A Randomized, Controlled Trial of High Dose vs. Standard Dose Vitamin D for Aromatase-Inhibitor Induced Arthralgia in Breast Cancer Survivors Protocol Number H-33261 Protocol Chair Mothaffar Rimawi, M.D. Baylor College of Medicine One Baylor Plaza BCM 600 Houston, TX 77030 Phone: (713) 798-1311 Fax: (713) 798-8884 Email: [email protected] IND Number: 120053 NCT Number: NCT01988090 Additional Sites Washington University Site PI: Foluso Ademuyiwa, MD High Dose Vitamin D for AIA Rimawi A Randomized, Controlled Trial of High Dose vs. Standard Dose Vitamin D for Aromatase- Inhibitor Induced Arthralgia in Breast Cancer Survivors - Protocol Revision Record – Original Protocol: April 18, 2013 Revision 1: July 22, 2013 Revision 2: September 3, 2013 Revision 3: November 18, 2013 Revision 4: July 14, 2015 Vitamin D for AIA TABLE OF CONTENTS 1. BACKGROUND ............................................................................................................................................ 5 1.1 TREATMENT OF HORMONE RECEPTOR POSITIVE BREAST CANCER..................................................................... 5 1.2 MUSCULOSKELETAL SIDE EFFECTS OF HORMONAL THERAPY ........................................................................... 6 1.3 MANAGEMENT OF AIA ......................................................................................................................... 8 1.4 VITAMIN D AND BREAST CANCER............................................................................................................. 9 1.5 VITAMIN D BACKGROUND ..................................................................................................................... 9 1.6 STUDY RATIONALE ............................................................................................................................. 10 2. OBJECTIVES ........................................................................................................................................... 11 2.1 PRIMARY OBJECTIVE ........................................................................................................................... 11 2.2 SECONDARY OBJECTIVES ...................................................................................................................... 12 2.3 EXPLORATORY OBJECTIVE .................................................................................................................... 12 3. STUDY DESIGN/SUMMARY ................................................................................................................... 12 SCHEMA ........................................................................................................................................................ 14 4. PARTICIPANT SELECTION ...................................................................................................................... 15 4.1 INCLUSION CRITERIA ........................................................................................................................... 15 4.2 EXCLUSION CRITERIA .......................................................................................................................... 15 4.3 INCLUSION OF UNDERREPRESENTED POPULATIONS ..................................................................................... 16 5. REGISTRATION PROCEDURES ................................................................................................................ 16 5.1 GUIDELINES ...................................................................................................................................... 16 5.2 ELIGIBILITY EXCEPTIONS ....................................................................................................................... 17 6. STUDY PROCEDURES ............................................................................................................................. 17 6.1 SCREENING AND BASELINE ASSESSMENTS ................................................................................................. 17 6.2 FOLLOW-UP AT WEEK 4 ...................................................................................................................... 18 6.3 FOLLOW-UP AT WEEK 12 .................................................................................................................... 18 6.4 FOLLOW UP AT WEEKS 24 AND 36......................................................................................................... 19 6.5 FOLLOW UP AT WEEK 52, AND END OF TREATMENT VISIT ............................................................................ 19 6.6 SAFETY FOLLOW-UP ........................................................................................................................... 20 6.7 UPON COMPLETION OF THE THERAPEUTIC REGIMEN, SUBJECTS WILL BE FOLLOWED FOR ADVERSE EVENTS FOR A PERIOD OF 30 DAYS AFTER THE LAST DOSE OF VITAMIN D ON STUDY. PATIENTS WITH ABNORMAL LABORATORY OR CLINICAL FINDINGS THAT ARE BELIEVED TO BE TREATMENT RELATED WILL BE FOLLOWED UNTIL THE CONDITION RESOLVES, STABILIZES, OR UNTIL THE LABORATORY VALUES ARE NO LONGER CONSIDERED CLINICALLY SIGNIFICANT. NEW ADVERSE EVENTS THAT OCCUR DURING THE 30 DAY FOLLOW-UP PERIOD WILL ONLY BE RECORDED IF THE INVESTIGATOR BELIEVES THERE IS A REASONABLE POSSIBILITY THAT THE ADVERSE EVENT IS DRUG-RELATED. THE SAFETY FOLLOW-UP MAY BE CONDUCTED BY A PHONE VISIT OR A CLINIC VISIT; IF CLINICALLY INDICATED, A CLINIC VISIT SHOULD BE PERFORMED ALONG WITH RELEVANT LAB WORK. PER STANDARD OF CARE AND NCCN GUIDELINES, BONE DENSITY SCAN WILL BE REPEATED, AT THE TREATING PHYSICIAN’S DISCRETION, EVERY 1-2 YEARS WHILE THE PATIENT IS ON AI THERAPY. PER NNCN GUIDELINES, PATIENT WILL HAVE DEXA SCAN EVERY 2 YEARS WHILE ON AI THERAPY, OR EVERY YEAR IF ACCELERATED BONE LOSS IS SUSPECTED, OR THERAPEUTIC INTERVENTION APPLIED. DURATION OF FOLLOW-UP 20 3 Vitamin D for AIA 6.8 ON STUDY ASSESSMENTS AND PROCEDURES ............................................................................................ 20 6.9 AGENT ADMINISTRATION ..................................................................................................................... 21 6.10 COMPLIANCE .................................................................................................................................... 23 6.11 PROHIBITED THERAPIES ....................................................................................................................... 23 6.12 DISCONTINUATION OF TREATMENT ........................................................................................................ 23 6.13 WITHDRAWAL FROM STUDY ................................................................................................................. 24 6.14 CRITERIA FOR REMOVAL FROM THE STUDY ............................................................................................... 24 6.15 SUBJECT COMPENSATION ..................................................................................................................... 25 7. DRUG FORMULATION/STORAGE/SUPPLY ............................................................................................. 25 7.1 VITAMIN D3, 5000 IU ....................................................................................................................... 25 7.2 VITAMIN D3, 2000 IU ....................................................................................................................... 25 7.3 CALTRATE-D, CALCIUM 600 MG & VITAMIN D3 800 IU ............................................................................ 25 7.4 DRUG ACCOUNTABILITY ...................................................................................................................... 25 8. DOSING DELAYS/DOSE MODIFICATIONS ............................................................................................... 26 8.1 DOSE MODIFICATIONS/DELAYS ............................................................................................................. 26 8.2 SPECIAL CONSIDERATIONS.................................................................................................................... 26 9. ADVERSE EVENTS & SAFETY MONITORING ........................................................................................... 26 9.1 GENERAL ......................................................................................................................................... 27 9.2 DEFINITIONS ..................................................................................................................................... 27 9.3 ANTICIPATED TOXICITIES ...................................................................................................................... 29 9.4 TOXICITY MANAGEMENT ..................................................................................................................... 29 9.5 ADVERSE EVENT FOLLOW-UP ................................................................................................................ 30 9.6 REPORTING PROCEDURES .................................................................................................................... 30 10. CORRELATIVE/SPECIAL STUDIES ....................................................................................................... 32 10.1 GRIP STRENGTH ................................................................................................................................ 32 11. SPECIMEN BANKING ........................................................................................................................