T-DM1 Alone Versus T-DM1 and Metronomic Temozolomide in Secondary Prevention of HER2-Positive Breast Cancer Brain Metastases Following Stereotactic Radiosurgery
TerminatedPhase 1, PHASE2Results postedLast updated 11 October 2023
What this trial tests
Phase 1, PHASE2 trial testing T-DM1 in Breast Cancer in 12 participants. Terminated before completion.
18 and older, any sex, with Breast Cancer or Brain Metastasis. Patients with the condition only — healthy volunteers not accepted.
Results — posted to ClinicalTrials.gov
Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.
Phase I: Maximum Tolerated Dose (MTD) of Temozolomide (TMZ) When Used With T-DM1 (Ado-trastuzumab)Primary· first 21 days of treatment
Maximum tolerated dose of TMZ when used in combination with T-DM1. MTD is defined as the dose level at which 0 or 1 participant in 6 has a dose limiting toxicity (DLT). A DLT is defined as grade 3 or higher non-hematologic adverse events excluding grade 3 hypertension controlled with anti-hypertensive therapy; or grade 3 asymptomatic electrolytes imbalance; grade 3 endocrinopathy; grade 3 asymptomatic increase in aspartate aminotransferase or alanine aminotransferase; and transient (lasting less than \<48 hours) nausea, emesis, or diarrhea if corrected with conservative measures within 24-48 h
Group
Value
95% CI
All Participants
40
Phase I: Number of Participants With Grade 3 and/or Grade 4 Adverse EventsSecondary· Evaluated at the beginning of every cycle while on study, for an average of 9.6 months (range 2.8-33.9 months).
Adverse events were assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0). Grade 3 is severe. Grade 4 is life-threatening.
Phase I: Number of Participants With Dose Limiting Toxicity (DLTs) at Each Dose LevelSecondary· After first cycle of treatment, up to 30 days
Number of participants with DLTs at each dose level 30 days after treatment. A DLT is defined as grade 3 or higher non-hematologic adverse events excluding grade 3 hypertension controlled with anti-hypertensive therapy; or grade 3 asymptomatic electrolytes imbalance; grade 3 endocrinopathy; grade 3 asymptomatic increase in aspartate aminotransferase or alanine aminotransferase; and transient (lasting less than \<48 hours) nausea, emesis, or diarrhea if corrected with conservative measures within 24-48 hours. A hematologic grade 4 neutropenia of ≥ 7 days duration, grade ≥ 3 thrombocytopenia, an
Phase I: Median SurvivalSecondary· From date of first therapy until death, an average of 40.79 months
Median amount of time participants survives after therapy. Survival compared between the two arms and Kaplan-Meier curves constructed with a two-tailed log-rank test used to compare the arms.
Phase I: Standard Time to Progression (TTP)Secondary· From first day of treatment to the day of disease progression, an average of 15 months.
TTP is the time between the first day of treatment to the day of disease progression. Progression was assessed using the Response Evaluation Criteria in Solid Tumors (RECIST). Progression is at least a 25% increase in the sum of products of all measurable lesions over smallest sum observed, clear worsening of any evaluable disease, appearance of any new lesion/site, or failure to return for evaluation due to death or deteriorating condition.
Phase I: Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0)Secondary· Date treatment consent signed to date off study, approximately 44 months and 27 days for level 1, 28 months and 10 days for level 2, and 40 months and 8 days for level 3.
Here is the number of participants with serious and/or non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent
Time frame: Date treatment consent signed to date off study, approximately 44 months and 27 days for level 1, 28 months and 10 days for level 2, and 40 months and 8 days for level 3..
Reporting threshold: 0%.
Adverse-event reports describe events observed during the trial — not all are caused by the drug.
Background:
Sometimes breast cancer spreads (metastasizes) to the brain. Researchers want to study new treatments for brain metastases. The drug Temozolomide is approved to treat brain tumors. Researchers want to see if combining it with the drug trastuzumab emtansine (T-DMI) prevents the formation of new metastases in the brain.
Objective:
To study if Temozolomide with T-DM1 lowers the chance of having new metastases in the brain.
Eligibility:
Adults at least 18 years old with a human epidermal growth factor receptor 2 (HER2)-positive breast cancer that has spread to the brain and was recently treated with stereotactic radiation or surgery.
