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Not yet recruitingPhase 1

Trastuzumab Deruxtecan + Stereotactic Radiosurgery (SRS) in HER2+ Breast Cancer Brain Metastases

Phase 1 Trial of Trastuzumab Deruxtecan With Stereotactic Radiosurgery (SRS) in Participants With Brain Metastases From HER-2 Positive Breast Cancer

Who can join

As published by the study on ClinicalTrials.gov. "Not stated" means the study hasn't said — ask the study team.

Age
18 Years and older
Sex
Female only
Healthy volunteers
Not accepted
Compensation
Not stated

Other requirements are listed under Eligibility below. Only the study team can confirm whether you can join.

What to expect

No one can promise a trial will help you personally — that is what the research is trying to find out.

What participation involves

Not stated in the study description — ask the study team about visits and procedures.

Compensation
Not stated
  • Study-related exams and procedures are typically provided at no cost. This is how many trials work in general — confirm the details for this study with the study team.
  • Participants are monitored closely by the research team throughout the study.
  • Some participants may receive access to an investigational treatment, which is still being studied.
  • Your participation helps researchers learn whether this approach could help future patients.

About this study

In plain language

This phase 1 study tests focused brain radiation, called SRS, with the drug trastuzumab deruxtecan (T-DXd). It is for adults with HER2-positive breast cancer that has newly spread to the brain. The study will see how well this experimental combination controls cancer in the brain.

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.

Compensation is read from the study's own description and may be missing — always confirm with the study team.

Eligibility

Who can join

  • Age 18 or older, with HER2-positive breast cancer confirmed by a tissue test and newly found cancer spread to the brain.
  • Have 1–10 brain tumors, each no larger than 3 cm. The radiation doctor must approve SRS treatment.
  • Be able to do all or most self-care, even if unable to work (ECOG score 0–2), and be expected to live at least 12 weeks.
  • May have had any number of past drug treatments for cancer, but not T-DXd.
  • Meet study blood count, liver, and kidney test limits. A heart scan must show a pumping level of at least 50% within 28 days before joining.
  • You or your legal representative must sign a consent form before study procedures. You must be able to follow study visits and testing.
  • If you could become pregnant, have a negative pregnancy test within 7 days before treatment starts.
  • If you could have or father a child, use two approved, highly effective birth control methods during the study and for 7 months after the last T-DXd dose.

Who can't join

  • Cancer in the layers covering the brain or spinal cord; serious bleeding in or around a tumor; or a brain tumor within 5 mm of nerves that carry vision signals.
  • Past radiation to the head, inability to have a brain MRI, or inability to receive SRS or T-DXd.
  • Serious or uncontrolled heart disease, a heart pumping level below 50%, or a prolonged heart rhythm measurement called QTc of at least 470 milliseconds.
  • Current, past, or suspected lung inflammation called ILD or pneumonitis; a past allergic reaction to T-DXd; or a history of an open sore on the clear front of the eye.
  • Serious or recent gut problems with diarrhea, or side effects from past treatment that have not improved to mild or better.
  • Other severe or uncontrolled health problems that could make treatment unsafe or prevent study participation, such as infection, diabetes, or another active cancer. The listing also includes screening for HIV and long-term hepatitis B or C.
  • Other experimental cancer treatment within 4 weeks before study treatment, except continued GnRH hormone therapy. Anthracycline cancer drugs cannot be used during the study.
  • Pregnant or breastfeeding. Breastfeeding is also not allowed for 7 months after stopping T-DXd.

Simplified for readability. The official criteria below are what the study team uses.

Official eligibility criteria

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.

Study sites (1)

FL