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

Phase 2
18 Years
Not Enrolling
Breast Cancer

Thank you

Trial Information

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



- 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


- 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

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

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.

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

- 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

- 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.

Type of Study:


Study Design:

Allocation: Non-Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Number of Patients With Pathological Complete Response.

Outcome Description:

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

Outcome Time Frame:

at 24 weeks

Safety Issue:


Principal Investigator

Ingrid Mayer, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Vanderbilt-Ingram Cancer Center


United States: Food and Drug Administration

Study ID:




Start Date:

November 2003

Completion Date:

December 2008

Related Keywords:

  • Breast Cancer
  • recurrent breast cancer
  • stage IV breast cancer
  • Breast Neoplasms



Vanderbilt-Ingram Cancer Center Nashville, Tennessee  37232-6838
Memorial Health Care System Chattanooga, Tennessee  37404
Jackson-Madison County Hospital Jackson, Tennessee  38301
Tennessee Cancer Specialists Knoxville, Tennessee  37920
Vanderbilt-Ingram Cancer Center - Cool Springs Nashville, Tennessee  37064
Jennie Stuart Medical Center Hopkinsville, Kentucky  42240
Central Georgia Hematology/Oncology Associates, P.C. Macon, Georgia  31201
Purchase Cancer Group Paducah, Kentucky  42002
The Jones Clinic - Germantown Germantown, Tennessee  38138