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

A Phase II Trial of Letrozole Plus OSI-774 (Tarceva) in Post-menopausal Women With ER and/or PR-Positive Metastatic Breast Cancer

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.

Study Overview

• Status: Terminated
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: erlotinib hydrochloride; Drug: letrozole; Genetic: fluorescence in situ hybridization; Other: immunohistochemistry staining method; Other: laboratory biomarker analysis

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 48
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Georgia
    • Macon, Georgia, United States, 31201
      • Central Georgia Hematology/Oncology Associates, P.C.
  • Kentucky
    • Hopkinsville, Kentucky, United States, 42240
      • Jennie Stuart Medical Center
    • Paducah, Kentucky, United States, 42002
      • Purchase Cancer Group
  • Tennessee
    • Chattanooga, Tennessee, United States, 37404
      • Memorial Health Care System
    • Germantown, Tennessee, United States, 38138
      • The Jones Clinic - Germantown
    • Jackson, Tennessee, United States, 38301
      • Jackson-Madison County Hospital
    • Knoxville, Tennessee, United States, 37909
      • Tennessee Cancer Specialists
    • Nashville, Tennessee, United States, 37232-6838
      • Vanderbilt-Ingram Cancer Center
    • Nashville, Tennessee, United States, 37067
      • Vanderbilt-Ingram Cancer Center - Cool Springs

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: First line/hormone-therapy naive	Drug: erlotinib hydrochloride; OSI-774 150 mg/day; Other Names: Tarceva, OSI-774; Drug: letrozole; Letrozole 2.5 mg/day; Other Names: Femara; Genetic: fluorescence in situ hybridization; To determine HER2 gene amplification or excess copies of the HER2 gene; Other Names: None specified; Other: immunohistochemistry staining method; to measure the epidermal growth factor receptors (EGFR); Other Names: None specified; Other: laboratory biomarker analysis; To determine if specific biomarkers exhibit a longer time to tumor progression after treatment with the study drugs; Other Names: none specified
Experimental: Second-line/prev hormone-therapy tx	Drug: erlotinib hydrochloride; OSI-774 150 mg/day; Other Names: Tarceva, OSI-774; Drug: letrozole; Letrozole 2.5 mg/day; Other Names: Femara; Genetic: fluorescence in situ hybridization; To determine HER2 gene amplification or excess copies of the HER2 gene; Other Names: None specified; Other: immunohistochemistry staining method; to measure the epidermal growth factor receptors (EGFR); Other Names: None specified; Other: laboratory biomarker analysis; To determine if specific biomarkers exhibit a longer time to tumor progression after treatment with the study drugs; Other Names: none specified

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Median Time to Progression of Target Lesions	Time frame from study entry till discontinuation of treatment due to disease progression. Progression of target lesions is measured by 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, progressive disease (PD) > 20% increase in the sum of the LD of target lesions or appearance of new lesions, stable disease (SD) neither sufficient decrease nor increase of the sum of smallest sum of the LD 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)	Per RECIST criteria v. 1.0: measurable lesions: complete response (CR) disappearance of target lesions and partial response (PR) > 30% decrease in the sum of the longest diameter (LD) of target lesions.	at 24 weeks
Number of Patients With Worst-grade Toxicities Per Grade	Number of patients with worst-grade toxicities following NCI Common Toxicity Criteria: 1 = mild, 2 = moderate, 3 = severe, 4 = life-threatening, disabling, 5 = death	at 24 weeks

Collaborators and Investigators

• Sponsor: Vanderbilt-Ingram Cancer Center
• Collaborators: National Cancer Institute (NCI)

Study record dates

Study Major Dates

• Study Start: November 1, 2003
• Primary Completion (Actual): December 1, 2008
• Study Completion (Actual): December 1, 2008

Study Registration Dates

• First Submitted: February 8, 2008
• First Submitted That Met QC Criteria: February 8, 2008
• First Posted (Estimate): February 11, 2008

Study Record Updates

• Last Update Posted (Estimate): August 9, 2012
• Last Update Submitted That Met QC Criteria: August 3, 2012
• Last Verified: August 1, 2012

More Information

Terms related to this study

• Keywords: stage IV breast cancer; recurrent breast cancer
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Protein Kinase Inhibitors; Hormone Antagonists; Aromatase Inhibitors; Steroid Synthesis Inhibitors; Estrogen Antagonists; Erlotinib Hydrochloride; Letrozole
• Other Study ID Numbers: VICC BRE 0303; VU-VICC-BRE-0303; VU-VICC-030592; GENENTECH-VU-VICC-BRE-0303; NOVARTIS-VU-VICC-BRE-0303