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Intermittent Letrozole Therapy in Postmenopausal Women With Metastatic Breast Cancer

Primary Purpose

Breast Cancer

Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Letrozole
Sponsored by
Massachusetts General Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Breast Cancer focused on measuring aromatase inhibitor, CA 15-3, Hormone receptor positive

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

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

Sites / Locations

  • Dana-Farber Cancer Institute
  • Massachusetts General Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Intermittent letrozole therapy

Arm Description

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.

Outcomes

Primary Outcome Measures

Number of Patients With Decline in Serum CA 15-3 (Carcinoma Antigen 15-3)
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.

Secondary Outcome Measures

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

Full Information

First Posted
October 24, 2007
Last Updated
February 1, 2017
Sponsor
Massachusetts General Hospital
Collaborators
Dana-Farber Cancer Institute, Novartis
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1. Study Identification

Unique Protocol Identification Number
NCT00549822
Brief Title
Intermittent Letrozole Therapy in Postmenopausal Women With Metastatic Breast Cancer
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
February 2017
Overall Recruitment Status
Terminated
Why Stopped
Slow Accrual
Study Start Date
October 2007 (Actual)
Primary Completion Date
May 2010 (Actual)
Study Completion Date
September 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Massachusetts General Hospital
Collaborators
Dana-Farber Cancer Institute, Novartis

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Breast Cancer
Keywords
aromatase inhibitor, CA 15-3, Hormone receptor positive

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
3 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Intermittent letrozole therapy
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Letrozole
Other Intervention Name(s)
Femara
Intervention Description
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.
Primary Outcome Measure Information:
Title
Number of Patients With Decline in Serum CA 15-3 (Carcinoma Antigen 15-3)
Description
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.
Time Frame
3 years
Secondary Outcome Measure Information:
Title
Median Time to Disease Progression With Intermittent Letrozole.
Description
The median time to disease progression as determined by RECIST (Response Evaluation Criteria In Solid Tumors).
Time Frame
3 years
Title
Serum HER-2/Neu Levels and Serum/Plasma Angiogenic Mediators
Description
Measurements for the serum HER-2/neu (human epidermal growth factor receptor 2) levels and serum/plasma angiogenic mediators
Time Frame
2 years

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Paul Goss, MD, PhD
Organizational Affiliation
Massachusetts General Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Dana-Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No

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Intermittent Letrozole Therapy in Postmenopausal Women With Metastatic Breast Cancer

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