We are updating the design of this site. Learn more.
Show more
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 1 of 1 for:    NCT 01622868
Previous Study | Return to List | Next Study

Whole-Brain Radiation Therapy or Stereotactic Radiosurgery With or Without Lapatinib Ditosylate in Treating Patients With Brain Metastasis From HER2-Positive Breast Cancer

This study is currently recruiting participants.
Verified November 2017 by National Cancer Institute (NCI)
Sponsor:
ClinicalTrials.gov Identifier:
NCT01622868
First Posted: June 19, 2012
Last Update Posted: December 11, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Information provided by (Responsible Party):
National Cancer Institute (NCI)
  Purpose
This randomized phase II trial studies how well whole-brain radiation therapy or stereotactic radiosurgery with or without lapatinib ditosylate works in treating patients with breast cancer that has too many of a protein called human epidermal growth factor receptor 2 (HER2) on its cells and has spread to the brain. Radiation therapy uses high energy x rays to kill tumor cells and shrink tumors. Stereotactic radiosurgery is a specialized radiation therapy that delivers a single, high dose of radiation directly to the tumor and may kill more tumor cells and cause less damage to normal tissue. Lapatinib ditosylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known whether whole-brain radiation therapy or stereotactic radiosurgery together with lapatinib ditosylate is an effective treatment for brain metastasis from breast cancer.

Condition Intervention Phase
ERBB2 Gene Amplification HER2 Positive Breast Carcinoma Invasive Breast Carcinoma Metastatic Malignant Neoplasm in the Brain Recurrent Breast Carcinoma Stage IV Breast Cancer AJCC v6 and v7 Other: Laboratory Biomarker Analysis Drug: Lapatinib Ditosylate Radiation: Stereotactic Radiosurgery Radiation: Whole-Brain Radiotherapy Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II Randomized Study of Whole Brain Radiotherapy/Stereotactic Radiosurgery in Combination With Concurrent Lapatinib in Patients With Brain Metastasis From HER2-Positive Breast Cancer: A Collaborative Study of NRG Oncology and KROG

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • CR rate in the measurable brain metastases measured by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 based on MRI scan of the brain [ Time Frame: 12 weeks ]
    Response in the brain also will be measured using bidimensional measurements (World Health Organization [WHO]/modified McDonald's criteria).


Secondary Outcome Measures:
  • CNS progressive disease outside the targeted measurable disease [ Time Frame: Up to 4 weeks ]
  • CR rate of measurable brain metastases measured using revised RECIST version 1.1 based on MRI scan of the brain [ Time Frame: 4 weeks ]
    Response in the brain also will be measured using bidimensional measurements (WHO/modified McDonald's criteria).

  • Incidence of treatment-related toxicity as measured by Common Terminology Criteria for Adverse Events version 4 [ Time Frame: Up to 12 weeks post WBRT ]
  • Objective response rate (ORR) (CR + PR) of measurable brain metastases measured using RECIST version 1.1 based on MRI scan of the brain [ Time Frame: At 4 weeks ]
  • ORR (CR + PR) of measurable brain metastases measured using RECIST version 1.1 based on MRI scan of the brain [ Time Frame: At 12 weeks ]
  • OS [ Time Frame: From the date of randomization to the date of first failure, assessed up to 6 years ]
    Estimated by the Kaplan-Meier method. The Cox proportional hazard regression model will be used to analyze the effects of factors, in addition to treatment, that may be associated with OS.

