Clinical trial NCT06518837: Tirzepatide for Weight Loss Intervention in Early-Stage Hormone Receptor Positive/HER2 Negative Breast Cancer
Official title: FITWISE: Feasibility Study of Tirzepatide for Weight Loss Intervention in Early-Stage Hormone Receptor Positive/HER2 Negative Breast Cancer
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Hormone Receptor-Positive Breast Cancer
HER2-Negative Breast Cancer
Keywords: Weight Loss
Body Weight Reduction
Feasibility of Weight Loss Intervention
invasive Disease-Free Survival (IDFS)
Body Mass Index (BMI)
Body Fat Distribution
Metabolic Markers
Circulating Tumor DNA (ctDNA)
Tirzepatide
GIP and GLP-1 dual agonist
Black patients
distant relapse-free survival (DRFS)
Lead sponsor: Rutgers, The State University of New Jersey
Sponsor class: OTHER
Collaborators: name: Ludwig Institute for Cancer Research
First posted: 2024-07-24
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Tirzepatide will be administered subcutaneously in the stomach, upper arm, or thigh. Administer once weekly at any time of day, with or without meals. Start with an initial dosage of 2.5 mg. After 4 weeks, increase to 5 mg weekly. Further increases may be made in 2.5 mg increments after at least 4 weeks on the current dose, aiming for a target of 15 mg (i.e., 2.5 mg, 5 mg, 7.5 mg, 10 mg, 12.5 mg, or 15 mg). Consider treatment tolerability when selecting the maintenance dose. If not tolerated, consider the next lower maintenance dose. Recommended maintenance doses are 5 mg, 10 mg, or 15 mg, with 5 mg as the lowest evaluable dose. The 2.5 mg dose is not a maintenance dose. The maximum allowed dosage is 15 mg once weekly.

20 Black and 20 Non-Black breast cancer patients will be enrolled. More black patients will be enrolled to enrich this cohort with the population that has an established significant disparity in HR+ breast cancer and obesity related outcomes.
Primary purpose: TREATMENT

Brief summary: This clinical trial aims to evaluate the effectiveness of tirzepatide in achieving a 5% or more body weight reduction in patients undergoing adjuvant treatment for hormone receptor-positive, HER2-negative (HR+/Her2-) breast cancer. The study will also assess the safety and tolerability of tirzepatide, its feasibility based on discontinuation rates, and completion of treatment. Secondary objectives include evaluating 3-year invasive disease-free survival (IDFS) and distant relapse-free survival (DRFS), changes in BMI and body fat distribution, metabolic markers, and circulating tumor DNA (ctDNA).

Detailed description: The primary objective of this clinical trial is to determine the proportion of patients who achieve a 5% or greater reduction in body weight by the end of the study treatment with tirzepatide, during adjuvant treatment for hormone receptor-positive, HER2-negative (HR+/Her2-) breast cancer. Secondary objectives include assessing the safety and tolerability of tirzepatide for weight loss during this treatment. The feasibility of using tirzepatide for weight loss intervention will be evaluated through discontinuation rates and completion of the treatment course. Additionally, the trial will determine the 3-year invasive disease-free survival (IDFS) and 3-year distant relapse-free survival (DRFS) with the use of tirzepatide. The study will also assess changes in Body Mass Index (BMI), body fat distribution (measured via Waist/Hip Ratio (WHR) and waist circumference), and obesity-related metabolic markers (including Blood Pressure, fasting insulin, fasting blood glucose, HgbA1c, cholesterol, LDL, HDL, triglycerides, IGF1, estrogen, and testosterone). Finally, the trial will monitor for circulating tumor DNA (ctDNA) and assess changes when using tirzepatide for weight loss in the adjuvant treatment of HR+/Her2- breast cancer. Quality of Life assessments will be obtained and exploratory objectives investigating adipokines (adiponectin, leptin) and their receptors, metabolomic pathways and immune cell metabolism will be conducted.

