Clinical Trials /

Sitravatinib in Advanced Liposarcoma and Other Soft Tissue Sarcomas

NCT02978859

Description:

The purpose of this study is to evaluate Sitravatinib, an oral small molecular receptor tyrosine kinase inhibitor, for the treatment of advanced liposarcoma.

Related Conditions:
  • Alveolar Rhabdomyosarcoma
  • Alveolar Soft Part Sarcoma
  • Dedifferentiated Liposarcoma
  • Malignant Peripheral Nerve Sheath Tumor
  • Synovial Sarcoma
  • Well Differentiated Liposarcoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Sitravatinib in Advanced Liposarcoma and Other Soft Tissue Sarcomas
  • Official Title: A Phase II Trial of Sitravatinib (MGCD516), a Multi-receptor Tyrosine Kinase Inhibitor, in Advanced Liposarcoma and Other Soft Tissue Sarcomas

Clinical Trial IDs

  • ORG STUDY ID: AAAQ8661
  • NCT ID: NCT02978859

Conditions

  • Liposarcoma
  • Metastatic Liposarcoma

Interventions

DrugSynonymsArms
MGCD516SitravatinibMGCD516

Purpose

The purpose of this study is to evaluate Sitravatinib, an oral small molecular receptor tyrosine kinase inhibitor, for the treatment of advanced liposarcoma.

Detailed Description

      Sarcomas are a group of cancers which arise from connective tissue and bone, of which more
      than 50 subtypes exist. Approximately 12,000 people are diagnosed with sarcoma annually in
      the United States.

      Liposarcoma is one of the more common types of soft tissue sarcoma. The primary treatment for
      liposarcoma is surgery when possible. When liposarcoma is not amenable to surgery, various
      systemic treatments, including chemotherapy, are used. However, the effectiveness of existing
      treatments for liposarcoma is limited.

      Sitravatinib is an oral, targeted drug which inhibits receptor tyrosine kinases. Receptor
      tyrosine kinases are proteins on the surface of the liposarcoma cell which play a role in
      cancer growth. In laboratory work, Sitravatinib effectively suppressed the growth of
      liposarcoma models. The purpose of this study is to evaluate the safety and efficacy of
      Sitravatinib in patients with liposarcoma which cannot be removed by surgery.
    

Trial Arms

NameTypeDescriptionInterventions
MGCD516ExperimentalPatients with locally advanced and unresectable or metastatic sarcoma will receive MGCD516 at the discretion of the principal investigator until disease progression, unacceptable toxicity or adverse event(s) or withdrawal of consent.
  • MGCD516

Eligibility Criteria

        Inclusion Criteria:

          -  Stage 1, histologically confirmed well-differentiated or de-differentiated
             liposarcoma. If stage 1 of the Simon II stage design fails to meet its endpoint for
             liposarcoma patients, an additional 16 patients will be enrolled, composed of 4 each
             of MPNST, synovial sarcoma, alveolar rhabdomyosarcoma and alveolar soft part sarcoma
             (otherwise, an additional 16 patients with well-differentiated or de-differentiated
             liposarcoma would be enrolled). 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.

          -  Patients must evidence of disease progression, either clinically or
             radiographically,within the 8 weeks prior to study enrollment, as determined by the
             principal investigator.

          -  Patients must have been treated with at least one prior systemic regimen for sarcoma.
             Adjuvant systemic therapy qualifies as prior therapy for the purposes of this study.
             There is no upper limit on previous lines of therapy received. A prior line of
             systemic therapy may include prior investigational agents received as part of other
             clinical studies.

          -  Patients must be age 18 years or older. Because no dosing or adverse event data are
             currently available for MGCD516 in patients less than 18 years of age, children are
             excluded from the present study, but will be eligible for future pediatric trials.

          -  Patients must demonstrate an Eastern Cooperative Oncology Group (ECOG) performance
             status of 0 or 1.

          -  Patients must demonstrate normal organ and marrow function.

