kg, 4.4 mg/kg, and 3.2 mg/kg IV every 21 days), based on the number of participants who experience a DLT at each dose level.
3 weeks

二次結果の測定

結果測定
メジャーの説明
時間枠
Intracranial Progression-free survival (PFS) at 6 months (PFS-6)
時間枠：6 months

Intracranial PFS-6 will be defined as the time from first dose of study drug until intracranial disease progression (i.e., progression within the skull) or death from any cause using Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) at 6 months post-treatment. Progression is defined as at least 20% increase in the sum of the longest diameters of the target lesions, appearance of any new lesions, or unequivocable progression of any non-target lesions. For participants whose disease has not progressed at the time of the analysis, censoring will be performed using the date of the last valid disease assessment.
6 months
Extracranial PFS-6
時間枠：6 months

Extracranial PFS-6 will be defined as the time from first dose of study drug until extracranial disease progression (i.e., progression outside of the skull) or death from any cause using Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) at 6 months post-treatment. Progression is defined as at least 20% increase in the sum of the longest diameters (LD) of the target lesions compared to the smallest recorded LD since treatment started, appearance of any new lesions, or unequivocable progression of any non-target lesions. For participants whose disease has not progressed at the time of the analysis, censoring will be performed using the date of the last valid disease assessment.
6 months
Overall survival (OS)
時間枠：2 years

Median OS will be defined as the time from the beginning of study drug treatment until death due to any cause at the end of the study (~2 years). For participants who have not died at the time of the analysis, censoring will be performed using the date the participant was last known to be alive.
2 years
Objective response rate (ORR)
時間枠：2 years

ORR will be defined as the proportion of participants achieving a complete response (CR) or partial response (PR) using RECIST v1.1 as their best overall response by the end of the study (~2 years). Participants with CR or PR will be counted as successes and all other participants (including those with missing response information) will be counted as failures. CR is defined as disappearance of all target and non-target lesions, determined by two separate observations conducted not less than 4 weeks apart. There can be no appearance of new lesions. All lymph nodes must be non-pathological in size (<10 mm short axis). PR is defined as at least 30% decrease in the sum of the LD of target lesions compared to baseline. There can be no appearance of new lesions.
2 years
Intracranial PFS-6 comparison to historical data
時間枠：6 months

Intracranial PFS-6 as defined in Outcome 3 will be compared to historical data.
6 months
Extracranial PFS-6 comparison to historical data
時間枠：6 months

Extracranial PFS-6 as defined in Outcome 4 will be compared to historical data.
6 months
OS comparison to historical data
時間枠：2 years

Median OS as defined in Outcome 5 will be compared to historical data.
2 years
ORR comparison to historical data
時間枠：2 years

ORR as defined in Outcome 6 will be compared to historical data.
2 years

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。

スポンサー

Baptist Health South Florida

協力者

National Brain Tumor Society

捜査官

  • 主任研究者：Manmeet Ahluwalia、Baptist Health Herbert Wertheim Cancer Institute

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。

便利なリンク

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1月1日

一次修了 (推定)

2029年2月1日

研究の完了 (推定)

2030年2月1日

試験登録日

最初に提出

2026年2月16日

QC基準を満たした最初の提出物

2026年3月2日

最初の投稿 (実際)

2026年3月6日

学習記録の更新

投稿された最後の更新 (実際)

2026年10月1日

QC基準を満たした最後の更新が送信されました

2026年9月29日

最終確認日

2026年9月1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

  • 2025-AHL-001

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

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。

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