Intermittent Letrozole Therapy in Postmenopausal Women With Metastatic Breast Cancer

February 1, 2017 updated by: Paul Goss, MD, PhD, Massachusetts General Hospital

A Phase II Clinical Trial of Intermittent Letrozole Therapy in Postmenopausal Women With CA 15-3 Positive (Carcinoma Antigen 15-3), Hormone Receptor Positive, Metastatic Breast Cancer

The purpose of this research study is to study the effects of using aromatase inhibitor (AI) therapy intermittently on participants with breast cancer. AIs are a class of drugs used to treat breast cancer in postmenopausal women. They work by decreasing the level of estrogen, which is believed to stimulate the growth of tumor tissue. Breast cancer that progresses despite therapy with an AI is thought to have become resistant to AI therapy. There is scientific evidence to suggest that resistant breast cancer cells learn to grow at the very low levels of estrogen present on AI therapy, and that increasing estrogen levels even slightly by stopping AI therapy may inhibit the breast cancer cells.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

  • This study involves treating participants with intermittent AI therapy. The AI will be stopped at the time they enter the study. We plan on monitoring a marker in the participants blood called CA 15-3 (or CA 27.29) every 4 weeks to help us make a decision of when to re-start treatment with letrozole (femara). This marker is known to rise when disease is progressing and drop when the disease is responding to treatment. We will be stopping and re-starting therapy based on the changes of CA 15-3 in the participants blood.
  • In addition to bloodwork, the following tests and procedures will be performed on a monthly basis: medical history; physical examination and performance status.
  • Every 8 weeks the following will be performed: Tumor assessment by physical exam (if possible); Chest x-ray or CT scan or chest; CT scans of abdomen and pelvis; and bone scan.

Study Type

Interventional

Enrollment (Actual)

3

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Massachusetts
      • Boston, Massachusetts, United States, 02115
        • Dana-Farber Cancer Institute
      • Boston, Massachusetts, United States, 02215
        • Massachusetts General Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  • Female
  • 18 years of age or older
  • Postmenopausal
  • Histologically or cytologically confirmed adenocarcinoma of the breast with locally advanced or metastatic disease this is not considered amenable to curative treatment with elevation of CA 15-3 documented at the time of diagnosis of metastatic disease and prior to initiation of letrozole or anastrozole therapy
  • Current letrozole or anastrozole monotherapy with a documented CA 15-3 level that has decreased by at least 50% of the patients baseline
  • Letrozole or anastrozole must be discontinued at the time of study enrollment
  • Evidence of hormone sensitivity of primary or secondary tissue.
  • Measurable or nonmeasurable (but evaluable-defined as nontarget lesions) disease according to modified RECIST
  • Prior antiestrogen therapies including tamoxifen, steroidal AIs, nonsteroidal AIs, or fulvestrant in the adjuvant setting is allowed provided the patient is currently on letrozole or anastrozole monotherapy as first-line therapy for metastatic disease
  • Life expectancy of greater than 3 months
  • ECOG (Eastern Cooperative Oncology Group) Performance Status of 0,1, or 2
  • Normal organ and marrow function as outlined in protocol

Exclusion Criteria:

  • Premenopausal
  • Trastuzumab or biologic therapy within 2 weeks
  • Prior or planned radiation therapy to a site of evaluable disease in the event that the site is the only site of evaluable disease
  • Concomitant anticancer treatments including trastuzumab, chemotherapy, or other biologic agents other than letrozole or anastrozole therapy
  • Chronic bisphosphonates for hypercalcemia or prevention of bone metastases.
  • Treatment with non-approved or investigational agent within 2 weeks before study entry
  • Presence of life-threatening metastatic disease, defined as extensive hepatic involvement, or past or present brain or leptomeningeal involvement, or symptomatic pulmonary lymphangitic spread
  • Patients who are highly symptomatic from their breast cancer, or who require urgent palliative chemotherapy, as decided by their treating physician
  • Previous or current systemic malignancy within the past five years, except for contralateral breast carcinoma, in situ carcinoma of the cervix treated by cone biopsy, or adequately treated basal or squamous cell carcinoma of the skin.
  • Any severe concomitant condition believed to render subject undesirable for participation

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Intermittent letrozole therapy
Letrozole 2.5 mg administered by mouth daily during each 28 day treatment cycle. Treatment is intermittent with possible breaks between each 28 day treatment cycle based on CA 15-3 or CA 27.29 levels. Letrozole is administered until the participant has disease progression as determined by RECIST (Response Evaluation Criteria In Solid Tumors), experiences severe side effects, or decides to stop treatment.
Drug: Letrozole
Treatment is intermittent with possible breaks between each 28 day treatment cycle if CA 15-3 or CA 27.29 level that has decreased by at least 50% of that individual patient's baseline or peak level on firstline letrozole or anastrozole therapy or has decreased into the normal reference range per institutional parameters. Letrozole or anastrozole therapy will be interrupted until CA 15-3 or CA 27.29 levels rise by at least 25% above trough CA 15-3 or CA 27.29 level. If the trough level is in the normal reference range then the CA 15-3 or CA 27.29 must rise into the normal reference range.
Other Names:
  • Femara

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Patients With Decline in Serum CA 15-3 (Carcinoma Antigen 15-3)
Time Frame: 3 years
The Number of patients that have have a response of a decrease in CA 15-3 or CA 27.29 levels by at least 50% of that individual patient's baseline or peak level after re-introducing Letrozole therapy following a break in therapy as described in the intervention.
3 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Median Time to Disease Progression With Intermittent Letrozole.
Time Frame: 3 years
The median time to disease progression as determined by RECIST (Response Evaluation Criteria In Solid Tumors).
3 years
Serum HER-2/Neu Levels and Serum/Plasma Angiogenic Mediators
Time Frame: 2 years
Measurements for the serum HER-2/neu (human epidermal growth factor receptor 2) levels and serum/plasma angiogenic mediators
2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Massachusetts General Hospital

Collaborators

Novartis
Dana-Farber Cancer Institute

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

October 1, 2007

Primary Completion (ACTUAL)

May 1, 2010

Study Completion (ACTUAL)

September 1, 2013

Study Registration Dates

First Submitted

October 24, 2007

First Submitted That Met QC Criteria

October 24, 2007

First Posted (ESTIMATE)

October 26, 2007

Study Record Updates

Last Update Posted (ACTUAL)

March 22, 2017

Last Update Submitted That Met QC Criteria

February 1, 2017

Last Verified

February 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 07-109

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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