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

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.