Lapatinib in Treating Brain Metastases in Patients With Stage IV Breast Cancer and Brain Metastases

NCT00098605 | Completed Phase 2

• 2 other identifiers: NCI-2012-02934DFCI 04-199
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 1

Brief Summary

Lapatinib may stop the growth of tumor cells by blocking some of the enzymes needed for their growth. This phase II trial is studying how well lapatinib works in treating brain metastases in patients with stage IV breast cancer and brain metastases.

Conditions

Central Nervous System Metastases; HER2-positive Breast Cancer; Male Breast Cancer; Recurrent Breast Cancer; Stage IV Breast Cancer; Tumors Metastatic to Brain

Outcome Measures

Primary Outcomes (1)

• Objective response rate defined as the percentage of patients with a complete response (CR) or partial response (PR) in the CNS

  A 95% confidence interval (CI) for percent of patients with CNS response will be calculated if the study does not terminate accrual early. The method of Atkinson and Brown will be used to calculate the CI conditional on the sequential design.

  Up to 5 years

Secondary Outcomes (7)

• Objective response in non-CNS sites

  Up to 5 years

• Site of first progression

  At the time of disease progression

• Time to progression (TTP)

  From study entry to the first documented evidence of disease progression, assessed up to 5 years

• Overall survival

  From study entry until death due to any cause, assessed up to 5 years

• Quality of life assessed using the European Organization for the Research and Treatment of Cancer (EORTC) Quality-of-Life Questionnaire Core Cancer Module (QLQ-C30) and EORTC Brain Cancer Module (BCM-20)

  Baseline

Study Arms (1)

Treatment (lapatinib ditosylate)

EXPERIMENTAL

Patients receive oral lapatinib twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Drug: lapatinib ditosylate; Other: laboratory biomarker analysis; Procedure: quality-of-life assessment; Other: questionnaire administration

Interventions

lapatinib ditosylate DRUG

Given orally

Also known as: GSK572016, GW-572016, GW2016, Lapatinib, Tykerb

Treatment (lapatinib ditosylate)

laboratory biomarker analysis OTHER

Correlative studies

Treatment (lapatinib ditosylate)

quality-of-life assessment PROCEDURE

Ancillary studies

Also known as: quality of life assessment

Treatment (lapatinib ditosylate)

questionnaire administration OTHER

Ancillary studies

Treatment (lapatinib ditosylate)

Eligibility Criteria

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

You may qualify if:

• Patients must have histologically or cytologically confirmed invasive breast cancer, with stage IV disease
• HER2 overexpressing breast cancer, defined as 3+ staining by immunohistochemistry (IHC), or 2+ staining by IHC in conjunction with HER2 gene amplification by fluorescent in situ hybridization (FISH), or HER2 gene amplification by FISH alone (in patients whose tumor blocks were not assessed by IHC); patients with tumors that are 2+ by IHC but negative by FISH assay are ineligible
• At least one measurable lesion in the CNS, defined as any lesion \>= 10 mm in longest dimension on T1-weighted, gadolinium-enhanced MRI
• One of the following:
• Cohort 1: Prior treatment of CNS metastases with whole brain radiotherapy (WBRT) and/or stereotactic radiosurgery (SRS), OR;
• Cohort 2: Asymptomatic CNS metastases discovered on a screening radiological study without prior WBRT or SRS
• Disease progression in the CNS, as assessed by at least one of the following:
• New neurological signs or symptoms
• New lesions in the CNS on an imaging study
• Progressive lesions on an imaging study
• Note: patients with progressive lesions are not required to meet Response Evaluation Criteria in Solid Tumors (RECIST) criteria for progression in order to be eligible for this study
• Prior treatment with trastuzumab, either alone or in combination with chemotherapy is required; trastuzumab will be discontinued at least 2 weeks prior to enrollment on study; note: patients who have documented CNS-only metastases are not required to have had prior treatment with trastuzumab; in this situation, the absence of extra-CNS disease must be documented with a physical examination, CT scan of the chest, abdomen, and pelvis, and bone scan
• At least 2 weeks since prior radiotherapy, last chemotherapy, immunotherapy, biologic therapy, or hormonal therapy for cancer, and sufficiently recovered or stabilized from side effects associated with prior therapy; concurrent treatment with bisphosphonates is permitted
• At least 3 weeks since major surgical procedures
• At least 2 weeks since last dose of trastuzumab

You may not qualify if:

• Absolute neutrophil count (ANC) \>= 1.0 x 10\^9/L
• Patients who have had chemotherapy or radiotherapy within 2 weeks prior to entering the study or who have unresolved or unstable, serious toxicity from prior administration of another investigational drug and/or of prior cancer treatment
• Patients may not be receiving any other investigational agents
• Patients may not be receiving concurrent chemotherapy, radiation therapy, immunotherapy, biologic therapy (including an ErbB1 and/or ErbB2 inhibitor), or hormonal therapy for treatment of their cancer; concurrent treatment with bisphosphonates is allowed
• Patients with leptomeningeal carcinomatosis as the only site of CNS involvement will be excluded from this clinical trial, because disease is not measurable, and standard treatment options may differ
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to GW572016
• Concurrent treatment with medications that are either inducers or inhibitors of CYP3A4 is prohibited; some common examples are phenytoin, carbamazepine, and phenobarbital; if a patient requires an anticonvulsant, valproic acid or levetiracetam (Keppra) may be substituted, under the direction of his/her treating physician and/or neurologist
• Malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel; subjects with active ulcerative colitis are also excluded
• History of immediate or delayed hypersensitivity reaction to gadolinium contrast agents, or other contraindication to gadolinium contrast
• Other known contraindication to MRI, such as a cardiac pacemaker, implanted cardiac defibrillator, brain aneurysm clips, cochlear implant, ocular foreign body, or shrapnel
• Concurrent disease or condition that would make the subject inappropriate for study participation, or any serious medical or psychiatric disorder that would interfere with the subject's safety
• Dementia, altered mental status, or any psychiatric condition that would prohibit the understanding or rendering of informed consent
• Pre-existing severe cerebral vascular disease, such as stroke involving a major vessel, CNS vasculitis, or malignant hypertension
• Active cardiac disease, defined as:
• History of uncontrolled or symptomatic angina

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

Dana-Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

MeSH Terms

Conditions

Breast Neoplasms, Male; Breast Neoplasms; Brain Neoplasms

Interventions

Lapatinib; N-(3-chloro-4-((3-fluorobenzyl)oxy)phenyl-6-(5-((methylsulfonyl)ethyl)aminomethyl)-2-furyl)-4-quinazolinamine

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

Study Officials

• Eric Winer

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 7, 2004
• First Posted: December 8, 2004
• Study Start: October 1, 2004
• Primary Completion: September 1, 2006
• Last Updated: June 6, 2013

Record last verified: 2013-06

Locations

US (1)