Phase 2
N=143
Whole-Brain Radiation Therapy or Stereotactic Radiosurgery With or Without Lapatinib Ditosylate in Treating Patients With Brain Metastasis From HER2-Positive Breast Cancer
HER2-Positive Breast Carcinoma · Invasive Breast Carcinoma · Metastatic Malignant Neoplasm in the Brain · Recurrent Breast Carcinoma · Stage IV Breast Cancer AJCC v6 and v7
Bottom Line
View on ClinicalTrials.gov: NCT01622868 ↗Enrolled (actual)
143
Serious AEs
24.6%
Results posted
Apr 2021
Primary outcome: Primary: Complete Response (CR) Rate in the Brain at 12 Weeks Post-radiation Therapy (RT) Using the RECIST 1.1 Criteria Based on Brain Magnetic Resonance Imaging (MRI) — 5.8; 0 percentage of participants — p=0.97
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Laboratory Biomarker Analysis (Other); Lapatinib Ditosylate (Drug); Stereotactic Radiosurgery (Radiation); Whole-Brain Radiotherapy (Radiation)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- National Cancer Institute (NCI)
- Primary completion
- Dec 2019
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Complete Response (CR) Rate in the Brain at 12 Weeks Post-radiation Therapy (RT) Using the RECIST 1.1 Criteria Based on Brain Magnetic Resonance Imaging (MRI) |
5.8; 0 | 0.97 |
| SECONDARY Complete Response Rate in the Brain at 4 Weeks Post-RT Using the RECIST 1.1 Criteria Based on Brain MRI |
3.6; 1.5 | 0.78 |
| SECONDARY Complete Response Rate in the Brain Using the World Health Organization (WHO)/Modified McDonald Criteria Based on Brain MRI |
3.6; 1.5; 5.8; 0 | 0.78 |
| SECONDARY Objective Response Rate in the Brain Using the RECIST 1.1 Criteria Based on Brain MRI |
41.8; 55.2; 59.6; 46.9 | — |
| SECONDARY Percentage of Participants With Progression in the Brain Outside the Targeted Measurable Disease Using the RECIST 1.1 Criteria Based on Brain MRI |
22.0; 37.7 | — |
| SECONDARY Targeted Lesion-specific Objective Response Rate Using the RECIST 1.1 Measurement Criteria Based on Brain MRI |
51.1; 56.0; 75.0; 61.4 | — |
| SECONDARY Targeted Lesion-specific Progression Rate Using the RECIST 1.1 Measurement Criteria Based on Brain MRI |
3.3; 1.7; 6.6; 14.9 | — |
| SECONDARY Frequency of Highest Treatment-related Adverse Event Per Participant |
8; 14; 23; 20; 5; 20 | — |
| SECONDARY Overall Complete Response Rate in the Brain Using the RECIST 1.1 Criteria Based on Brain MRI |
0; 0 | 1.00 |
| SECONDARY Overall Progression Rate in the Brain Using the RECIST 1.1 Criteria Based on Brain MRI |
38; 54 | — |
| SECONDARY Overall Survival (OS) |
15.6; 15.3 | 0.67 |
Summary
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.
Eligibility 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 unirradiated parenchymal brain metastasis within 21 days prior to study entry; patients who are to undergo SRS must have no more than 10 brain metastases; there is no limit on number of brain metastases for WBRT; 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 (within 21 days prior to study entry)
- Platelets >= 70, 000 cells/mm^3 (within 21 days prior to study entry)
- Hemoglobin >= 8.0 g/dL (note: the use of transfusion or other intervention to achieve hemoglobin [Hgb] >= 8.0 g/dL is acceptable) (within 21 days prior to study entry)
- Creatinine 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
Data sourced from ClinicalTrials.gov (NCT01622868). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.