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Breast CancerPhase 1NCT00470847

Lapatinib in Combination With Radiation Therapy in Patients With Brain Metastases From HER2-Positive Breast Cancer

A Phase 1 study testing Lapatinib, Whole Brain Radiation and Herceptin in people with Breast Cancer and Brain Metastases, run by Nancy Lin, MD at 3 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The purpose of this research study is to determine the safety of combining lapatinib plus radiation in patients with breast cancer that has spread to the brain. Depending upon the participants cancer, they may also have stereotactic radiosurgery (SRS). Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Breast Cancer, Brain Metastases
What is being tested?
Lapatinib, Whole Brain Radiation and Herceptin
Could I receive a placebo?
No, everyone receives an active treatment
How many people
35 participants
Where
3 sitesUnited States
Study dates
Apr 2007to Jun 2012
Phase
Phase 1
Are there results?
Yes, posted in the registrySummary in the doctors' view

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 or cytologically-confirmed invasive breast cancer
  • HER2 overexpressing breast cancer defined as 3+ staining by immunohistochemistry, or HER2 gene amplification by FISH
  • At least one parenchymal brain metastasis
  • Disease progression in the CNS as assessed by at least one of the following; new neurological signs or symptoms; new lesion(s) in the CNS on an imaging study; progressive lesions on an imaging study
  • At least two weeks since prior radiotherapy, last chemotherapy, immunotherapy, biologic therapy, or major surgery for cancer
  • 18 years of age or older
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  • Life expectancy of greater than 12 weeks
  • ECOG performance status 0-2
  • Normal organ and marrow function as described in the protocol
  • Left ventricular ejection fraction > 50%
  • Able to swallow and retain oral medications

Who cannot join

  • Prior WBRT
  • Receiving any other investigational agents
  • Concurrent chemotherapy, immunotherapy, biologic therapy or hormonal therapy for treatment of their cancer
  • History of grade 3 or 4 allergic reactions attributed to compounds of similar chemical or biologic composition to herceptin or lapatinib
  • Leptomeningeal carcinomatosis as the only site of CNS involvement
  • Concurrent treatment with medications that are either inducers of inhibitors of CYP3A4
Show all 12Show fewer
  • Malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel or active ulcerative colitis
  • History of immediate or delayed hypersensitivity reaction to gadolinium contrast agents
  • Other known contraindication to MRI
  • Uncontrolled intercurrent illness
  • History of other active malignancy except curatively treated basal cell carcinoma or squamous cell carcinoma of the skin, or carcinoma in situ of the cervix
  • Pregnant or breastfeeding women

Trial locations and contacts

3 sites in 1 country.

United States3 sites

  • Brigham and Women's Hospital

    Boston, Massachusetts, 02115

  • Dana-Farber Cancer Institute

    Boston, Massachusetts, 02115

  • Indiana University Melvin and Bren Simon Cancer Center

    Indianapolis, Indiana, 46202

Other trials in United States

About this study

Official title: A Phase I Study of Lapatinib in Combination With Radiation Therapy in Patients With Brain Metastases From HER2-Positive Breast Cancer

The purpose of this research study is to determine the safety of combining lapatinib plus radiation in patients with breast cancer that has spread to the brain. Depending upon the participants cancer, they may also have stereotactic radiosurgery (SRS). Lapatinib s a compound that may stop cancer cells from growing abnormally. It is thought that lapatinib might also make cancer cells more sensitive to radiation. This drug has been used in other research studies in women with breast cancer, and information from those other research studies suggests that lapatinib may help to shrink or stabilize breast tumors both inside the brain and outside the brain.

