| Eligibility |
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.
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