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A221102 Randomized Double-Blind Placebo Controlled Study Of A221102 ALLIANCE FOR CLINICAL TRIALS IN ONCOLOGY Randomized Double-Blind Placebo Controlled Study of Testosterone in the Adjuvant Treatment of Postmenopausal Women with Aromatase Inhibitor Induced Arthralgias Study Chairs: Charles L. Loprinzi, M.D. (Research Base)* Mayo Clinic Study Co-chair: Statistician: Drug Availability Supplied Agent: Testosterone IND #114707 (Alliance) *Investigator having NCI responsibility for this protocol √ Study contributor(s) not responsible for patient care. ClinicalTrials.gov Identifier: NCT01573442 Participating NCTN Organizations Alliance/ Alliance for Clinical Trials in Oncology (lead) ECOG-ACRIN/ ECOG-ACRIN Cancer Research Group NRG/ NRG Oncology SWOG/ SWOG 1 NCI Version Date: 10/09/2018 Update #6 Alliance A221102 Cancer Trials Support Unit (CTSU) Contact Information For regulatory requirements: For patient enrollments: For Study data submission Regulatory documentation must Please refer to the patient Legacy NCCTG sites will submit be submitted to the CTSU via enrollment section of the electronic CRFs via: the Regulatory Submission protocol for instructions on using NCCTG Remote Data Entry Portal. the Oncology Patient Enrollment System. Regulatory Submission Portal: Network (OPEN) which can be (Sign in at www.ctsu.org, and accessed at Sites not previously affiliated select the Regulatory https://www.ctsu.org/OPEN_SY with NCCTG will submit paper Submission sub-tab under the STEM/ or CRFs to: Regulatory tab.) https://OPEN.ctsu.org. Alliance Statistics and Data Center Institutions with patients waiting Contact the CTSU Help Desk Attention: that are unable to use the Portal with any OPEN-related should alert the CTSU questions at Regulatory Office immediately at to receive further instruction and support. Do not submit study data or forms to CTSU Data Operations. Contact the CTSU Regulatory Do not copy the CTSU on data Help Desk at submissions. for regulatory assistance The most current version of the study protocol and all supporting documents must be downloaded from the protocol-specific Web page of the CTSU Member Web site located at https://www.ctsu.org. Access to the CTSU members’ website is managed through the Cancer Therapy and Evaluation Program - Identity and Access Management (CTEP-IAM) registration system and requires user log on with CTEP-IAM username and password. Permission to view and download this protocol and its supporting documents is restricted and is based on person and site roster assignment housed in the CTSU RSS. For clinical questions (i.e. patient eligibility or treatment-related) Contact the Research Base Quality Assurance Specialist (listed in Protocol Resources table on next page). For non-clinical questions (i.e. unrelated to patient eligibility, treatment, or clinical data submission) contact the CTSU Help Desk by phone or e-mail: CTSU General Information Line – , or . All calls and correspondence will be triaged to the appropriate CTSU representative. The CTSU Website is located at https://www.ctsu.org. 2 NCI Version Date: 10/09/2018 Update #6 Alliance A221102 Protocol Resources Expedited Adverse Event Reporting https://eapps-ctep.nci.nih.gov/ctepaers/ OPEN (Oncology Patient Enrollment Network) https://open.ctsu.org Biospecimen Management System http://bioms.allianceforclinicaltrialsinoncology.org Questions: Contact Name: Patient eligibility*, test schedule, treatment delays/interruptions/adjustments, dose modifications, adverse events, forms completion and submission Drug administration, infusion pumps, nursing guidelines Forms completion and submission Protocol document, consent form, Regulatory issues Adverse Events (CTEP-AERS, MedWatch, Non- AER, AML/MDS) Non-paraffin biospecimens *No waivers of eligibility per NCI 3 NCI Version Date: 10/09/2018 Update #6 Alliance A221102 Schema Prior to Update #3, patients were treated with a pellet form of testosterone, which was inserted via surgical implant. Effective with the issuance and local IRB approval of Update #3 to this protocol, new patients are to be randomized to the topical form of testosterone. Those patients randomized to the pellet form will complete the study according to the original protocol and will receive their second pellet as planned. Randomization Baseline Week Subcutaneous Testosterone Subcutaneous placebo Q 3 months x 6 months. Q 3 months x 6 months. First insertion after 1 week baseline and then First insertion after 1 week baseline and then repeat at 3 months (see section 7.1a). repeat at 3 months (see section 7.1a). Topical Testosterone Topical Placebo Once daily for 6 months, applied to skin as Once daily for 6 months, applied to skin as directed (see section 7.1b). directed (see section 7.1b). Observation for Subcutaneous: Monthly up to 6 months. Not needed for patients who complete 6 months of study treatment (see section 13.0). Observation for Topical: Monthly up to 6 months. Not needed for patients who complete 6 months of study treatment (see section 13.0). Off Study Baseline cycle length = 7 days Cycle 1 length = 90 days Cycle 2 length = 90 days NOTE: Cycle is an Alliance data management tool to facilitate consistent remote data entry. Generic name: Testosterone Generic name: Placebo Brand name(s): Brand name(s): Abbreviation: TESTO Abbreviation: PLACEB Availability: Research Base Pharmacy Availability: Research Base Pharmacy 4 NCI Version Date: 10/09/2018 Update #6 Alliance A221102 Table of Contents Section Page 1.0 Background .................................................................................................................................... 7 1.1 Executive Summary .................................................................................................................. 7 1.2 Review of Related Research ...................................................................................................... 7 1.3 Aromatase Inhibitors and Arthralgia ......................................................................................... 7 1.4 Summary of ART Therapy Data ............................................................................................... 8 1.5 The Androgen Receptor, Androgens and Breast Cancer ......................................................... 11 1.6 Androgen Receptor Expression in Breast Tissue .................................................................... 12 1.7 Circulating Androgens in Women ........................................................................................... 12 1.8 Androgens and Breast Cancer ................................................................................................. 13 1.9 Androgen Replacement Safety ................................................................................................ 13 1.10 Effect of AI and T combination (ART) ................................................................................... 14 1.11 CCOP Feasibility ..................................................................................................................... 14 1.12 Study Duration ........................................................................................................................ 14 1.13 Testosterone preparation to use for Pellet Insertion ................................................................ 15 1.14 Summary ................................................................................................................................. 16 1.15 Reasoning for Topical Application ......................................................................................... 17 2.0 Goals .............................................................................................................................................. 17 2.1 Primary .................................................................................................................................... 17 2.2 Secondary ................................................................................................................................ 17 2.3 Ancillary .................................................................................................................................. 17 3.0 Patient Eligibility ......................................................................................................................... 17 3.1 Inclusion Criteria ..................................................................................................................... 17 3.2 Exclusion Criteria .................................................................................................................... 18 4.0 Test Schedule ................................................................................................................................ 19 5.0 Stratification Factors ................................................................................................................... 20 6.0 Registration/Randomization Procedures ................................................................................... 20 6.1 CTEP / DCP Registration Procedures ..................................................................................... 20 6.2 Site Registration Requirements – IRB Approval .................................................................... 21 6.3 Patient Randomization ............................................................................................................ 22 6.4 Procedures for Double-Blinding the Treatment Assignment .................................................. 24 7.0 Protocol Treatment .....................................................................................................................
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