Eligibility criteria: Inclusion Criteria:

* Consent: Be willing and able to provide written informed consent for the trial.
* Age: Male or Female patients aged 18 years or older.
* Breast Cancer Diagnosis: Have hormone receptor-positive (HR+), HER2-negative (HER2-) breast cancer previously diagnosed by biopsy. HR status is defined as estrogen receptor (ER) \>10% and/or progesterone receptor (PR) \>10%; HER2 status is defined as immunohistochemistry (IHC) 0 or 1+ or IHC 2+, fluorescence in situ hybridization (FISH) negative.
* Stage: Have previously untreated early-stage, clinical or anatomic stage I, II, or III hormone receptor-positive breast cancer.
* Definitive Treatment: Have had definitive treatment with curative intent for breast cancer, including surgery, chemotherapy, and radiotherapy as indicated.
* Body Mass Index (BMI): Have a BMI of 30 kg/m² or more, or a BMI of 27 kg/m² or more with one weight-related complication (e.g., hypertension, type 2 diabetes, dyslipidemia, obstructive sleep apnea, or cardiovascular disease).
* Performance Status: Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
* Cardiac Function: Have a left ventricular ejection fraction (LVEF) of 50% or greater, or greater than the institution's lower limit of normal (LLN), as assessed by echocardiogram (ECHO) or multigated acquisition (MUGA) scan performed at screening.
* Organ Function: Demonstrate adequate organ function in screening labs.
* Tumor Specimens: Have archived biopsy or surgical tumor specimens available as tumor blocks or unstained slides.

Exclusion Criteria:

* Other Clinical Studies: Is currently enrolled, or will enroll in, a different clinical study in which investigational therapeutic procedures are performed or investigational therapies are administered while participating in this study.
* Stage IV Breast Cancer: Have stage IV, metastatic breast cancer.
* Cancer Type: Have HER2-positive or triple-negative breast cancer.
* Active Malignancy: Have a concomitant active malignancy.
* Performance Status: Have an Eastern Cooperative Oncology Group (ECOG) performance status greater than 2.
* Body Mass Index: Have a BMI of less than 27 kg/m².
* Type 1 Diabetes Mellitus: Have type 1 diabetes mellitus.
* Gastric Emptying Abnormality: Have a known clinically important gastric emptying abnormality (e.g., severe gastroparesis or gastric outlet obstruction) or chronically took drugs that directly affect gastrointestinal motility.

