Breast Cancer With Brain MetastasisPhase 2NCT01924351
HER2-positive Breast Cancer With Brain Metastasis (GCC 1345)
A Phase 2 study testing Stereotactic Radiosurgery plus HER-2 directed therapy in HER2-positive Breast Cancer with Brain Metastasis in people with Breast Cancer With Brain Metastasis, run by University of Maryland, Baltimore at 1 site in United States.
Trial summary
Primary Objective: To determine if treatment with SRS followed by a HER-2 directed therapy regimen results in a 6-month distant brain relapse rate of less than 30%. Secondary Objectives: 1. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Breast Cancer With Brain Metastasis
- What is being tested?
- Stereotactic Radiosurgery plus HER-2 directed therapy in HER2-positive Breast Cancer with Brain Metastasis
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- Feb 2015to Jun 2016
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologically proven diagnosis HER2-positive breast cancer. Her2-positive is defined as follows:
- Validated IHC assay score of 3+ (defined as uniform, intense staining of >30% of invasive tumor cells)
- OR- Average HER2 gene copy number of >6
- OR- Gene amplified (HER2:D17Z1 ratio >2.20).
- Patients with 1-10 newly diagnosed brain metastases
- The contrast-enhancing intraparenchymal brain tumor must be well circumscribed and must have a maximum diameter of ≤ 4.0 cm in any direction on the enhanced scan. If multiple lesions are present and one lesion is at the maximum diameter, the other(s) must not exceed 3.0 cm in maximum diameter.
Show all 30Show fewer
- History and physical with neurological examination, steroid documentation, height, and weight within 14 days of registration.
- A diagnostic contrast-enhanced MRI of the brain must be performed within 28 days prior to registration.
- Eligibility for treatment with SRS confirmed by a radiation oncologist.
- Performance Status 0-2
- Age ≥ 18.
- CBC with differential obtained within 14 days prior to registration, with adequate bone marrow function defined as follows:
- Absolute neutrophil count (ANC) ≥ 1,100 cells/mm3.
- Platelets ≥ 75,000 cells/mm3.
- Hemoglobin ≥ 9.0 g/dl (Note: The use of transfusion or other intervention to achieve Hgb ≥9.0 g/dl is acceptable).
- Adequate renal function within 14 days prior to registration, as defined below:
- BUN ≤ 30 mg/dl.
- Creatinine ≤ 1.5 x ULN
- Creatinine clearance ≥30 mL/min.
- Adequate hepatic function within 14 days prior to registration, as defined below:
- Total Bilirubin ≤1.5 x ULN
- ALT/AST ≤ 2.5 x upper limit of normal (ULN).
- Systolic blood pressure ≤ 160 mg Hg or diastolic pressure ≤ 90 mg Hg within 14 days prior to registration.
- Prothrombin time/international normalized ratio (PT INR) < 1.4 for patients not on warfarin confirmed by testing within 14 days prior to registration. Patients on full-dose anticoagulants (e.g., warfarin or LMW heparin) must meet both of the following criteria:
- No active bleeding or pathological condition that carries a high risk of bleeding (e.g., tumor involving major vessels or known varices).
- In-range INR (between 2.5 and 3.5) on a stable dose of warfarin-based oral anticoagulant; or on a stable dose of low molecular weight heparin; or INR between 1.5 and 2 if a Greenfield filter is in place.
- Patient must provide study specific informed consent prior to study entry.
- For women of child-bearing potential, negative serum pregnancy test within 14 days prior to registration.
- Women of childbearing potential and male participants must practice adequate contraception.
- Echocardiogram or MUGA scan with ejection fraction within normal institution limits within 28 days of registration
Who cannot join
- Prior invasive malignancy (except for non-melanomatous skin cancer) unless disease free for ≥ 3 years. For example, carcinoma in situ of the oral cavity and cervix are all permissible.
- Leptomeningeal metastases
- Previous treatment with all of the following: lapatinib, trastuzumab, pertuzumab, and trastuzumab emtansine. (Patients are eligible if treated with 3 or less of these agents.)
- Prior cranial radiotherapy.
