Basic Trial Information
Trial Description
     Summary
     Further Trial Information
     Eligibility Criteria
Trial Contact Information

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase II	Treatment	Active	18 and over	Other	D-0520 NCT00225758

Trial Description

Summary

Two thirds or more of breast cancers are dependent on estrogen for growth. We use a number of estrogen-blocking medicines for treatment of metastatic breast cancer. The treatment response to these agents is unpredictable, however, and approximately one-third of patients with metastatic breast cancer with receptors for estrogen or progesterone have no benefit from hormonal therapy. Nearly all patients with metastatic breast cancer will eventually become resistant to hormonal therapy despite the fact that the hormone receptors are still present.

Some cells make a different class of growth factor receptor called the Epidermal Growth Factor Receptor. There is a growing body of experimental evidence showing that breast cancer cells that make Epidermal Growth Factor Receptors are more resistant to hormonal therapy and have a poorer prognosis.

Several investigators have found that the Epidermal Growth Factor Receptor can activate the estrogen receptor, even in the presence of estrogen-blocking drugs. Growth of these cells can be slowed by blockade of both Epidermal Growth Factor Receptor signaling and estrogen-receptor signaling. Lapatinib is a small molecule which can inhibit two different forms of the Epidermal Growth Factor Receptor. It has been studied in people with a number of different cancers, including breast cancer, and a safe dose and its common side effects have been defined.

Our hypothesis is that the Epidermal Growth Factor Receptor is the dominant receptor pathway used by breast cancers in our patients with hormone-resistant tumors. Drugs like lapatinib which block several forms of the Epidermal Growth Factor Receptor would best be able to reverse resistance to hormonal agents.

Further Study Information

All patients must have stopped their endocrine two to four weeks or longer prior to entry on study. Upon enrollment, patients will begin lapatinib at 1500 mg once a day orally. The original endocrine therapy will resume two weeks later. The lapatinib will be continued for a maximum of 26 weeks.

A history, physical examination, blood counts, and chemistries will be done at baseline, and at regular intervals through the course of the study. A CT scan and bone scan will be done prior to treatment and at weeks 14 and 26. Assays for plasma DNA will be performed on blood sampled at baseline and at multiple time points throughout the course of treatment. Percutaneous biopsies will be taken in selected patients with accessible disease, 72 hours or less prior to the start of lapatinib, and again 13-15 days, and 27-29 days following the start of lapatinib. The day 13-15 biopsy will be done just prior to the resumption of the patient's endocrine therapy. Assays for phospho-ERK, phospho-Akt, Cyclin D1, Ki-67, and IRS-1 will be performed by conventional immunohistochemistry on the biopsied tissue.

Eligibility Criteria

Inclusion Criteria:

• Patients with histologically or cytologically proven metastatic breast cancer.

• Patients with either estrogen or progesterone receptor positivity on the most recently examined tumor biopsy.

• Patients must have most recently been using an anti-estrogen (tamoxifen, toremifene, raloxifene, or fulvestrant) or an aromatase inhibitor.

• Patients must have had either a partial response or better, or stable disease for 24 weeks or longer, followed by disease progression, on the current or most recent hormonal therapy for management of metastatic breast cancer.

• Patients must be enrolled within six weeks of defining disease progression on hormonal therapy.

• Patients must have stopped fulvestrant at least four weeks prior and other endocrine therapy at least two weeks prior to enrollment on study.

• Patients must have either measurable disease or at least one evaluable bone lesion that has not been irradiated. Measurable disease is not necessary.

• Estimated life expectancy of at least 6 months.

• ECOG performance status 0-2.

• Adequate hematologic, hepatic, and renal function.

• Patients must be post-menopausal, or they must be practicing either abstinence or an adequate method of contraception, or their sexual partner must be sterile.

• All patients must be able to swallow, retain, and absorb oral medications.

• All patients must be able to give informed consent indicating that they are aware of the investigational nature of this study.

Exclusion Criteria:

• Patients may not have received an investigational agent within the prior four weeks.

• Patients may not have received trastuzumab within three weeks of study entry.

• Patients may not have had major surgery within the prior two weeks.

• Patients may not have Class III or IV heart failure as defined by the NYHA functional classification system.

• Patients may not have a left ventricular ejection fraction < 40% based on MUGA or echocardiogram.

• Patients may not have uncontrolled brain metastases or leptomeningeal disease.

• Patients may not have rapidly progressive visceral metastases.

• Patients may not have a serious illness or conditions including clinically significant cardiac disease, angina pectoris, serious psychiatric disorder, or an active infection.

• Patients may not be receiving concurrent medications (listed in the protocol) which may interact with lapatinib during treatment with lapatinib.

Trial Contact Information

Trial Lead Organizations/Sponsors

Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center

Gary N Schwartz, MD

Principal Investigator

Gary N Schwartz, MD		Ph: (603) 653-6181
		Email: gary.n.schwartz@hitchcock.org

Michelle L Greene		Ph: (603) 653-6196
		Email: michelle.l.greene@hitchcock.org

U.S.A.
Colorado
	Aurora
		Virginia F. Borges	Principal Investigator
	University of Colorado Cancer Center at UC Health Sciences Center
		Megan Rigdon	Ph: 720-848-0630
			Email: megan.rigdon@uchsc.edu
New Hampshire
	Lebanon
		Michelle L Greene	Ph: (603) 653-6196
			Email: michelle.l.greene@hitchcock.org
	Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center
		Gary N Schwartz, MD	Ph: 603-653-6181
			Email: gary.n.schwartz@hitchcock.org
New York
	Lake Success
		Lora Wieselberg, MD	Principal Investigator
	Monter Cancer Center of the North Shore-LIJ Health System
		Marjorie Fricano, RN	Ph: 516-734-8942
			Email: MFricano@nshs.edu

Link to the current ClinicalTrials.gov record.
NLM Identifer NCT00225758
Information obtained from ClinicalTrials.gov on March 18, 2009