Rheumatological Evaluation of Anastrozole and Letrozole as Adjuvant Treatment in Post-menopausal Women With Breast Cancer

Breast Cancer Clinical Trial

— REAL  

Official title:

Open-label, Single-arm, Multicenter Study to Evaluate the Rheumatological Tolerability of Letrozole as an Adjuvant Breast Cancer Treatment in Postmenopausal Women Who Are Intolerant and Discontinue Anastrozole Due to Grade 2-3 Arthralgia-myalgia

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00688909
• Other study ID #: CFEM345DUS59
• Status: Completed
• Phase: Phase 4
• Start date: March 2008
• Est. completion date: June 2009

Study information

• Verified date: May 2021
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study will evaluate whether patients who are intolerant and discontinue anastrozole due to grade 2-3 arthralgia-myalgia have a decrease in rheumatological symptoms while taking letrozole

Description:

This is a multi-center prospective non-randomized single arm, open label trial in postmenopausal HR positive early breast cancer patients who experience grade 2-3 arthralgia-myalgia while on anastrozole, resulting in the discontinuation of anastrozole. After a 2-3 week period without any aromatase inhibitor treatment, eligible patients will initiate letrozole treatment at a dose of 2.5mg per day for a duration of 24 weeks. If a patient has breast cancer recurrence or is intolerant to letrozole during the 24 week period, the drug will be discontinued.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 261
• Est. completion date: June 2009
• Est. primary completion date: June 2009
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 50 Years and older

Eligibility

Inclusion Criteria:

1. Postmenopausal women with HR+ early stage breast cancer at the time of initial diagnosis. For study purposes, postmenopausal is defined as:

• Age = 50 y and amenorrheic for 12 or more months.

• Age = 50 y and amenorrheic for 3 or more months after receiving adjuvant chemotherapy.

• Age < 50 y and amenorrheic for 12 or more months.

• Prior bilateral oophorectomy.

• Prior hysterectomy and has postmenopausal levels of FSH, LH, and estradiol as per local institutional standards.

• Age > 55 y and prior hysterectomy.

2. Patients who are intolerant and discontinue anastrozole 2-3 weeks prior to study entry when given as adjuvant treatment for HR+ early stage breast cancer due to grade 2-3 (NCI-CTCAE V3) arthralgia-myalgia.

3. Hormone receptor-positive tumors as defined by institutional standards.

4. ECOG performance status of 0, 1, or 2

5. Consent to participate in the trial. -

Exclusion Criteria:

1. Postmenopausal women with HR+ metastatic or locally relapsed breast cancer excluding chest wall recurrence with no evidence of systemic disease.

2. Recent history of pain associated with non-traumatic bone fracture.

3. Pain requiring chronic use of analgesics (due to any reason).

4. History of rheumatological disease except osteoarthritis.

5. Prior hormonal therapy with AIs other than anastrozole.

6. Systemic hormone replacement therapy (HRT) less than 4 weeks before study entry other than Estring®, Vagifem® or low dose estrogen vaginal cream.

7. Concomitant disease which significantly affects quality of life.

8. Patient unable to complete self administered questionnaire.

9. Patients unable to sign consent form.

Other protocol-defined inclusion/exclusion criteria may apply

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Drug:
• letrozole
2.5 mg daily by mouth for 6 months

Locations

Country	Name	City	State
United States	Summa Health System	Akron	Ohio
United States	Central Utah Clinic	American Fork	Utah
United States	Cancer Care of W. NC	Asheville	North Carolina
United States	Northeast Georgia Cancer Care, LLC	Athens	Georgia
United States	Augusta Oncology	Augusta	Georgia
United States	Maryland Hematology Oncology Associates, PA	Baltimore	Maryland
United States	Mercey Hospital	Baltimore	Maryland
United States	Suburban Hospital Cancer Program	Bethesda	Maryland
United States	Broom Oncology	Binghamton	New York
United States	Lynn Cancer Center	Boca Raton	Florida
United States	South Carolina Oncology Associates	Columbia	South Carolina
United States	Coastal Bend Cancer Center	Corpus Christi	Texas
United States	Center for Oncology Research and Treatment	Dallas	Texas
United States	Trinitas Comprehensive Cancer Center	Elizabeth	New Jersey
United States	The Cancer Instiute at Alexian Brothers	Elk Grove Village	Illinois
United States	Evanston Northwestern Hospital	Evanston	Illinois
United States	Medical Oncology & Hematology Associates of Northern Virginia	Fairfax	Virginia
United States	Front Range Specialist	Fort Collins	Colorado
United States	Florida Cancer Specialists	Fort Myers	Florida
United States	Oncology Specialist of North Georgia	Gainesville	Georgia
United States	Grass Valley Hematology Oncology	Grass Valley	California
United States	Green Bay Oncologist, St Vincent Hospital	Green Bay	Wisconsin
United States	Rockingham Memorial Hospital Regional Cancer Center	Harrisonburg	Virginia
United States	Memorial Cancer Center	Hollywood	Florida
United States	Clearview Cancer Center	Huntsville	Alabama
United States	Hematology Oncology Asssociates of Ohio & Michigan	Lambertville	Michigan
United States	Southeast Nebraska Hematology & Oncology Consultants	Lincoln	Nebraska
United States	Hematology Oncology Services of Arkansas	Little Rock	Arkansas
United States	Kentuckiana Cancer Institute	Louisville	Kentucky
United States	Mukesh Bhatt, MD, INC.	Medina	Ohio
United States	The West Clinic	Memphis	Tennessee
United States	Hematology-Oncology Assoc of Northern New Jersey	Morristown	New Jersey
United States	Tenessee Oncology	Nashville	Tennessee
United States	Peninsula Cancer Center	Newport News	Virginia
United States	Northern Utah Associates	Ogden	Utah
United States	Aptium Oncology - Comprehensive Cancer Care of the Desert	Palm Springs	California
United States	Bay Area Cancer Research Group	Pleasant Hill	California
United States	Mercy Hospital	Portland	Maine
United States	Ballas Cancer Center, LLC DBA - St Louis	Saint Louis	Missouri
United States	Center for Cancer Care and Research	Saint Louis	Missouri
United States	Edward H. Kaplan MD & Associates - North Shore Cancer Research Associates	Skokie	Illinois
United States	Somerset Hematology & Oncology	Somerville	New Jersey
United States	Cooper University Hospital	Voorhees	New Jersey
United States	Marion L. Shepard Cancer Center	Washington	North Carolina
United States	Oncology Alliance	Wauwatosa	Wisconsin
United States	Palm Beach Cancer Specialists	West Palm Beach	Florida
United States	Berks Hematology Oncology	West Reading	Pennsylvania
United States	Cancer Care of Kansas	Wichita	Kansas