  • Overall CNS complete response [ Time Frame: Up to 2 years ]
  • Overall CNS progressive disease [ Time Frame: Up to 4 weeks ]
  • Targeted lesion-specific progression [ Time Frame: At 4 weeks ]
  • Targeted lesion-specific progression [ Time Frame: At 12 weeks ]

Estimated Enrollment: 143
Actual Study Start Date: July 26, 2012
Estimated Primary Completion Date: February 28, 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm A (WBRT or SRS)
Patients undergo WBRT 5 days a week for 3 weeks for a total of 15 treatments, or SRS for 1 treatment.
Other: Laboratory Biomarker Analysis
Correlative studies
Radiation: Stereotactic Radiosurgery
Undergo SRS
Other Names:
  • Stereotactic External Beam Irradiation
  • stereotactic external-beam radiation therapy
  • stereotactic radiation therapy
  • Stereotactic Radiotherapy
  • stereotaxic radiation therapy
  • stereotaxic radiosurgery
Radiation: Whole-Brain Radiotherapy
Undergo WBRT
Other Names:
  • WBRT
  • whole-brain radiation therapy
Experimental: Arm B (lapatinib ditosylate, WBRT or SRS)
Patients undergo WBRT or SRS as in Arm A. Patients also receive lapatinib ditosylate PO QD for 6 weeks.
Other: Laboratory Biomarker Analysis
Correlative studies
Drug: Lapatinib Ditosylate
Given PO
Other Name: Tykerb
Radiation: Stereotactic Radiosurgery
Undergo SRS
Other Names:
  • Stereotactic External Beam Irradiation
  • stereotactic external-beam radiation therapy
  • stereotactic radiation therapy
  • Stereotactic Radiotherapy
  • stereotaxic radiation therapy
  • stereotaxic radiosurgery
Radiation: Whole-Brain Radiotherapy
Undergo WBRT
Other Names:
  • WBRT
  • whole-brain radiation therapy

Detailed Description:

PRIMARY OBJECTIVES:

I. To determine if there is a signal for an increase in complete response (CR) rate in the measurable brain metastases at 12 weeks post radiation therapy (RT) (whole brain or stereotactic radiosurgery [SRS]) as determined by magnetic-resonance imaging (MRI) scan of the brain, with the addition of lapatinib (lapatinib ditosylate) to WBRT/SRS compared to WBRT/SRS alone.

SECONDARY OBJECTIVES:

I. To evaluate CR rate of the measurable brain metastases at 4 weeks post RT (WBRT/SRS) as determined by MRI scan of the brain, with the addition of lapatinib to WBRT/SRS compared to WBRT/SRS alone.

II. To evaluate objective response rate of measurable brain metastases at 4 and 12 weeks post RT (WBRT/SRS) as determined by MRI scan of the brain, with the addition of lapatinib to WBRT/SRS compared to WBRT/SRS alone.

III. To evaluate targeted lesion-specific objective response rate (CR + partial response [PR]) at 4 and 12 weeks post WBRT/SRS.

IV. To evaluate central nervous system (CNS) progressive disease outside the targeted measurable disease with addition of lapatinib to WBRT/SRS compared to WBRT/SRS alone.

V. To evaluate targeted lesion-specific progression at 4 and 12 weeks post WBRT/SRS.

VI. To evaluate treatment related adverse events when adding lapatinib to WBRT/SRS compared to WBRT/SRS alone.

VII. To evaluate overall CNS complete response: disappearance of all CNS target lesions sustained for at least 4 weeks; with no new lesions, no use of corticosteroids, and patient is stable or improved clinically, when adding lapatinib to WBRT/SRS compared to WBRT/SRS alone.

VIII. To evaluate overall CNS progressive disease (within or outside targeted measurable disease) with addition of lapatinib to WBRT/SRS compared to WBRT/SRS alone.

IX. To evaluate overall survival when adding lapatinib to WBRT/SRS compared to WBRT/SRS alone.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM A: Patients undergo WBRT 5 days a week for 3 weeks for a total of 15 treatments or SRS for 1 treatment.

ARM B: Patients undergo WBRT or SRS as in Arm A. Patients also receive lapatinib ditosylate orally (PO) once daily (QD) for 6 weeks.

After completion of study treatment, patients are followed up at 4 and 12 weeks and then every 12 weeks thereafter.

