Ph II Letrozole + OSI-774 (Tarceva) in Post-menopausal, w/ ER and/or PR-positive Met Breast Cancer.

NCT ID: NCT00611715

Last Updated: 2012-08-09

Study Results

Results available

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Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE2

Total Enrollment

48 participants

Study Classification

INTERVENTIONAL

Study Start Date

2003-11-30

Study Completion Date

2008-12-31

Brief Summary

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RATIONALE: Estrogen can cause the growth of breast cancer cells. Hormone therapy using letrozole may fight breast cancer by blocking the use of estrogen by the tumor cells. Erlotinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving letrozole together with erlotinib may kill more tumor cells.

PURPOSE: This phase II clinical trial is studying how well giving letrozole together with erlotinib works in treating postmenopausal women with estrogen receptor-positive and/or progesterone receptor-positive locally recurrent or metastatic breast cancer.

Detailed Description

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OBJECTIVES:

Primary

* To determine the rate of clinical benefit (complete response \[CR\], partial response \[PR\], and stable disease \[SD\] in patients with hormone-dependent locally recurrent or metastatic breast cancer treated with letrozole in combination with erlotinib hydrochloride.

Secondary

* To determine the time to progression (TTP) in patients treated with this regimen.
* To evaluate the anti-tumor activity, as determined by CR and PR rates, of this regimen in these patients.
* To evaluate the safety of this regimen in these patients.
* To determine if tumors that are positive for epidermal growth factor receptor (EGFR) or Ser118 ER, or that overexpress human epidermal receptor (HER2) exhibit a longer TTP from the combination compared to tumors that do not express or overexpress these molecules.

OUTLINE: This is a multicenter study. Patients are stratified according to prior hormone therapy (hormone-therapy naive/first-line therapy vs prior hormonal therapy with either tamoxifen or an aromatase inhibitor in the adjuvant or metastatic setting/second-line therapy)

Patients receive oral letrozole and oral erlotinib hydrochloride once daily in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed every 3 months for 2 years, every 6 months for 3 years, and then yearly thereafter.

Conditions

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Breast Cancer

Keywords

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recurrent breast cancer stage IV breast cancer

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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First line/hormone-therapy naive

Group Type EXPERIMENTAL

erlotinib hydrochloride

Intervention Type DRUG

OSI-774 150 mg/day

letrozole

Intervention Type DRUG

Letrozole 2.5 mg/day

fluorescence in situ hybridization

Intervention Type GENETIC

To determine HER2 gene amplification or excess copies of the HER2 gene

immunohistochemistry staining method

Intervention Type OTHER

to measure the epidermal growth factor receptors (EGFR)

laboratory biomarker analysis

Intervention Type OTHER

To determine if specific biomarkers exhibit a longer time to tumor progression after treatment with the study drugs

Second-line/prev hormone-therapy tx

Group Type EXPERIMENTAL

erlotinib hydrochloride

Intervention Type DRUG

OSI-774 150 mg/day

letrozole

Intervention Type DRUG

Letrozole 2.5 mg/day

fluorescence in situ hybridization

Intervention Type GENETIC

To determine HER2 gene amplification or excess copies of the HER2 gene

immunohistochemistry staining method

Intervention Type OTHER

to measure the epidermal growth factor receptors (EGFR)

laboratory biomarker analysis

Intervention Type OTHER

To determine if specific biomarkers exhibit a longer time to tumor progression after treatment with the study drugs

Interventions

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erlotinib hydrochloride

OSI-774 150 mg/day

Intervention Type DRUG

letrozole

Letrozole 2.5 mg/day

Intervention Type DRUG

fluorescence in situ hybridization

To determine HER2 gene amplification or excess copies of the HER2 gene

Intervention Type GENETIC

immunohistochemistry staining method

to measure the epidermal growth factor receptors (EGFR)

Intervention Type OTHER

laboratory biomarker analysis

To determine if specific biomarkers exhibit a longer time to tumor progression after treatment with the study drugs

Intervention Type OTHER

Other Intervention Names

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Tarceva, OSI-774 Femara None specified None specified none specified

Eligibility Criteria

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Inclusion Criteria

* Patients must have estrogen (ER) and/or progesterone receptor (PgR)-positive, histologically confirmed adenocarcinoma of the breast with measurable (but not operable) locally recurrent disease, or measurable and/or evaluable metastatic disease (see protocol section 10.3), including isolated bone metastases.
* Patients with available paraffin tissue blocks from either the primary or the metastatic site must submit tissue blocks for retrospective EGFR and HER2 analysis. If tissue blocks cannot be submitted, 20 unstained slides from each paraffin block must be submitted.
* All patients must be post-menopausal females as defined by one of the following:

