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

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

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

Study Overview

• Status: Completed
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: letrozole

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 261
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Huntsville, Alabama, United States, 35805
      • Clearview Cancer Center
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • Hematology Oncology Services of Arkansas
  • California
    • Grass Valley, California, United States, 95945
      • Grass Valley Hematology Oncology
    • Palm Springs, California, United States, 92262
      • Aptium Oncology - Comprehensive Cancer Care of the Desert
    • Pleasant Hill, California, United States, 94523
      • Bay Area Cancer Research Group
  • Colorado
    • Fort Collins, Colorado, United States, 80528
      • Front Range Specialist
  • Florida
    • Boca Raton, Florida, United States, 33428
      • Lynn Cancer Center
    • Fort Myers, Florida, United States, 33916
      • Florida Cancer Specialists
    • Hollywood, Florida, United States, 33021
      • Memorial Cancer Center
    • West Palm Beach, Florida, United States, 33401
      • Palm Beach Cancer Specialists
  • Georgia
    • Athens, Georgia, United States, 30607
      • Northeast Georgia Cancer Care, LLC
    • Augusta, Georgia, United States, 30901
      • Augusta Oncology
    • Gainesville, Georgia, United States, 30501
      • Oncology Specialist of North Georgia
  • Illinois
    • Elk Grove Village, Illinois, United States, 60007
      • The Cancer Instiute at Alexian Brothers
    • Evanston, Illinois, United States, 60201
      • Evanston Northwestern Hospital
    • Skokie, Illinois, United States, 60076
      • Edward H. Kaplan MD & Associates - North Shore Cancer Research Associates
  • Kansas
    • Wichita, Kansas, United States, 67214
      • Cancer Care of Kansas
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • Kentuckiana Cancer Institute
  • Maine
    • Portland, Maine, United States, 04101
      • Mercy Hospital
  • Maryland
    • Baltimore, Maryland, United States, 21202
      • Mercey Hospital
    • Baltimore, Maryland, United States, 21237
      • Maryland Hematology Oncology Associates, PA
    • Bethesda, Maryland, United States, 20817
      • Suburban Hospital Cancer Program
  • Michigan
    • Lambertville, Michigan, United States, 48144
      • Hematology Oncology Asssociates of Ohio & Michigan
  • Missouri
    • Saint Louis, Missouri, United States, 63141
      • Center for Cancer Care and Research
    • Saint Louis, Missouri, United States, 63414
      • Ballas Cancer Center, LLC DBA - St Louis
  • Nebraska
    • Lincoln, Nebraska, United States, 68516
      • Southeast Nebraska Hematology & Oncology Consultants
  • New Jersey
    • Elizabeth, New Jersey, United States, 07207
      • Trinitas Comprehensive Cancer Center
    • Morristown, New Jersey, United States, 07962
      • Hematology-Oncology Assoc of Northern New Jersey
    • Somerville, New Jersey, United States, 08876
      • Somerset Hematology & Oncology
    • Voorhees, New Jersey, United States, 08043
      • Cooper University Hospital
  • New York
    • Binghamton, New York, United States, 13905
      • Broom Oncology
  • North Carolina
    • Asheville, North Carolina, United States, 28801
      • Cancer Care of W. NC
    • Washington, North Carolina, United States, 27889
      • Marion L. Shepard Cancer Center
  • Ohio
    • Akron, Ohio, United States, 44304
      • Summa Health System
    • Medina, Ohio, United States, 44256
      • Mukesh Bhatt, MD, INC.
  • Pennsylvania
    • West Reading, Pennsylvania, United States, 19611
      • Berks Hematology Oncology
  • South Carolina
    • Columbia, South Carolina, United States, 29210
      • South Carolina Oncology Associates
  • Tennessee
    • Memphis, Tennessee, United States, 38138
      • The West Clinic
    • Nashville, Tennessee, United States, 37203
      • Tenessee Oncology
  • Texas
    • Corpus Christi, Texas, United States, 78404
      • Coastal Bend Cancer Center
    • Dallas, Texas, United States, 75230
      • Center for Oncology Research and Treatment
  • Utah
    • American Fork, Utah, United States, 84003
      • Central Utah Clinic
    • Ogden, Utah, United States, 84403
      • Northern Utah Associates
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Medical Oncology & Hematology Associates of Northern Virginia
    • Harrisonburg, Virginia, United States, 22801
      • Rockingham Memorial Hospital Regional Cancer Center
    • Newport News, Virginia, United States, 23601
      • Peninsula Cancer Center
  • Wisconsin
    • Green Bay, Wisconsin, United States, 54301
      • Green Bay Oncologist, St Vincent Hospital
    • Wauwatosa, Wisconsin, United States, 53226
      • Oncology Alliance

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Letrozole; Participants received 2.5 milligram (mg) of Letrozole tablets orally once daily (QD) for a period of 24 weeks.	Drug: letrozole; 2.5 mg daily by mouth for 6 months; Other Names: Femara

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)
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)
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)
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)
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)

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Publications and helpful links

Helpful Links

• Results for CFEM345DUS59 from the Novartis Clinical Trials Results Database

Study record dates

Study Major Dates

• Study Start: March 1, 2008
• Primary Completion (Actual): June 1, 2009
• Study Completion (Actual): June 1, 2009

Study Registration Dates

• First Submitted: May 29, 2008
• First Submitted That Met QC Criteria: June 2, 2008
• First Posted (Estimate): June 3, 2008

Study Record Updates

• Last Update Posted (Actual): June 9, 2021
• Last Update Submitted That Met QC Criteria: May 23, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Keywords: breast cancer; letrozole; adjuvant treatment in post menopausal women; arthralgia-myalgia
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Hormone Antagonists; Aromatase Inhibitors; Steroid Synthesis Inhibitors; Estrogen Antagonists; Letrozole
• Other Study ID Numbers: CFEM345DUS59