Intermittent Letrozole Therapy in Postmenopausal Women With Metastatic Breast Cancer

NCT00549822 | Terminated Phase 2 Results DMC

• 1 other identifier: 07-109
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 2

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.

Conditions

Breast Cancer

Keywords

aromatase inhibitor; CA 15-3; Hormone receptor positive

Outcome Measures

Primary Outcomes (1)

• 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.

  3 years

Secondary Outcomes (2)

• Median Time to Disease Progression With Intermittent Letrozole.

  3 years

• Serum HER-2/Neu Levels and Serum/Plasma Angiogenic Mediators

  2 years

Study Arms (1)

Intermittent letrozole therapy

EXPERIMENTAL

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

Interventions

Letrozole DRUG

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.

Also known as: Femara

Intermittent letrozole therapy

Eligibility Criteria

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

You may qualify if:

• Female
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• Dana-Farber Cancer Institute: collaborator
• Novartis: collaborator

Study Sites (2)

Dana-Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02215, United States

Location

MeSH Terms

Conditions

Breast Neoplasms; Medullary cystic kidney disease 1

Interventions

Letrozole

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Nitriles; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Limitations and Caveats

The study closed prematurely before the planned enrollment of 20 patients due to poor patient accrual. The patient population was highly selected, were likely to have had disease with an indolent natural history.

Results Point of Contact

• Title: Dr. Paul Goss
• Organization: Massachusetts General Hospital

pgoss@mgh.harvard.edu

617-724-3118

Study Officials

• Paul Goss, MD, PhD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine, Harvard Medical School

Study Record Dates

• First Submitted: October 24, 2007
• First Posted: October 26, 2007
• Study Start: October 1, 2007
• Primary Completion: May 1, 2010
• Study Completion: September 1, 2013
• Last Updated: March 22, 2017
• Results First Posted: March 22, 2017

Record last verified: 2017-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)