* Prior bilateral oophorectomy
* Prior bilateral ovarian irradiation
* No menstrual period for 12 months or longer
* If age 55 years or less and \< 12 months from last menstrual period, patient must have a serum estradiol \< or equal to 30 and an FSH level \> 40.
* Patients must not have had more than 1 prior chemotherapy regimen for metastatic disease and have fully recovered from any grade 2-4 toxicities related to chemotherapy. No concurrent chemotherapy is allowed while on protocol therapy.
* Patients may have had 1 prior hormonal therapy for metastatic disease. This includes: tamoxifen, fulvestrant, anastrozole, exemestane, aminoglutethimide, megace, and letrozole. Patients may have received tamoxifen or aromatase inhibitors in the adjuvant setting.
* Patients must not have had prior therapy with EGF receptor inhibitors.
* Previous but not concomitant therapy with trastuzumab (Herceptin) is allowed. Patients must not have received Herceptin within 4 weeks of initiation of protocol therapy.
* Patients must have an ECOG performance status of 0, 1, or 2.
* Patients must have adequate hematologic, hepatic, and renal function as defined by the following within 2 weeks of initiation of therapy:

* Absolute neutrophils \> or equal to 1,500/mm3 and platelets \> or equal to 100,000/mm3.
* Bilirubin \< than or equal to 1.5 upper limit of normal.
* SGOT and SGPT \< or equal to 2.5 upper limit of normal.
* Creatinine \< or equal to 1.5 upper limit of normal.
* INR, PTT and PT in the normal range.
* Must be 18 years of age or older.
* Patients must not have a history of central nervous system metastases or unevaluated CNS symptoms suggestive of possible brain metastases.
* Patients may receive concurrent radiation therapy to painful bone metastases or areas of impending bone fracture as long as radiation therapy is initiated prior to study entry and sites of evaluable disease outside the radiation port(s) are available for follow-up. Patients who have received prior radiotherapy must have recovered from toxicity induced by this treatment.
* Patients \< 55 years of age must not have received Luteinizing hormone releasing hormone (LHRH) antagonists within 3 months prior to protocol therapy.
* Patients must not suffer from medical or psychiatric conditions that would interfere with ability to provide informed consent, communicate side effects, or comply with protocol requirements including maintenance of a compliance/pill diary.
* Patients must be disease-free of prior invasive cancers for \> 5 years with the exception of basal or squamous cancer of the skin or cervical carcinoma in situ.
Minimum Eligible Age

18 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

Vanderbilt-Ingram Cancer Center

OTHER

Sponsor Role lead

Responsible Party

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Ingrid Mayer, MD

Assistant Professor of Medicine; Clinical Director, Breast Cancer Program; Medical Oncologist

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Ingrid Mayer, MD

Role: STUDY_CHAIR

Vanderbilt-Ingram Cancer Center

Locations

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Central Georgia Hematology/Oncology Associates, P.C.

Macon, Georgia, United States

Site Status

Jennie Stuart Medical Center

Hopkinsville, Kentucky, United States

Site Status

Purchase Cancer Group

Paducah, Kentucky, United States

Site Status

Memorial Health Care System

Chattanooga, Tennessee, United States

Site Status

The Jones Clinic - Germantown

Germantown, Tennessee, United States

Site Status

Jackson-Madison County Hospital

Jackson, Tennessee, United States

Site Status

Tennessee Cancer Specialists

Knoxville, Tennessee, United States

Site Status

Vanderbilt-Ingram Cancer Center - Cool Springs

Nashville, Tennessee, United States

Site Status

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, United States

Site Status

Countries

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United States

Other Identifiers

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VU-VICC-BRE-0303

Identifier Type: -

Identifier Source: secondary_id

VU-VICC-030592

Identifier Type: -

Identifier Source: secondary_id

GENENTECH-VU-VICC-BRE-0303

Identifier Type: -

Identifier Source: secondary_id

NOVARTIS-VU-VICC-BRE-0303

Identifier Type: -

Identifier Source: secondary_id

VICC BRE 0303

Identifier Type: -

Identifier Source: org_study_id

NCT00179296

Identifier Type: -

Identifier Source: nct_alias