Read the detailed description
  • Participant's will be given a study medication-dosing calendar for each treatment cycle. Each treatment cycle lasts four weeks. On the first day of the treatment cycle, participants will take 1 lapatinib orally twice per day, 12 hours apart. After the first day, lapatinib will be taken once a day in the morning.
  • Whole brain radiation treatments will begin approximately 1-8 days after the first dose of lapatinib. The radiation treatments will follow standard guidelines and will be supervised by a radiation oncologist. Radiation will be given in 15 treatments over a period of three weeks.
  • Some participants will also undergo stereotactic radiosurgery (SRS). SRS is a highly focused and intense form of radiation treatment generally done as an outpatient procedure in a single treatment.
  • After whole brain radiation treatments are completed, lapatinib will be continued at the same dose for one more week. After that, the lapatinib dose may change. In addition at the same time, Herceptin will be started. Participants will continue with both lapatinib and herceptin together as long as there is evidence that they are benefitting from it.
  • During all treatment cycles participants will have a physical exam and be asked general questions about their health. Photographs will be taken of the tumor, if visible, to assess the response of the tumor to the treatment. An assessment of the tumor by CT scan of the body, and MRI imaging of the brain will be performed every two months. An assessment of heart function by MUGA scan or echocardiogram will be performed every 8 weeks. The participant will also be asked to complete a brief questionnaire measuring quality of life and asking about symptoms related to the cancer at baseline, 6 months, and one year. Blood tests will be performed every 4 weeks.
Being tested
Lapatinib, Whole Brain Radiation, Herceptin
Keywords
Herceptin, breast cancer, radiation therapy, stereotactic radiosurgery, SRS, whole brain radiation, WBRT
Medical subject headings
Breast Neoplasms, Brain Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • LapatinibDrug

    Also called Tykerb

    Orally twice daily

  • Whole Brain RadiationProcedure or surgery

    15 treatments over a period of 3 weeks

  • HerceptinDrug

    Also called Trastuzumab

    Herceptin 4mg/kg loading dose then 2 mg/kg IV once weekly, then once every three weeks after cycle 3.

Study groups in NCT00470847
Study groupRoleWhat they receive
Lapatinib,Whole Brain Radiation,HerceptinOtherLapatinib before and during Whole Brain Radiation Therapy (WBRT), then Herceptin 4mg/kg IV weekly
Receives: Drug: Lapatinib; Procedure: Whole Brain Radiation; Drug: Herceptin

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. The Maximum Tolerated Dose of Lapatinib When Combined With Cranial Radiation in Patients With CNS Metastases From HER2-positive Breast Cancer.

    The maximum tolerated dose is defined as :The highest dose of a drug or treatment that does not cause unacceptable side effects.

    Measured: 5 Years

Secondary outcomes (5)

  1. Progression Free Survival

    Progression Free Survival is the time from date of start of treatment to the date of the first documented progression or death due to any cause. If a patient has not progressed or died, progression free survival is censored at the time of last tumor assessment. Progression is defined using Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.0), as a 20 % increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

    Measured: 5 years

  2. Objective Response Rate in Central Nervous System Sites

    Objective Response Rate was defined using volumetric response as the following: Complete Response (CR) is the disappearance of all target lesions, stable/responsive non-target lesions, and no new lesions. Partial response (PR) is at least a 50% reduction in the sum of the target lesions, stable/responsive non-target lesions, and no new lesions. Stable Disease (SD) is neither CR PR or Progressive Disease (PD). And Progressive Disease (PD) is at least 40% increase in sum of target lesionsor the appearance of any new lesion >=6mm in the longest dimension. If a patient progressed in a non-central nervous system(CNS) site first, died, or withdrew from the study for any reason after the first dose of drug was administered, and before a CR or PR in the central nervous system was determined, she was considered a CNS non-responder.

    Measured: 5 years

  3. Percentage of Participants Having Central Nervous System as the Site of the First Progression

    Measured: 5 years

  4. Percentage of Participants Having Non-Central Nervous System Sites as the Site of First Progression

    Measured: 5 years

  5. Overall Survival

    Overall average length of participant survival after protocol initiation

    Measured: Participants were followed for an average of 3.8 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted8 May 2007 (estimated)
  2. Study startApr 2007
  3. Primary completionDec 2009
  4. Study completionJun 2012

Resources

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 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
35 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00470847
Sponsor's protocol ID
06-356
Status last verified
Apr 2014
First submitted
7 May 2007
Last updated
22 May 2014
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Lapatinib, Whole Brain Radiation and Herceptin in people with Breast Cancer and Brain Metastases, run by Nancy Lin, MD at 3 sites 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 11 inclusion and 12 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: finished, as of the sponsor's last update on 22 May 2014. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 20 Jan 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

The Maximum Tolerated Dose of Lapatinib When Combined With Cranial Radiation in Patients With CNS Metastases From HER2-positive Breast Cancer. (time frame: 5 Years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00470847.

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 22 May 2014.

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