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants Discontinuing Due to Grade 2 or Higher Arthralgia-myalgia.	The arthralgia status and the myalgia status were separately graded at Baseline (V1), Week 12 (V3) , and Week 24/EOS (V4). The grades of 0 for no pain, 1 for mild pain, 2 for moderate pain, 3 for severe pain, and 4 for disabling pain were used.	End of Study (24 weeks)
Secondary	Time to Discontinuation Due to Grade 2 or Higher Arthralgia- Myalgia.	For patients who discontinued from the study due to either grade 2 or higher arthralgia-myalgia, the time to discontinuation was calculated as the duration between the Visit 1 date and the last dose date. If the last dose date was missing, the EOS date was used.	End of Study (24 weeks)
Secondary	Percentage of Participants Discontinuing, Irrespective of Cause	The percentage of patients who discontinued from the study irrespective of the reasons.	End of Study (24 weeks)
Secondary	Change in Brief Pain Inventory (BPI) Composite Score	The BPI is a pain assessment tool for use with cancer patients. The BPI measures both the intensity of pain (sensory dimension) and interference of pain in the patient's life (reactive dimension). It also queries the patient about pain relief, pain quality, and patient perception of the cause of pain. The BPI composite score was calculated based on questions 3 to 6 of the BPI Questionnaire (short form). First each question was scored from 0 (no pain) to 10 (pain as bad as you can imagine) and circled on the CRF. Then a composite score was calculated as the mean of the scores. If any answer was missing, the composite score was set to missing. Change in BPI composite score indicates the change from baseline at week 24.	Baseline, 24 weeks (End of Study)
Secondary	Change in Disability Index as Assessed by Health Assessment Questionnaire (HAQ)	The HAQ is a validated, patient-oriented outcome assessment instrument. The short version '2 page HAQ' was used. It contains the HAQ Disability Index (HAQ-DI), the HAQ visual analog scale (VAS) for pain and the VAS patient global health scale. The Stanford HAQ 20-item disability scale was utilized for scoring of the Disability Index. The items were first scored within each category with values 0 to 3 (0 = Without any difficulty, 1 = With some difficulty, 2 = With much difficulty, 3 = Unable to do). The score for the disability index was the mean of the eight category scores. If more than 2 of the 8 categories, or >25%, were missing, the scale was not scored. If =2 of the categories were missing, the sum of the categories was divided by the number of answered categories. Change in Disability Index indicates the change from baseline at week 24.	Baseline, Visit 1(24 weeks = End of Study)
Secondary	Change in Pain as Assessed by Visual Analog Scale (VAS) Scale of the Health Assessment Questionnaire (HAQ)	The HAQ is a validated, patient-oriented outcome assessment instrument. The short version '2 page HAQ' was used. It contains the HAQ Disability Index (HAQ-DI), the HAQ visual analog scale (VAS) for pain and the VAS patient global health scale. The VAS is a tool used to help a person rate the intensity of certain sensations and feelings, such as pain. The visual analog scale for pain is a straight line with one end meaning no pain and the other end meaning the worst pain imaginable. For pain intensity, the scale is most commonly anchored by "no pain" (score of 0) and "pain as bad as it could be" or "worst imaginable pain" (score of 100 [100-mm scale]). A higher score indicates greater pain intensity. Change in pain as assessed by VAS indicates the change from baseline at week 24.	Baseline, Visit 1 (24 weeks = End of Study)

External Links

•   Results for CFEM345DUS59 from the Novartis Clinical Trials Results Database