Clinical Trials /

HER2-positive Breast Cancer With Brain Metastasis (GCC 1345)

NCT01924351

Description:

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

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Withdrawn

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: HER2-positive Breast Cancer With Brain Metastasis (GCC 1345)
  • Official Title: A Phase II Study of Stereotactic Radiosurgery Plus HER-2 Directed Therapy in HER2-positive Breast Cancer With Brain Metastasis

Clinical Trial IDs

  • ORG STUDY ID: HP-00056720
  • NCT ID: NCT01924351

Conditions

  • Breast Cancer With Brain Metastasis

Purpose

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

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.
    

Trial Arms

NameTypeDescriptionInterventions
HER2-positive Breast Cancer with Brain MetastasisOtherStereotactic Radiosurgery plus HER-2 directed therapy in HER2-positive Breast Cancer with Brain Metastasis

    Eligibility Criteria

            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
          
    Maximum Eligible Age:N/A
    Minimum Eligible Age:18 Years
    Eligible Gender:All
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:Relaspe Rate (Primary)
    Time Frame:12 months
    Safety Issue:
    Description: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%.

    Details

    Phase:Phase 2
    Primary Purpose:Interventional
    Overall Status:Withdrawn
    Lead Sponsor:University of Maryland

    Trial Keywords

    • Breast Cancer with Brain Metastasis
    • HER2-positive
    • HER-2 therapy

    Last Updated

    June 7, 2016