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Doxorubicin Hydrochloride and Dexrazoxane Hydrochloride in Treating Patients with Advanced or Metastatic Soft Tissue Sarcoma That Cannot Be Removed by Surgery

Trial Status: Closed to Accrual

This phase II trial studies how well doxorubicin hydrochloride and dexrazoxane hydrochloride work in treating patients with soft tissue sarcoma that has spread to other places in the body and usually cannot be cured or controlled with treatment and cannot be removed by surgery. Drugs used in chemotherapy, such as doxorubicin hydrochloride work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Chemoprotective drugs, such as dexrazoxane hydrochloride, may protect normal cells from the side effects of chemotherapy. Giving doxorubicin hydrochloride and dexrazoxane hydrochloride may work better in treating patients with 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 Response Evaluation Criteria in Solid Tumors (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 computed tomography (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 of 75 mg/m^2) as routine care
  • Prior adjuvant chemotherapy with gemcitabine and/or docetaxel/paclitaxel is allowed
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  • Leukocytes >= 3,000/mcL
  • Absolute neutrophil count >= 1,500/mcl
  • Platelets >= 100,000/mcl
  • Total bilirubin =< 1.5 x institutional upper limit of normal (IULN)
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [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 the 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 Institutional Review Board (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 human immunodeficiency virus (HIV)-positivity on combination antiretroviral therapy; 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

Missouri

Saint Louis
Siteman Cancer Center at Washington University
Status: CLOSED_TO_ACCRUAL
Contact: Brian Andrew Van Tine
Phone: 314-747-8475

PRIMARY OBJECTIVE:

I. To determine progression-free survival (PFS) in patients with metastatic soft tissue sarcoma who are treated with doxorubicin (doxorubicin hydrochloride) in combination with dexrazoxane (dexrazoxane hydrochloride).

SECONDARY OBJECTIVES:

I. To determine cardiac-related mortality in patients with metastatic soft tissue sarcoma who are treated with doxorubicin in combination with dexrazoxane.

II. To determine incidence of heart failure or cardiomyopathy in patients with metastatic soft tissue sarcoma who are treated with doxorubicin in combination with dexrazoxane.

III. To evaluate additional echocardiogram parameters of left ventricular ejection fraction to determine if either 3-dimensional (3D) echocardiogram or ventricular strain is able to serve as an early marker of cardiac dysfunction compared to 2-dimensional (2D) echocardiogram modified Simpson’s biplane method of left ventricular ejection fraction (LVEF).

OUTLINE: Patients are assigned to 1 of 2 cohorts.

COHORT 1: Patients receive dexrazoxane hydrochloride intravenously (IV) over 15 minutes and doxorubicin hydrochloride IV on day 1.

COHORT 2: Patients receive doxorubicin hydrochloride IV on day 1.

In both cohorts, courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients in cohort 1 are followed up every 3 months for up to 5 years.

Trial Phase Phase II

Trial Type Treatment

Lead Organization
Siteman Cancer Center at Washington University

Principal Investigator
Brian Andrew Van Tine

  • Primary ID 201510049
  • Secondary IDs NCI-2015-01777
  • Clinicaltrials.gov ID NCT02584309