Design:
Participants will be screened with
* Medical history
* Physical exam
* Heart tests
* A scan (computed tomography (CT) that makes a picture of the body using a small amount of radiation
* A scan (magnetic resonance imaging (MRI) that uses a magnetic field to make an image of the brain
* Blood tests.
* Pregnancy test.
The study will be done in 3-week cycles.
All participants will get T-DM1 on Day 1 of every cycle through a small plastic tube inserted in an arm vein.
Some participants will also take Temozolomide capsules by mouth every day.
Participants will keep a medication diary.
During the study, participants will also:
* Repeat most of the screening tests.
* Answer questions about their general well-being and functioning.
Participants will have lumbar puncture at least 2 times. A needle is inserted into the spinal canal low in the back and cerebrospinal fluid is collected. This will be done with local anesthesia and with the help of images.
Participants will be asked to provide tumor samples when available.
Participants will have a follow-up visit about 1 month after stopping the study drug. They will be contacted by telephone or email every 3 months after that.
Publications & conference data
8 peer-reviewed publications reference this trial (live from Europe PMC):
NCT06439693 — The SAPPHO Study: Sequential Therapy With Curative Intent in de Novo HER2+ Metastatic Breast Cancer
· Phase 2
· recruiting
NCT06968585 — A Study of A166 Versus Trastuzumab Emtansine (T-DM1) in Patients With HER2-Positive Unresectable or Metastatic Breast Ca
· Phase 3
· active not recruiting
NCT05429684 — Precise Therapy for Refractory HER2 Positive Advanced Breast Cancer
· Phase 3
· unknown
NCT04622319 — A Study of Trastuzumab Deruxtecan (T-DXd) Versus Trastuzumab Emtansine (T-DM1) in High-risk HER2-positive Participants W
· Phase 3
· active not recruiting
NCT04398914 — Pyrotinib, Trastuzumab, Pertuzumab and Nab-paclitaxel as Neoadjuvant Therapy in HER2-positive Breast Cancer
· Phase 2
· active not recruiting
Other recruiting trials for Breast Cancer
Currently open trials in the same condition.
NCT06148038 — CBD for Breast Cancer Primary Tumors
· Phase 1
· recruiting
NCT07405801 — A Phase II Study Evaluating the Efficacy and Safety of Inavolisib Plus Ribociclib Plus Fulvestrant Versus Placebo Plus R
· Phase 2
· recruiting
NCT07285993 — Detection and Outcomes in Metastatic Invasive Lobular Breast Cancer Through Novel F-18 FAP PET
· Phase 2
· recruiting
NCT07510698 — Same-Day Awake Mastectomy With Immediate Breast Reconstruction for Patients With Breast Cancer
· NA
· recruiting
NCT06768931 — Biolosion Combined Standard Neoadjuvant Therapy to Treat Triple-negative Breast Cancer
· Phase 2
· recruiting
Other National Cancer Institute (NCI) trials
Trials by the same sponsor.
NCT07147231 — Testing the Effectiveness of the Anti-cancer Drug Pidnarulex (CX-5461), in Combination With Another Anti-cancer Drug Cem
· Phase 1, PHASE2
· recruiting
NCT07572123 — Evaluating the Addition of Maintenance Immunotherapy Compared to the Usual Treatment of Chemotherapy and Autologous Stem
· Phase 2, PHASE3
· not yet recruiting
NCT07281417 — Testing the Addition of Cemiplimab (REGN2810) to Chemotherapy Treatment Given Prior to Surgery in Patients With Sinonasa
· Phase 2
· recruiting
NCT07012044 — A Study to Find the Highest Dose of Cedazuridine and Decitabine Combination With Filgrastim as a Treatment Option After
· Phase 1
· not yet recruiting
NCT07437950 — Comparing Different Treatment Lengths for Venetoclax in Older People With Newly Diagnosed Acute Myeloid Leukemia (A Myel
· Phase 2
· not yet recruiting
Publications: Europe PMC API search by NCT ID, retrieved 10 June 2026
Drug + disease cross-links: matched in real time against Drug Landscape's normalised drug + company + condition tables
Sponsor: as reported to ClinicalTrials.gov by National Cancer Institute (NCI)
Last refreshed: 11 October 2023
Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT03190967.