          -  Patients must demonstrate adequately controlled blood pressure at the time of study
             entry, as defined by a blood pressure ≤ 150/100 mmHg at study screening on at least
             one of two screenings conducted at least 24 hours apart. If blood pressure meets these
             guidelines on initial measurement, no subsequent measurement for screening is needed.
             Blood pressure may be assessed by automated or manual methods by an appropriately
             trained clinician or nurse.

          -  Patients must have normal left ventricular systolic function, as demonstrated by a
             transthoracic echocardiogram or multigated acquisition (MUGA) scan showing a normal
             left ventricular ejection fraction.

          -  Women of child-bearing potential and all 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.

          -  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 28 days preceding
             study registration. Patients may not have received treatment with nitrosureas or
             mitomycin within the 42 days prior to study registration. Patients may not have
             received treatment with a small molecule targeted agent (including off-label or
             investigational use) within 14 days preceding study registration, 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 registration.

          -  Patients may not be receiving any other investigational agent for any purpose
             concurrently. Patients may not require ongoing treatment with (a) gastric pH modifying
             medications including proton pump inhibitors or H2 blockers (patients may switch to
             antacids), (b) medications which are known to be sensitive substrates or substrates
             with a narrow therapeutic index for the P-gp and breast cancer resistance protein
             (BCRP) transporters and/or (c) medications known to cause corrected QT Interval (QTc)
             prolongation with risk of Torasades. Please see Appendix 1 for a list of such
             prohibited concomitant medications at study entry.

          -  Patients with brain metastases which are symptomatic may not be enrolled. Those
             subjects with untreated brain metastases ≤ 1 cm may who are asymptomatic and for whom
             there are no plans for surgery, radiation or corticosteroid use may be considered
             eligible at the discretion of the principal investigator. Subjects with brain
             metastases that have been treated and are stable for at least 1 month are eligible if
             they are asymptomatic and not receiving corticosteroids.

          -  Patients may not have a history of allergic reaction or hypersensitivity to
             microcrystalline cellulose (Avicel PH302) or polysorbate 80 (Tween 80), which are
             components of the drug product MGCD516.

          -  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, uncontrolled diabetes mellitus or
             uncontrolled psychiatric illness that would limit compliance with study requirements
             in the opinion of the principal investigator. Additionally, patients must be free of
             any impairment in the ability to swallow and absorb the oral study drug.

          -  Patients may not be pregnant or nursing. Pregnant women are excluded from this study
             because the teratogenic effects of MGCD516 have not been adequately studied. A
             negative pregnancy test must be documented 7 days or less prior to registration.
             Because there is an unknown but potential risk for adverse events to nursing infants
             secondary to treatment of the mother with MGCD516, breastfeeding must be discontinued
             prior to registration for this clinical trial.

          -  Patients may not have known HIV infection. HIV-positive patients on combination.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression free rate
Time Frame:12 weeks
Safety Issue:
Description:To assess the efficacy of MGCD516 in patients with advanced liposarcoma by evaluating the progression free rate at 12 weeks as compared historical controls.

Secondary Outcome Measures

Measure:Adverse event rate
Time Frame:12 weeks
Safety Issue:
Description:To evaluate the safety profile of MGCD516.
Measure:Overall response rate
Time Frame:Up to 33 months
Safety Issue:
Description:To assess the efficacy of MGCD516 in patients with advanced liposarcoma.
Measure:Progression free survival rate
Time Frame:Up to 33 months
Safety Issue:
Description:To assess the efficacy of MGCD516 in patients with advanced liposarcoma.
Measure:Overall survival rate
Time Frame:Up to 33 months
Safety Issue:
Description:To assess the efficacy of MGCD516 in patients with advanced liposarcoma.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Matthew Ingham

Trial Keywords

  • MGCD516
  • Sarcoma
  • Liposarcoma
  • Unresectable Liposarcoma
  • Metastatic Liposarcoma
  • Sitravatinib

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