PROACT AYA: Preventing Overweight/Obesity-Associated Cardiotoxicity With Tirzepatide In Adolescent And Young Adult Cancer Survivors - A Phase 2 Single-Arm, Single-Center Feasibility Study

This is a prospective, single-arm, open-label feasibility trial conducted at the MD Anderson Sarcoma Center and Cardio-Oncology Clinic. The study will enroll young adults (18-39 years) with soft tissue or bone sarcoma who are overweight (BMI 25-29.9 kg/m² with ≥1 cardiovascular risk factor) or obese (BMI ≥30 kg/m²), have completed Dox-based chemotherapy (≥300 mg/m²) approximately three months prior to enrollment, and have preserved LVEF (≥50%) preenrollment.

Inclusion Criteria: * Age 18-39 years at enrollment * Histologically confirmed soft tissue or bone sarcoma with treatment that included Dox ≥ 300 mg/m². * Completed chemotherapy 3 months prior to enrollment; patient must be in remission at the time of enrollment with no planned systemic therapy, radiation therapy, or surgical oncologic intervention anticipated within the next 12 months. * Overweight (BMI 25-29.9 kg/m² with ≥1 cardiovascular risk factor) or obese (BMI ≥30 kg/m²) at the time of enrollment. * LVEF ≥ 50% at the time of enrollment with no symptoms of heart failure (NYHA class I-II). * ECOG performance status ≤2 (equivalent to Karnofsky ≥60%) at the time of enrollment. * Reproductive considerations: * Women of childbearing potential must agree to use adequate contraception (hormonal, barrier, IUD, or abstinence) beginning at enrollment and continuing for the duration of Tirz therapy. * Men must agree to use adequate contraception during study treatment and for 4 months after completion of Tirz. * Pregnancy testing will follow MD Anderson Policy CLN1114. * Ability to provide informed consent and willingness to comply with all study procedures, assessments, and follow-up requirements. Exclusion Criteria: * Preexisting diabetes mellitus requiring pharmacologic therapy. * Prior or current use of GLP-1 receptor agonists. * Ongoing active malignancy or ongoing systemic therapy for cancer treatment. * Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities \> Grade 1) with the exception of alopecia. * History of pancreatitis, medullary thyroid carcinoma, or MEN2. * Current participation in another interventional trial. * Pregnancy or breastfeeding. * Contraindication to GLP-1/GIP receptor agonists. * Psychiatric illness/social situations that would limit compliance with study requirements.