- Prior resection of cerebral metastases
- Allergy to gadolinium
Show all 26Show fewer
- Severe, active co-morbidity, defined as follows:
- Unstable angina and/or congestive heart failure within the last 6 months.
- Transmural myocardial infarction within the last 6 months.
- New York Heart Association grade II or greater congestive heart failure requiring hospitalization within 12 months prior to registration.
- History of stroke, cerebral vascular accident (CVA) or transient ischemic attack within 6 months.
- Serious and inadequately controlled cardiac arrhythmia.
- Significant vascular disease (e.g., aortic aneurysm, history of aortic dissection) or clinically significant peripheral vascular disease.
- Evidence of bleeding diathesis or coagulopathy.
- Serious or non-healing wound, ulcer, or bone fracture or history of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess, major surgical procedure or significant traumatic injury within 28 days prior to registration, with the exception of the craniotomy for tumor resection or follow-on craniotomies to manage complications of brain tumor management such as hemorrhage or infection.
- Bacterial or fungal infection requiring intravenous antibiotics at the time of registration.
- Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration.
- Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects; note, however, that laboratory tests for coagulation parameters are not required for entry into this protocol.
- Active connective tissue disorders, such as lupus or scleroderma, that in the opinion of the treating physician may put the patient at high risk for radiation toxicity.
- Any other major medical illnesses or psychiatric impairments that in the investigator's opinion will prevent administration or completion of protocol therapy.
- Cognitive impairment that precludes a patient from acting as his or her own agent to provide informed consent.
- Women of childbearing potential who are sexually active and not willing/able to use medically acceptable forms of contraception; this exclusion is necessary because the chemotherapeutic treatment involved in this study is potentially teratogenic.
- Pregnant or lactating women, due to possible adverse effects on the developing fetus or infant due to study treatment.
- Patients treated on any other therapeutic clinical protocols within 30 days prior to study entry or during participation in the study.
- Inability to undergo MRI (e.g., due to safety reasons, such as presence of a pacemaker).
- Inability to undergo SRS due to claustrophobia
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase II Study of Stereotactic Radiosurgery Plus HER-2 Directed Therapy in HER2-positive Breast Cancer With Brain Metastasis
Primary Objective:
To determine if treatment with SRS followed by a HER-2 directed therapy regimen results in a 6-month distant brain relapse rate of less than 30%.
Read more
Secondary Objectives:
- Describe the natural history of neurocognitive function for women with brain metastases treated with SRS and HER-2 directed systemic therapy and establish a reference benchmark to generate hypothesis for future design of a phase III trial.
- Describe patterns of distant brain relapse after SRS for all patients and compare them between (a) patients with 1-3 vs. 4-10 brain metastasis and (b) between patients treated with each systemic therapy regimen
- Describe patterns of neurologic death
- Describe patterns of local brain relapse
- Describe patterns of re-irradiation with WBRT or SRS
- Describe adverse events
Read the detailed description
Metastatic breast cancer is a leading cause of death for women. HER2(human epidermal growth factor receptor type 2)-positive disease represents a more aggressive type of breast cancer which often afflicts younger patients. As many as one-third of patients with HER2-positive breast cancer develop brain metastasis[1]. The development of brain metastasis in this young female population is particularly devastating as they are often highly functional and may have young children. Improvement in quality of life by preventing neurocognitive decline from disease progression and/or treatment related side effects is paramount.
Patients with 1-10 brain metastasis from HER2+ breast cancer, after informed consent, will be treated with:
Radiosurgery: Gamma-knife, Cyberknife, or linac-based SRS is followed by anti-HER2 based systemic therapy, with the treatment selection of approved agents at the physician's discretion. Possible anti-HER2 agents include trastuzumab, pertuzumab, trastuzumab-emtansine, or lapatinib. Anti-HER2 therapy will be delivered in combination with appropriate cytotoxic therapy as per FDA indications.
Anti-HER2 based systemic therapy will continue until progression, patient discontinuation, unacceptable toxicity or if, in the view of the physician it is no longer indicated.
MRI and neurocognitive testing will be done prior to SRS and repeated every 3 months during the first 6 months from enrollment.
