ATX-101 in Advanced Dedifferentiated Liposarcoma and Leiomyosarcoma
Condition: Leiomyosarcoma; Liposarcoma
MeSH terms: Leiomyosarcoma; Liposarcoma
Intervention: ATX-101
Intervention description: Patients will be given ATX-101 at 60 mg/m2 IV weekly in continuous 21 day cycles.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 4.0
Sex: All
Minimum age: 18 Years
Maximum age: 99 Years
Healthy volunteers: No
Keywords: LMS; LPS; ATX-101

Summary:

      The purpose of this study is to evaluate the effectiveness of a new investigational drug,
      ATX-101, for the treatment of dedifferentiated liposarcoma (LPS) and leiomyosarcoma (LMS).
      ATX-101 is an intravenous (IV) drug which blocks the interaction of a protein called PCNA
      with a number of "stress response" proteins. These interactions are thought to be important
      for cancer cell survival and growth. ATX-101 may disrupt these interactions and therefore
      help treat the cancer. In this study, all patients will receive the same treatment. Most of
      the exams, tests, and procedures are part of the usual approach to medical care for this
      condition. However, some additional tests or procedures may be performed, and other tests may
      be performed more frequently than usual.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically confirmed dedifferentiated liposarcoma (LPS) or leiomyosarcoma

          -  ATX-101 in Sarcoma Phase II

          -  (LMS). Pathology review occurs at the center enrolling the patient on this trial.

          -  Disease must be locally advanced and unresectable or metastatic. Disease which may be
             resected but with an associated level of morbidity deemed unacceptable by the treating
             clinician is considered eligible.

          -  Patients must have measurable disease by RECIST criteria version 1.1. In addition, the
             first 10 patients enrolled on the study must have a site of disease amenable to
             image-guided biopsy at minimal risk or less, and must agree to undergo this biopsy.

          -  Patients must evidence of disease progression, either clinically or radiographically,
             within the 12 weeks prior to study enrollment, as determined by the investigator
             enrolling the patient on the study.

          -  Patients must have been treated with at least one prior systemic regimen for advanced
             sarcoma: LMS: Anthracycline-based chemotherapy, or gemcitabine/docetaxel. LPS: No
             specification as to the prior treatment received. Neoadjuvant or adjuvant systemic
             therapy does not qualify as prior treatment unless completed within 6 months of
             disease relapse.

          -  Patients must be age 18 years or older. Because the safety of ATX-101 in patients less
             than 18 years of age has not been characterized, children are excluded from the
             present study.

          -  Patients must demonstrate an Eastern Cooperative Oncology Group (ECOG) performance
             status of ≤2.

          -  Patients must demonstrate normal organ and marrow function as defined below:

          -  Absolute neutrophil count (ANC) ≥ 1,500/mm3

          -  Platelet count ≥ 100,000/mm3

          -  Creatinine ≤ 1.5 times upper limit of normal OR

          -  Calculated creatinine clearance > 45 mL/min*

          -  Total bilirubin ≤ 1.5 times upper limit of normal**

          -  Aspartate transaminase (AST)/aminotransferase (ALT) ≤ 1.5 times upper limit of
             normal**

          -  Notes: Upper limit of normal is defined by the clinical laboratory performing the
             test.

          -  Using the lean body mass formula only (Modified Cockcroft Gault) ** If transaminase
             elevation and/or bilirubin elevation is attributed to the presence of liver
             metastases, a total bilirubin ≤ 2.5 times the upper limit of normal and an AST and ALT
             ≤ 2.5 times the upper limit of normal are permissible. Patients with an elevated
             bilirubin level that is attributed to an inherited disorder, such as Gilbert's
             disease, may be enrolled at the discretion of the principal investigator.

          -  The effects of ATX-101 on the developing human fetus are unknown. For this reason,
             women of child-bearing potential and all men must agree to use adequate contraception
             (for women: hormonal or barrier method of birth control, abstinence; for men: male
             condom, prior vasectomy, or abstinence) prior to study entry and for the duration of
             study participation. Should a woman become pregnant or suspect she is pregnant while
             she or her partner is participating in this study, she should inform her treating
             physician immediately. Men treated or enrolled on this protocol must also agree to use
             adequate contraception prior to the study, for the duration of study participation,
             and 4 months after completion of ATX-101 administration. If patients do not agree to
             the above, they are not considered eligible.

          -  Ability to understand and willingness to sign a written informed consent document.

        Exclusion Criteria

          -  Patients must not have received treatment with any chemotherapy, immunotherapy,
             radiotherapy or an investigational agent for malignancy within the 21 days of
             initiating treatment on this protocol.

          -  Patients may not have received treatment with a small molecule targeted agent
             (including off-label or investigational use) within 14 days of initiating treatment on
             this protocol, provided this represents at least 7 half-lives for that agent.

          -  Toxic effects from any prior therapy (except alopecia) must have resolved to grade 1
             or less according to NCI CTCAE v4.0 or to the patient's baseline by the time of
             initiating treatment on this protocol.

          -  Patients may not have uncontrolled intercurrent illness including, but not limited to,
             ongoing or active infection, symptomatic congestive heart failure, unstable angina
             pectoris, uncontrolled cardiac arrhythmia, cerebrovascular accident within the last
             six months, uncontrolled diabetes mellitus, uncontrolled psychiatric illness or any
             other disease condition that would limit compliance with study requirements in the
             opinion of the principal investigator.

          -  Patients may not be pregnant or nursing. Pregnant women are excluded from this study
             because the teratogenic effects of ATX-101 have not been adequately studied. A
             negative pregnancy test must be documented 7 days or less prior to initiating
             treatment on this protocol. Because there is an unknown but potential risk for adverse
             events to nursing infants secondary to treatment of the mother with ATX-101,
             breastfeeding must be discontinued prior to enrollment.

          -  Patients may not have known active hepatitis B or C infection. In patients with a
             history of hepatitis B or C infection, resolution of infection must be demonstrated by
             negative serology for hepatitis B surface antigen (HBsAg) and/or negative hepatitis C
             virus (HCV) RNA.

          -  Patients may not have uncontrolled HIV/AIDS infection. However, HIV positive patients
             on highly active retroviral therapy (HAART) with an undetectable viral load and CD4
             T-cell count above 200 may participate.

          -  Anticipated requirement for surgery during the study period or major surgery within 3
             weeks of initiating treatment.

          -  Active central nervous system (CNS) metastases or leptomeningeal involvement. Patients
             with known CNS metastases must have received definitive radiotherapy or surgery at
             least 4 weeks prior to initiating treatment with imaging demonstrating no progression
             of disease over this interval.