Doxorubicin With Upfront Dexrazoxane Plus Olaratumab for the Treatment of Advanced or Metastatic Soft Tissue Sarcoma

Inclusion Criteria:

- Histologically confirmed grade 2 or 3 soft tissue sarcoma that is unresectable or
metastatic. Surgery for primary or metastatic disease after chemotherapy following a
response is allowed. Patients with the following tumor types are eligible:

- Undifferentiated pleomorphic sarcoma

- Leiomyosarcoma

- Malignant fibrous histiocytoma

- Liposarcoma (myxoid/round cell, pleomorphic or dedifferentiated)

- Synovial sarcoma

- Myxofibrosarcoma

- Angiosarcoma

- Fibrosarcoma

- Malignant peripheral nerve sheath tumor

- Epithelioid sarcoma

- Unclassified high-grade sarcoma (not otherwise specified)

- Soft tissue sarcoma for which treatment with an anthracycline is appropriate at
the approval of the Principal Investigator (PI)

- Measurable disease according to RECIST 1.1; that is, measurable disease defined as
lesions that can be accurately measured in at least one dimension (longest diameter to
be recorded) as ≥ 10 mm with CT scan, as ≥ 20 mm by chest x-ray, or ≥ 10 mm with
calipers by clinical exam.

- Planning to initiate treatment with doxorubicin (starting dose 75 mg/m2) and
olaratumab (starting dose of 15 mg/kg) as routine care.

- Prior adjuvant chemotherapy with gemcitabine and/or docetaxel/paclitaxel is allowed.

- At least 18 years of age.

- ECOG performance status of 0 or 1

- Adequate organ function defined as:

- Leukocytes ≥ 3,000/mcL

- Absolute neutrophil count ≥ 1,500/mcl

- Platelets ≥ 100,000/mcl

- Total bilirubin ≤ 1.5 x IULN

- AST(SGOT)/ALT(SGPT) ≤ 3.0 x IULN

- Creatinine ≤ IULN OR Creatinine clearance ≥ 60 mL/min/1.73 m^2 for patients with
creatinine levels above institutional normal. Creatinine clearance should be
calculated using the actual weight from day 1 of cycle

- Women of childbearing potential and men must agree to use adequate contraception
(hormonal or barrier method of birth control, abstinence) prior to study entry and for
the duration of study participation. Should a woman become pregnant or suspect she is
pregnant while participating in this study, she must inform her treating physician
immediately.

- Able to understand and willing to sign an IRB approved written informed consent
document (or that of legally authorized representative, if applicable).

Exclusion Criteria:

- Myocardial infarction within the past 12 months, or stable or unstable angina.

- Systolic heart failure defined as left ventricular ejection fraction ≤ 45%.

- Symptomatic valvular heart disease.

- Prior chemotherapy for advanced or metastatic disease.

- Known brain metastases.

- Prior or second primary malignancies within the last two years (except carcinoma in
situ of the cervix, non-metastatic prostate cancer, or basal cell or squamous cell
carcinoma of the skin which were treated with local resection only; prior adjuvant
androgen deprivation therapy in the case of prostate cancer is permitted, but current
adjuvant androgen deprivation therapy is not).

- Currently receiving any investigational agents.

- A history of allergic reactions attributed to compounds of similar chemical or
biologic composition to dexrazoxane or other agents used in the study.

- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, or psychiatric illness/social
situations that would limit compliance with study requirements.

- Pregnant and/or breastfeeding. Patient must have a negative pregnancy test within 14
days of study entry.

- Known HIV-positivity on combination antiretroviral therapy because of the potential
for pharmacokinetic interactions with dexrazoxane. In addition, these patients are at
increased risk of lethal infections when treated with marrow-suppressive therapy.
Appropriate studies will be undertaken in patients receiving combination
antiretroviral therapy when indicated.

- Prior treatment with anthracyclines.