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

NCT00470847 | Completed Phase 1 Results DMC

• 1 other identifier: 06-356
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 3

Brief 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). 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.

Conditions

Breast Cancer; Brain Metastases

Keywords

Herceptin; breast cancer; radiation therapy; stereotactic radiosurgery; SRS; whole brain radiation; WBRT

Outcome Measures

Primary Outcomes (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.

  5 Years

Secondary Outcomes (5)

• Progression Free Survival

  5 years

• Objective Response Rate in Central Nervous System Sites

  5 years

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

  5 years

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

  5 years

• Overall Survival

  Participants were followed for an average of 3.8 years

Study Arms (1)

Lapatinib,Whole Brain Radiation,Herceptin

OTHER

Lapatinib before and during Whole Brain Radiation Therapy (WBRT), then Herceptin 4mg/kg IV weekly

Drug: Lapatinib; Procedure: Whole Brain Radiation; Drug: Herceptin

Interventions

Lapatinib DRUG

Orally twice daily

Also known as: Tykerb

Lapatinib,Whole Brain Radiation,Herceptin

Whole Brain Radiation PROCEDURE

15 treatments over a period of 3 weeks

Lapatinib,Whole Brain Radiation,Herceptin

Herceptin DRUG

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

Also known as: Trastuzumab

Lapatinib,Whole Brain Radiation,Herceptin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• years of age or older
• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Nancy Lin, MD: lead
• Brigham and Women's Hospital: collaborator
• Breast Cancer Research Foundation: collaborator
• GlaxoSmithKline: collaborator

Study Sites (3)

Indiana University Melvin and Bren Simon Cancer Center

Indianapolis, Indiana, 46202, United States

Location

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

MeSH Terms

Conditions

Breast Neoplasms; Brain Neoplasms

Interventions

Lapatinib; Trastuzumab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Central Nervous System Neoplasms; Nervous System Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Nancy Lin, MD
• Organization: Dana-Farber Cancer Institute

nlin@partners.org

617-632-2335

Study Officials

• Nancy Lin, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: May 7, 2007
• First Posted: May 8, 2007
• Study Start: April 1, 2007
• Primary Completion: December 1, 2009
• Study Completion: June 1, 2012
• Last Updated: May 22, 2014
• Results First Posted: January 20, 2014

Record last verified: 2014-04

Locations

US (3)