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

NCT00611715 | Terminated Phase 2 Results DMC

• 5 other identifiers: VICC BRE 0303VU-VICC-BRE-0303VU-VICC-030592GENENTECH-VU-VICC-BRE-0303NOVARTIS-VU-VICC-BRE-0303
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 9

Brief Summary

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.

Conditions

Breast Cancer

Keywords

recurrent breast cancer; stage IV breast cancer

Outcome Measures

Primary Outcomes (1)

• Number of Patients With Pathological Complete Response.

  Per RECIST criteria v. 1.0: measurable lesions: complete response (CR) disappearance of target lesions, partial response (PR) \> 30% decrease in the sum of the longest diameter (LD) of target lesions, stable disease (SD) neither sufficient decrease nor increase of the sum of smallest sum of the LD of target lesions

  at 24 weeks

Secondary Outcomes (3)

• Median Time to Progression of Target Lesions

  Every 12 weeks from on-study to disease progression

• Number of Patients With Anti-tumor Activity: Complete Response (CR) and Partial Response (PR)

  at 24 weeks

• Number of Patients With Worst-grade Toxicities Per Grade

  at 24 weeks

Study Arms (2)

First line/hormone-therapy naive

EXPERIMENTAL

Drug: erlotinib hydrochloride; Drug: letrozole; Genetic: fluorescence in situ hybridization; Other: immunohistochemistry staining method; Other: laboratory biomarker analysis

Second-line/prev hormone-therapy tx

EXPERIMENTAL

Drug: erlotinib hydrochloride; Drug: letrozole; Genetic: fluorescence in situ hybridization; Other: immunohistochemistry staining method; Other: laboratory biomarker analysis

Interventions

erlotinib hydrochloride DRUG

OSI-774 150 mg/day

Also known as: Tarceva, OSI-774

First line/hormone-therapy naive; Second-line/prev hormone-therapy tx

letrozole DRUG

Letrozole 2.5 mg/day

Also known as: Femara

First line/hormone-therapy naive; Second-line/prev hormone-therapy tx

fluorescence in situ hybridization GENETIC

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

Also known as: None specified

First line/hormone-therapy naive; Second-line/prev hormone-therapy tx

immunohistochemistry staining method OTHER

to measure the epidermal growth factor receptors (EGFR)

Also known as: None specified

First line/hormone-therapy naive; Second-line/prev hormone-therapy tx

laboratory biomarker analysis OTHER

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

Also known as: none specified

First line/hormone-therapy naive; Second-line/prev hormone-therapy tx

Eligibility Criteria

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

* 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.

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Vanderbilt-Ingram Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (9)

Central Georgia Hematology/Oncology Associates, P.C.

Macon, Georgia, 31201, United States

Location

Jennie Stuart Medical Center

Hopkinsville, Kentucky, 42240, United States

Location

Purchase Cancer Group

Paducah, Kentucky, 42002, United States

Location

Memorial Health Care System

Chattanooga, Tennessee, 37404, United States

Location

The Jones Clinic - Germantown

Germantown, Tennessee, 38138, United States

Location

Jackson-Madison County Hospital

Jackson, Tennessee, 38301, United States

Location

Tennessee Cancer Specialists

Knoxville, Tennessee, 37909, United States

Location

Vanderbilt-Ingram Cancer Center - Cool Springs

Nashville, Tennessee, 37067, United States

Location

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, 37232-6838, United States

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Erlotinib Hydrochloride; Letrozole; In Situ Hybridization, Fluorescence; Immunohistochemistry

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Nitriles; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; In Situ Hybridization; Staining and Labeling; Histocytological Preparation Techniques; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Histological Techniques; Investigative Techniques; Cytogenetic Analysis; Genetic Techniques; Nucleic Acid Hybridization; Histocytochemistry; Immunologic Techniques

Limitations and Caveats

The total number of worst-grade toxicities will not match the total number of participants, as patients can have multiple events or no events.

Results Point of Contact

• Title: Ingrid Mayer, MD
• Organization: Vanderbilt-Ingram Cancer Center

ingrid.mayer@vanderbilt.edu

615-936-2033

Study Officials

• Ingrid Mayer, MD

  Vanderbilt-Ingram Cancer Center

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Medicine; Clinical Director, Breast Cancer Program; Medical Oncologist

Study Record Dates

• First Submitted: February 8, 2008
• First Posted: February 11, 2008
• Study Start: November 1, 2003
• Primary Completion: December 1, 2008
• Study Completion: December 1, 2008
• Last Updated: August 9, 2012
• Results First Posted: July 13, 2012

Record last verified: 2012-08

Locations

US (9)