Primary outcomes:
measure: Weight Loss Reduction with Tirzepatide during Adjuvant Treatment for HR+/Her2- Breast Cancer (Measured by Body Weight Reduction)
timeFrame: Through study completion, total of two years.
Secondary outcomes:
measure: Safety and Tolerability of Tirzepatide for Weight Loss during Adjuvant Treatment for HR+/Her2- Breast Cancer (Measured by Incidence of Adverse Events Using CTCAE v5.0)
timeFrame: Adverse events will be monitored through study completion for two years.
measure: Feasibility of Tirzepatide for Weight Loss Intervention during Adjuvant Treatment for HR+/Her2- Breast Cancer (Assessed by Discontinuation Rates and Completion of Treatment Course).
timeFrame: Feasibility will be evaluated through study completion for two years.
measure: Clinical Efficacy of Tirzepatide during Adjuvant Treatment for HR+/Her2- Breast Cancer (Measured by 3-Year Invasive Disease-Free Survival and 3-Year Distant Relapse-Free Survival)
timeFrame: Patients will be monitored for recurrence through study completion and an additional year, for total three years.
measure: Assessment of Obesity Measurements Using Tirzepatide for Weight Loss during Adjuvant Treatment for HR+/Her2- Breast Cancer, as measured by Waist/Hip Ratio (WHR), and waist circumference.
timeFrame: Obesity measurements will be evaluated through study completion for two years.
measure: Assessment of Obesity Measurements Using Tirzepatide for Weight Loss during Adjuvant Treatment for HR+/Her2- Breast Cancer, Weight and height will be combined to report BMI in kg/m^2.
timeFrame: Obesity measurements will be evaluated through study completion for two years.
measure: Assessment of Obesity-Related Metabolic Markers Using Tirzepatide for Weight Loss during Adjuvant Treatment for HR+/Her2- Breast Cancer Assessment of Blood Pressure Changes unit of Measure: Millimeters of mercury (mm Hg).
timeFrame: Metabolic markers will be evaluated through study completion for two years.
measure: Assessment of Obesity-Related Metabolic Markers Using Tirzepatide for Weight Loss during Adjuvant Treatment for HR+/Her2- Breast Cancer Assessment of fasting insulin changes, unit of Measure: Milli-international units per liter (mIU/L)
timeFrame: Metabolic markers will be evaluated through study completion for two years.
measure: Assessment of Obesity-Related Metabolic Markers Using Tirzepatide for Weight Loss during Adjuvant Treatment for HR+/Her2- Breast Cancer, Assessment of Fasting Blood Glucose Changes, Unit of Measure: Millimoles per liter (mmol/L)
timeFrame: Metabolic markers will be evaluated through study completion for two years.
measure: Assessment of Obesity-Related Metabolic Markers Using Tirzepatide for Weight Loss during Adjuvant Treatment for HR+/Her2- Breast Cancer Assessment of HgbA1c Changes, Unit of Measure: Millimoles per mole (mmol/mol)
timeFrame: Metabolic markers will be evaluated through study completion for two years.
measure: Assessment of Obesity-Related Metabolic Markers Using Tirzepatide for Weight Loss during Adjuvant Treatment for HR+/Her2- Breast Cancer Assessment of Cholesterol (Total, LDL, HDL) Changes Unit of Measure: Milligrams per deciliter (mg/dl)
timeFrame: Metabolic markers will be evaluated through study completion for two years.
measure: Assessment of Obesity-Related Metabolic Markers Using Tirzepatide for Weight Loss during Adjuvant Treatment for HR+/Her2- Breast Cancer, Assessment of Triglyceride Changes Unit of Measure: Millimoles per liter (mmol/L)
timeFrame: Metabolic markers will be evaluated through study completion for two years.
measure: Assessment of Obesity-Related Metabolic Markers Using Tirzepatide for Weight Loss during Adjuvant Treatment for HR+/Her2- Breast Cancer, Assessment of IGF1 Changes, Unit of Measure: Nanograms per milliliter (ng/ml)
timeFrame: Metabolic markers will be evaluated through study completion for two years.
measure: Assessment of Obesity-Related Metabolic Markers Using Tirzepatide for Weight Loss during Adjuvant Treatment for HR+/Her2- Breast Cancer, Assessment of Estrogen Changes, Unit of Measure: Picograms per milliliter (pg/ml)
timeFrame: Metabolic markers will be evaluated through study completion for two years.
measure: Assessment of Obesity-Related Metabolic Markers Using Tirzepatide for Weight Loss during Adjuvant Treatment for HR+/Her2- Breast Cancer Assessment of Testosterone Changes, Unit of Measure: Nanograms per deciliter (ng/dL)
timeFrame: Metabolic markers will be evaluated through study completion for two years.
measure: Monitoring Circulating Tumor DNA (ctDNA) Levels Using Tirzepatide for Weight Loss during Adjuvant Treatment for HR+/Her2- Breast Cancer (Detection and Changes in ctDNA Levels during Treatment).
timeFrame: ctDNA levels will be monitored through study completion for two years.
Other outcomes:
Locations:
city: Elizabeth
country: United States
facility: Trinitas Comprehensive Cancer Center
state: New Jersey
city: Hamilton
country: United States
facility: RWJ Barnabas Health - Robert Wood Johnson University Hospital, Hamilton
state: New Jersey
city: Livingston
country: United States
facility: RWJBarnabas Health - Cooperman Barnabas, Livingston
state: New Jersey
city: Long Branch
country: United States
facility: RWJBarnabas Health - Monmouth Medical Center
state: New Jersey
city: New Brunswick
country: United States
facility: Rutgers Cancer Institute
state: New Jersey
city: Newark
country: United States
facility: RWJBarnabas Health - Newark Beth Israel Medical Center
state: New Jersey
city: Somerville
country: United States
facility: RWJ Barnabas Health - Robert Wood Johnson University Hospital, Somerset
state: New Jersey
Study officials:
affiliation: Rutgers Cancer Institute
name: Coral Omene, MD., PhD
role: PRINCIPAL_INVESTIGATOR
References: