Doxorubicin With Upfront Dexrazoxane for the Treatment of Advanced or Metastatic Soft Tissue Sarcoma
Condition: Sarcoma, Soft Tissue; Soft Tissue Sarcoma; Undifferentiated Pleomorphic Sarcoma; Leiomyosarcoma; Liposarcoma; Synovial Sarcoma; Myxofibrosarcoma; Angiosarcoma; Fibrosarcoma; Malignant Peripheral Nerve Sheath Tumor; Epithelioid Sarcoma
MeSH terms: Sarcoma; Leiomyosarcoma; Liposarcoma; Sarcoma, Synovial; Hemangiosarcoma; Nerve Sheath Neoplasms; Neurofibrosarcoma; Fibrosarcoma; Histiocytoma, Malignant Fibrous
Intervention: Dexrazoxane; Doxorubicin
Intervention MeSH terms: Doxorubicin; Liposomal doxorubicin; Dexrazoxane; Razoxane
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 73.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The purpose of this research study is to look at whether giving a drug called dexrazoxane
      with standard of care doxorubicin affects the progression of the disease. Dexrazoxane is
      often given at the same time as doxorubicin to help reduce the incidence and severity of
      disease of the heart muscle (which can be caused by doxorubicin).

      In January 2019 Eli Lilly and Company reported that the results of the Phase 3 study of
      olaratumab (Lartruvo), in combination with doxorubicin in patients with advanced or
      metastatic soft tissue sarcoma, did not confirm the clinical benefit of olaratumab in
      combination with doxorubicin as compared to doxorubicin alone. Therefore olaratumab is being
      removed from the front line standard of care regimen. Amendment #9 was made to the protocol
      to reflect these changes to the standard of care treatment.
    

Eligibility criteria:

        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) 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.