Pioglitazone Therapy Targeting Fatigue in Breast Cancer

NCT ID: NCT05013255

Last Updated: 2025-04-08

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-12-23
• Study Completion Date: 2026-12-31

Brief Summary

The goal of this project is to evaluate the therapeutic potential of pioglitazone (PIO) to target underlying mechanisms that promote muscle fatigue in patients with breast cancer. This represents an off-label use of this compound, both in terms of the patient population and the clinical phenotype targeted. The central research hypothesis of this study is that daily pioglitazone will restore transcriptional downregulation of pathways within skeletal that promote fatigue.

Detailed Description

Fatigue is commonly reported in cancer patients, but is not treated due to the absence of viable therapies. At the time of diagnosis, prior to treatment, nearly all breast cancer patients have some degree of muscle dysfunction resulting in fatigue that ranges from mild to debilitating and may worsen with chemotherapy, radiation, and/or surgery. A significant gap in knowledge exists with respect to targetable mechanisms to alleviate fatigue in patients with cancer. The goal of this project is to evaluate the therapeutic potential of pioglitazone (PIO) to target underlying mechanisms that promote muscle fatigue in patients with breast cancer. This represents an off-label use of this compound, both in terms of the patient population and the clinical phenotype targeted. The central research hypothesis of this study is that daily pioglitazone will restore transcriptional downregulation of pathways within skeletal that promote fatigue. The investigators believe this trial will provide the clinical data on optimal PIO dose to affect muscle gene expression in patients with breast cancer. This data will be used to support a larger clinical trial in patients with and without breast cancer to determine PIO therapy effects on muscle fatigue.

Pioglitazone is an FDA-approved drug that is used to treat insulin resistance in patients with diabetes by targeting PPARγ activity, although this drug also affects mitochondrial function through PPARγ regulation. Therefore, the investigators will test the central research hypothesis that daily pioglitazone will restore transcriptional downregulation of pathways within skeletal that promote fatigue. Specific Aim 1 will determine the molecular signature within skeletal muscle in response to low dose and high dose pioglitazone therapy. It is predicted that daily pioglitazone therapy will reverse the breast cancer-associated downregulation of mitochondrial and metabolic genes in skeletal muscle. Specific Aim 2 will determine the effects of low dose and high dose pioglitazone therapy on perceptions of fatigue. It is predicted that daily pioglitazone therapy will improve patient reported perceptions of fatigue.

This is a Phase 2B Trial to determine the lowest effective dose of pioglitazone for affecting skeletal muscle gene expression in breast cancer patients without diabetes (dose-finding study). At the time of registration, subjects will be randomized to either the low dose (15mg PIO; n=10) or the high dose (30mg PIO; n=10) group, or a no-drug control group (n=10). Drug therapy will last for 2 weeks, leading into a scheduled mastectomy. Subjects will be provided with a 2 week supply of PIO on Study Day 1 to be taken orally once per day. Following surgery and muscle biopsy collection subjects will be followed for adverse events, fatigue and body composition for 30 days through their first post-op visit. The total study duration will be 6-weeks (2 weeks of drug treatment + 4 weeks until follow-up visit).

Conditions

Breast Cancer; Muscle Fatigue

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

No Drug

Subjects will be assigned to a no drug control group based on the randomization lists prepared by the WVUCI Biostatistics Core. This is a 1:1:1 randomization (10 in each group) without any planned stratification.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Pioglitazone 15mg Dose

Subjects will be given PIO 15mg once daily, based on the randomization lists prepared by the WVUCI Biostatistics Core. This is a 1:1:1 randomization (10 in each group) without any planned stratification.

Group Type: ACTIVE_COMPARATOR

Pioglitazone 15mg

Intervention Type: DRUG

PIO 15mg orally once daily for 2 weeks

Pioglitazone 30mg Dose

Subjects will be given PIO 30mg once daily, based on the randomization lists prepared by the WVUCI Biostatistics Core. This is a 1:1:1 randomization (10 in each group) without any planned stratification.

Group Type: ACTIVE_COMPARATOR

Pioglitazone 30 mg

Intervention Type: DRUG

PIO 30mg orally once daily for 2 weeks

Interventions

Pioglitazone 15mg

PIO 15mg orally once daily for 2 weeks

Intervention Type: DRUG

Pioglitazone 30 mg

PIO 30mg orally once daily for 2 weeks

Intervention Type: DRUG

Other Intervention Names

Actos; Actos

Eligibility Criteria

Inclusion Criteria

• Subjects must have histologically or cytologically confirmed luminal (ER+/PR+ Her2/neu-) Breast Cancer.
• Subjects must have received no prior therapies besides chemotherapy in the neoadjuvant setting.
• Subject must have a planned surgical (mastectomy) date within 2 weeks of starting treatment.
• 5 Subjects must have normal organ as defined below:

• Hemoglobin within normal institutional limits (or >10?)
• Fasting Blood Glucose within normal institutional limits
• Serum Creatinine within normal institutional limits
• Liver Function (AST and ALT, Alk phosphatase, Total Bilirubin) within normal limits
• Subject does not have a prior diagnosis of diabetes or currently taking any medications to lower blood glucose levels.
• Subjects must have the ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria

• Prior diagnosis of Congestive Heart Failure (CHF), Bladder cancer, osteoporosis, bariatric surgery
• Subjects receiving any other investigational agents or known agents to have a major interaction with PIO to include clopidogrel, gatifloxacin, gemfibrozil, leflunomide, lomitapide, lumateperone, mipomersen, pexideartinib and teriflunomide, insulin, Lyrica, Synthroid.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to Pioglitazone.
• Subjects with uncontrolled intercurrent illness including, but not limited to ongoing or active infection, unstable angina pectoris, cardiac arrhythmia, active alcoholism or psychiatric illness/social situations that would limit compliance with study requirements.
• Pregnant or breastfeeding are excluded from this study because Pioglitazone has the potential for teratogenic or abortifacient effects. Because there is an unknown, but potential risk for adverse events in nursing infants secondary to treatment of the mother with PIO, breastfeeding should be discontinued if the mother is treated with PIO. These potential risks may also apply to other agents used in this study.

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

West Virginia University

OTHER

Sponsor Role: lead

Responsible Party

Jessica Partin

Assistant Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Kristin H Lupinacci, DO

Role: PRINCIPAL_INVESTIGATOR

West Virginia University

Locations

West Virginia University Cancer Institute

Morgantown, West Virginia, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Kristin Lupinacci, DO

Role: CONTACT

kristin.lupinacci@hsc.wvu.edu

3042931022

Emidio Pistilli, PhD

Role: CONTACT

epistilli2@hsc.wvu.edu

304-293-0291

Facility Contacts

Kristin Lupinacci, DO

Role: primary

kristin.lupinacci@hsc.wvu.edu

304-293-1022

Other Identifiers

2103254164

Identifier Type: -

Identifier Source: org_study_id