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Pathologically (histologically or cytologically) proven diagnosis of invasive breast cancer
  • HER2-overexpressing breast cancer (3+ staining by immunohistochemistry or HER2 gene amplification by fluorescent in situ hybridization [FISH] or silver in situ hybridization [SISH] >= 2.0)
  • At least 1 measurable and no more than 10 unirradiated parenchymal brain metastasis within 21 days prior to study entry; the minimum size as measured on T1-weighted gadolinium-enhanced MRI must be as follows according to the number of brain metastases:

    • For a single solitary lesion the size must be >= 10 mm
    • For 2 or more lesions, the size of at least 2 of the lesions must be >= 5 mm
    • Patients may also have the following provided the size requirements above are met:

      • Progressive parenchymal brain metastasis following stereotactic radiosurgery for 1-3 brain metastases, with at least 1 new measurable brain lesion
      • Progressive parenchymal brain metastasis following surgical resection of 1-3 brain metastases, with at least 1 measurable brain lesion
  • History/physical examination within 21 days prior to study entry
  • Karnofsky performance status >= 60 within 21 days prior to study entry
  • Able to swallow and retain oral medication (note: for patients unable to swallow tablets, an oral suspension preparation is acceptable)
  • Absolute neutrophil count (ANC) >= 1,200 cells/mm^3
  • Platelets >= 70,000 cells/mm^3
  • Hemoglobin >= 8.0 g/dL (note: the use of transfusion or other intervention to achieve hemoglobin [Hgb] >= 8.0 g/dL is acceptable)
  • Creatinine < 1.5 times institutional upper limit of normal
  • Bilirubin < 1.5 times institutional upper limit of normal
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 3.0 times institutional upper limit of normal with or without liver metastasis
  • Patient must provide study specific informed consent prior to study entry
  • Women of childbearing potential must have a negative serum pregnancy test within 21 days prior to study entry
  • Sexually active women of childbearing potential and sexually active men must practice adequate contraception during therapy and for 12 months after protocol treatment completion
  • Prior lapatinib is allowed as long as the last dose received was > 21 days prior to study entry and provided the patient has not received it at any time after the diagnosis of brain metastasis

Exclusion Criteria:

  • Prior WBRT
  • Prior radiation therapy (RT) (any site) with concurrent lapatinib defined as 1 or more days on which the patient received both radiation therapy and lapatinib on the same day
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • Prior invasive malignancy (except non-melanomatous skin cancer, curatively resected thyroid papillary carcinoma, and invasive and non-invasive cancers related to the breast cancer) unless disease free for a minimum of 3 years
  • Leptomeningeal disease
  • Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields except patients who have progressed following stereotactic radiosurgery for 1-3 brain metastases, with at least one new lesion
  • Severe, active co-morbidity, defined as follows:

    • Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months
    • Transmural myocardial infarction within the last 6 months
    • Acute bacterial or fungal infection requiring intravenous antibiotics at the time of study entry
    • Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of study entry
    • Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects; hepatic or biliary disease that is acute or currently active or that requires antiviral therapy (with the exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases, or stable chronic liver disease per investigator assessment)
    • History of left ventricular ejection fraction (LVEF) below institutional normal unless repeated and within institutional normal range within 90 days of study entry
  • Grade 2 or greater rash of any cause at time of study entry
  • Grade 2 or greater diarrhea of any cause at time of study entry
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01622868


  Show 292 Study Locations
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
Principal Investigator: In Kim NRG Oncology
  More Information

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT01622868     History of Changes
Other Study ID Numbers: NCI-2012-01977
NCI-2012-01977 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
RTOG-1119
CDR0000735353
RTOG-1119 ( Other Identifier: NRG Oncology )
RTOG-1119 ( Other Identifier: CTEP )
U10CA180868 ( U.S. NIH Grant/Contract )
U10CA021661 ( U.S. NIH Grant/Contract )
First Submitted: June 15, 2012
First Posted: June 19, 2012
Last Update Posted: December 11, 2017
Last Verified: November 2017

Additional relevant MeSH terms:
Carcinoma
Breast Neoplasms
Neoplasms
Neoplasms, Second Primary
Brain Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms by Site
Breast Diseases
Skin Diseases
Central Nervous System Neoplasms
Nervous System Neoplasms
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Lapatinib
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action