Patients can only be enrolled after all eligibility criteria are met. The date of registration/enrollment is considered to be the day the Eligibility Checklist is signed by the verifying physician. Once a patient is enrolled, a unique case number will be assigned to the patient.
- Conditions
- Breast Cancer With Brain Metastasis
- Being tested
- Stereotactic Radiosurgery plus HER-2 directed therapy in HER2-positive Breast Cancer with Brain Metastasis
- Keywords
- Breast Cancer with Brain Metastasis, HER2-positive, HER-2 therapy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Stereotactic Radiosurgery plus HER-2 directed therapy in HER2-positive Breast Cancer with Brain MetastasisRadiation
| Study group | Role | What they receive |
|---|---|---|
| HER2-positive Breast Cancer with Brain Metastasis | Other | Stereotactic Radiosurgery plus HER-2 directed therapy in HER2-positive Breast Cancer with Brain Metastasis Receives: Radiation: Stereotactic Radiosurgery plus HER-2 directed therapy in HER2-positive Breast Cancer with Brain Metastasis |
What is being measured
The primary outcome is the main question the study is designed to answer.
Relaspe Rate (Primary)
To determine if treatment with SRS followed by a HER-2 directed therapy regimen results in a 6-month distant brain relapse rate of less than 30%.
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Aug 2013 (estimated)
- Study startFeb 2015
- Primary completionJun 2016
- Study completionJun 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Breast Cancer With Brain MetastasisStudies of the same condition, open and under way.
- More trials run by University of Maryland, BaltimoreThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Maryland, Baltimore
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Department of Radiation Oncology, University of Maryland, Baltimore
- Investigators
- Elizabeth Nichols, M.D., Principal investigator, Univerysity of Maryland Baltimore
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01924351
- Sponsor's protocol ID
- HP-00056720
- Status last verified
- Mar 2020
- First submitted
- 13 Aug 2013
- Last updated
- 18 Mar 2020
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 18 Mar 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study of Stereotactic Radiosurgery Plus HER-2 Directed Therapy in HER2-positive Breast Cancer With Brain Metastasis
- ClinicalTrials.gov ID
- NCT01924351
- Acronym / sponsor ID
- HP-00056720
- Conditions
- Breast Cancer With Brain Metastasis
- Keywords
- Breast Cancer with Brain Metastasis, HER2-positive, HER-2 therapy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Withdrawn
- Enrolment
- 0 participants (actual)
- Lead sponsor
- University of Maryland, BaltimoreUniversity, hospital or other
- Study start
- Feb 2015
- Primary completion
- Jun 2016 (actual)
- Study completion
- Jun 2016 (actual)
- First posted
- 16 Aug 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Primary Objective:
To determine if treatment with SRS followed by a HER-2 directed therapy regimen results in a 6-month distant brain relapse rate of less than 30%.
Secondary Objectives:
- Describe the natural history of neurocognitive function for women with brain metastases treated with SRS and HER-2 directed systemic therapy and establish a reference benchmark to generate hypothesis for future design of a phase III trial.
- Describe patterns of distant brain relapse after SRS for all patients and compare them between (a) patients with 1-3 vs. 4-10 brain metastasis and (b) between patients treated with each systemic therapy regimen
- Describe patterns of neurologic death
- Describe patterns of local brain relapse
- Describe patterns of re-irradiation with WBRT or SRS
- Describe adverse events
Detailed description
Metastatic breast cancer is a leading cause of death for women. HER2(human epidermal growth factor receptor type 2)-positive disease represents a more aggressive type of breast cancer which often afflicts younger patients. As many as one-third of patients with HER2-positive breast cancer develop brain metastasis[1]. The development of brain metastasis in this young female population is particularly devastating as they are often highly functional and may have young children. Improvement in quality of life by preventing neurocognitive decline from disease progression and/or treatment related side effects is paramount.
Patients with 1-10 brain metastasis from HER2+ breast cancer, after informed consent, will be treated with:
Radiosurgery: Gamma-knife, Cyberknife, or linac-based SRS is followed by anti-HER2 based systemic therapy, with the treatment selection of approved agents at the physician's discretion. Possible anti-HER2 agents include trastuzumab, pertuzumab, trastuzumab-emtansine, or lapatinib. Anti-HER2 therapy will be delivered in combination with appropriate cytotoxic therapy as per FDA indications.
