Breast Cancer With Brain Metastasis Clinical Trial
Official title:
A Phase II Study of Stereotactic Radiosurgery Plus HER-2 Directed Therapy in HER2-positive Breast Cancer With Brain Metastasis
| NCT number | NCT01924351 |
| Other study ID # | HP-00056720 |
| Secondary ID | |
| Status | Withdrawn |
| Phase | Phase 2 |
| First received | |
| Last updated | |
| Start date | February 2015 |
| Est. completion date | June 2016 |
| Verified date | March 2020 |
| Source | University of Maryland, Baltimore |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
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. 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.
2. 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
3. Describe patterns of neurologic death
4. Describe patterns of local brain relapse
5. Describe patterns of re-irradiation with WBRT or SRS
6. Describe adverse events
| Status | Withdrawn |
| Enrollment | 0 |
| Est. completion date | June 2016 |
| Est. primary completion date | June 2016 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years and older |
| Eligibility |
Inclusion Criteria: - 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. - 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 Exclusion Criteria: - 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 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 |
| Country | Name | City | State |
|---|---|---|---|
| United States | Ummc Msgcc | Baltimore | Maryland |
| Lead Sponsor | Collaborator |
|---|---|
| University of Maryland, Baltimore |
United States,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | 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%. | 12 months |