Vitamin B12 for Aromatase Inhibitors Associated Musculoskeletal Symptoms in Breast Cancer

NCT04205786 | Withdrawn

• 1 other identifier: CASE5119
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

Treatment of hormone receptor (HR)-positive breast cancer with Aromatase Inhibitors (AIs) can lead to associated musculoskeletal pain and may cause patients to discontinue important treatment. This is a randomized controlled trial assessing the affect of Vitamin B12 on AI-associated joint pain and other outcomes. Participants will be randomly assigned 1:1 to treatment or control arm. The primary objective of this study is:

• To assess whether daily oral Vitamin B12 decreases average joint pain in women with AI-Associated Musculoskeletal Symptoms Secondary objectives include:
• To investigate whether daily vitamin B12 improves functional quality of life
• To explore the impact of treatment on serum inflammatory cytokine levels (C- reactive protein) between baseline and various points in treatment.

Conditions

HR-positive Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Change in average joint pain according to the Brief Pain Inventory - Short Form (BPI- SF)

  Change in average joint pain according to the Brief Pain Inventory - Short Form (BPI- SF) average pain score. This item has a scale of 0 to 10 with 0 indicating "No pain" and 10 indicating "Pain as bad as you can imagine"

  At baseline, day 45 (+/- 10 days), and at day 90 (+/- 10 days)

Secondary Outcomes (2)

• Change in worst joint pain according to the BPI-SF

  At day 90 (+/- 10 days)

• Quality of life (QOL) as measured by Functional Assessment of Cancer Therapy-Endocrine Scale (FACT-ES)

  At baseline, day 45 (+/- 10 days), and at day 90 (+/- 10 days)

Other Outcomes (1)

• Serum inflammatory cytokine levels (C- reactive protein)

  At baseline, day 45 (+/- 10 days), and at day 90 (+/- 10 days)

Study Arms (2)

Control - Standard of Care

ACTIVE COMPARATOR

Day 0: * Baseline questionnaires: FACT-ES, BPI-SF, Assessment of AI Adherence, Demographics, CRF, and Supplemental Agents Reporting Form * Blood collection * Continue Usual Care Day 45: * Repeat of baseline questionnaires with addition of vitamin B12 supplements form and investigational agent accountability record * Blood collection * Continue Usual Care Day 90: -Repeat of day 45

Other: Blood collection; Other: Brief Pain Inventory - Short Form survey; Other: FACT-ES Trial Outcome Index (Version 4); Other: Questionnaire to Assess Adherence to Aromatase Inhibitors; Other: Demographics Questionnaire

Study Medication Group (B12)

EXPERIMENTAL

Day 0: * Baseline questionnaires: FACT-ES, BPI-SF, Assessment of AI Adherence, Demographics, CRF, and Supplemental Agents Reporting Form * Blood collection * Oral intake of Vitamin B12 Daily in the morning Day 45 * Repeat of baseline questionnaires with addition of investigational agent accountability record * Blood collection * Oral intake of Vitamin B12 Daily in the morning Day 90: -Repeat of day 45 without additional study drug intake.

Dietary Supplement: Vitamin B12; Other: Blood collection; Other: Brief Pain Inventory - Short Form survey; Other: FACT-ES Trial Outcome Index (Version 4); Other: Questionnaire to Assess Adherence to Aromatase Inhibitors; Other: Demographics Questionnaire

Interventions

Vitamin B12 DIETARY_SUPPLEMENT

Vitamin B12, orally, 2500 mcg, daily, for 90 days

Study Medication Group (B12)

Blood collection OTHER

Blood collection for laboratory testing will occur within 10 days of signing the consent form, on day 45 +/- 10 days, and on day 90 +/- 10 days. It will include: 1. Serum B12 levels 2. CRP 3. Homocysteine level 4. MMA

Control - Standard of Care; Study Medication Group (B12)

Brief Pain Inventory - Short Form survey OTHER

Brief Pain Inventory - Short Form survey

Control - Standard of Care; Study Medication Group (B12)

FACT-ES Trial Outcome Index (Version 4) OTHER

FACT-ES Trial Outcome Index (Version 4)

Control - Standard of Care; Study Medication Group (B12)

Questionnaire to Assess Adherence to Aromatase Inhibitors OTHER

Questionnaire to Assess Adherence to Aromatase Inhibitors

Control - Standard of Care; Study Medication Group (B12)

Demographics Questionnaire OTHER

Demographics Questionnaire

Control - Standard of Care; Study Medication Group (B12)

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects must have histologically or cytologically confirmed estrogen receptor (ER) and/or progesterone receptor (PgR) positive invasive carcinoma of the breast (Stage I-III) with no evidence of metastatic disease (M0).
• Subjects must have completed mastectomy or breast sparing surgery, and must have recovered from all side effects of the surgery. Patients should have recovered from all Grade 2 or higher side effects of chemotherapy and/or radiation therapy with the exception of alopecia and peripheral neuropathy. Concurrent bisphosphonate and trastuzumab therapies are allowed
• Patients must have aromatase inhibitor (AI) associated musculoskeletal symptoms that began or increased after starting AI therapy. New musculoskeletal pain must not be due specifically to fracture or traumatic injury
• Subjects must currently be taking one of the following aromatase inhibitor (AI) doses for at least 14 days prior to registration and plan to continue for at least an additional 180 days after registration:
• Anastrozole (Arimidex) 1 mg daily OR
• Letrozole (Femara) 2.5 mg daily OR
• Exemestane (Aromasin) 25 mg daily
• Patients must be post-menopausal, as defined by at least one of the following:
• ≥ 12 months since their last menstrual period OR
• Prior bilateral oophorectomy OR
• Previous hysterectomy with one or both ovaries left in place (or previous hysterectomy in which documentation of bilateral oophorectomy is unavailable) AND (unless ≥ 60 years of age) FSH values consistent with the institutional normal values for the post-menopausal state.
• Performance status: Patients must have ECOG performance status of 0-2 as assessed by MD or RN
• Patients must have no known allergy or hypersensitivity to vitamin B12
• Must have completed the Brief Pain Inventory Short Form (BPI-SF) within 7 days of enrollment (after signing consent, but prior to starting treatment) and have an "average pain" score of at least 24.
• Patients must not have any contraindicated concurrent illnesses including:

You may not qualify if:

• Subjects receiving any other investigational agents.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to vitamin B12 or other agents used in this study.
• Subjects with uncontrolled intercurrent illness including, but not limited to chronic liver disease, end stage renal disease, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements

Sponsors & Collaborators

• Case Comprehensive Cancer Center: lead

Study Sites (1)

Cleveland Clinic Taussig Cancer Center, Case Comprehensive Cancer Center

Cleveland, Ohio, 44195, United States

Location

MeSH Terms

Interventions

Vitamin B 12; Blood Specimen Collection

Intervention Hierarchy (Ancestors)

Corrinoids; Tetrapyrroles; Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Macrocyclic Compounds; Polycyclic Compounds; Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Zeina Nahleh, MD

  Cleveland Clinic Taussig Cancer Center, Case Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: The study is a randomized controlled trial. Participants will be randomly assigned 1:1 to treatment or control arm.

Study Record Dates

• First Submitted: December 18, 2019
• First Posted: December 19, 2019
• Study Start: August 12, 2021
• Primary Completion: December 1, 2024
• Study Completion: December 1, 2025
• Last Updated: August 21, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will share

Locations

US (1)