Anti-HER2 based systemic therapy will continue until progression, patient discontinuation, unacceptable toxicity or if, in the view of the physician it is no longer indicated.
MRI and neurocognitive testing will be done prior to SRS and repeated every 3 months during the first 6 months from enrollment.
Patients can only be enrolled after all eligibility criteria are met. The date of registration/enrollment is considered to be the day the Eligibility Checklist is signed by the verifying physician. Once a patient is enrolled, a unique case number will be assigned to the patient.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| HER2-positive Breast Cancer with Brain Metastasis | Other | Radiation: Stereotactic Radiosurgery plus HER-2 directed therapy in HER2-positive Breast Cancer with Brain MetastasisStereotactic Radiosurgery plus HER-2 directed therapy in HER2-positive Breast Cancer with Brain Metastasis |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (30 listed)
- Histologically proven diagnosis HER2-positive breast cancer. Her2-positive is defined as follows:
- OR- Average HER2 gene copy number of >6
- OR- Gene amplified (HER2:D17Z1 ratio >2.20).
- Patients with 1-10 newly diagnosed brain metastases
- The contrast-enhancing intraparenchymal brain tumor must be well circumscribed and must have a maximum diameter of ≤ 4.0 cm in any direction on the enhanced scan. If multiple lesions are present and one lesion is at the maximum diameter, the other(s) must not exceed 3.0 cm in maximum diameter.
Key exclusion criteria (26 listed)
- Prior invasive malignancy (except for non-melanomatous skin cancer) unless disease free for ≥ 3 years. For example, carcinoma in situ of the oral cavity and cervix are all permissible.
- Leptomeningeal metastases
- Previous treatment with all of the following: lapatinib, trastuzumab, pertuzumab, and trastuzumab emtansine. (Patients are eligible if treated with 3 or less of these agents.)
- Prior cranial radiotherapy.
- Prior resection of cerebral metastases
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Stereotactic Radiosurgery plus HER-2 directed therapy in HER2-positive Breast Cancer with Brain Metastasis | Radiation | HER2-positive Breast Cancer with Brain Metastasis |
Primary outcome
Relaspe Rate (Primary)
Time frame: 12 months
To determine if treatment with SRS followed by a HER-2 directed therapy regimen results in a 6-month distant brain relapse rate of less than 30%.
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Mar 2020.
Related trials for Breast Cancer With Brain Metastasis
RecruitingPhase 2
BrAin Metastasis in tripLe Negateive Breast Cancer: IvoneScimab and Trop2 ADC
Triple-Negative Breast Cancer (TNBC), Brain Metastases
RecruitingObservational study
Collection of CSF Samples From Participants With Metastatic Triple Negative Breast Cancer (TNBC) and HER2+ Breast Cancer With no Prior History Nor Active Radiographically Detectable Brain Metastases
Breast Cancer, Breast Carcinoma
RecruitingPhase 2/3
RO7771950 Versus Tucatinib in Combination With Trastuzumab and Capecitabine in People With Locally Advanced or Metastatic Breast Cancer That is Human Epidermal Growth Factor Receptor 2 (HER2)-Positive
HER2-positive Breast Cancer
Active, not recruitingPhase 2
Phase II Study of Dato-DXd in Triple-negative Breast Cancer Patients With Newly Diagnosed or Progressing Brain Metastases
Breast Cancer Stage IV
RecruitingPhase 4
Brain [18F]-FES PET/CT in Patients With Estrogen-Receptor Positive Breast Cancer
Breast Cancer, Brain Metastases
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Elizabeth Nichols, M.D. principal investigator
Univerysity of Maryland Baltimore
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Stereotactic Radiosurgery plus HER-2 directed therapy in HER2-positive Breast Cancer with Brain Metastasis in people with Breast Cancer With Brain Metastasis, run by University of Maryland, Baltimore at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 30 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 18 Mar 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Relaspe Rate (Primary) (time frame: 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Mar 2020.