| Eligibility |
- INCLUSION CRITERIA:
Patients must:
- Have recurrent or refractory/unresectable disease for which there is no known curative
therapy.
---Wild type-gastrointestinal stromal tumors (GIST): Patients with recurrent or
progressive disease will be eligible. Newly diagnosed patients with resectable
localized disease will not be eligible. Newly diagnosed patients with metastatic
disease and newly diagnosed patients with residual tumor following surgical debulking
will be eligible.
- Paraganglioma-Pheochromocytoma (PHEO/PGL): Patients with recurrent or progressive
disease will be eligible. Newly diagnosed patients with PHEO/PGL that is
metastatic at diagnosis and/or unresectable will be eligible Patients with
PHEO/PGL with localized (non-metastatic), resectable disease will not be
eligible.
- Renal cell cancer associated with HLRCC: Patients with localized, resectable
HLRCC-associated renal cell cancer will not be eligible. Patients with metastatic
and/or unresectable Hereditary leiomyomatosis and renal cell cancer
(HLRCC)-associated renal cell cancer will be eligible.
- Have one of the following confirmed histologically, cytologically, or through
biochemical testing:
- wild-type GIST (GIST without KIT or platelet derived growth factor receptor alpha
(PDGFRA) mutation);
- PHEO/PGL with a germline mutation in Succinate Dehydrogenase Complex Flavoprotein
Subunit A (SDHA), Succinate Dehydrogenase Complex Flavoprotein Subunit B (SDHB),
SDHC, or SDHD;
--renal cell cancer associated with HLRCC.
- Testing will be performed in Clinical Laboratory Improvement Amendments (CLIA)
certified labs using genetic tests for KIT/PDGFRA and testing panels developed for
patients with PHEO/PGL. Results from outside labs will be accepted. Pathologic
diagnosis will be reviewed and verified at the Clinical Center.
- Age: be greater than or equal to 12 years of age
Because there is no dosing or adverse event data currently available on the use of SGI-110
in children < 18 year of age, children < 12 years of age will be excluded from this study,
but may be eligible for future pediatric trials should the results of the study be
positive.
- Measurable disease:
Have measurable disease, defined as at least one lesion that can be accurately measured in
at least one dimension (longest diameter to be recorded for non-nodal lesions and short
axis for nodal lesions) as greater than or equal to 20 mm with conventional techniques or
as greater than 10 mm with spiral computed tomography (CT) scan.
- Prior Therapy
- Prior therapy requirements:
---Wt-GIST: Because there are no standard chemotherapy regimens known to be effective
for wt-GIST, previously untreated participants are eligible.
--PHEO/PGL with germline SDH subunit mutation: 131I-MIBG in patients with MIBG avid
tumors or cytotoxic chemotherapy (cyclophosphamide, vincristine, and dacarbazine (CVD)
or temozolomide) is required prior to enrollment on this trial. However, patients who
have refused cytotoxic chemotherapy or for whom treatment on this protocol prior to
receiving cytotoxic chemotherapy is felt to be in the best interest for the patient by
the local investigator will also be eligible.
---HLRCC-associated renal cell cancer: Because there are no standard chemotherapy
regimens known to be effective for HLRCC-associated renal cell cancer, previously
untreated participants are eligible.
- Prior therapy wash-out period requirements
--Participants must be at least 4 weeks from prior surgical procedures and surgical
incisions must be healed.
---Participants must have had their last fraction of external beam radiation therapy
at least 4 weeks prior to enrollment. Participants with prior radiation therapy must
be at least 4 weeks post therapy and have had progression of disease outside the
radiation port.
- Participants must have had their last dose of cytotoxic chemotherapy at least 28
days prior to enrollment, their last dose of biological therapy, such as
biological response modifiers (e.g., cytokines), immunomodulatory agents,
vaccines, differentiating agents, used to treat their cancer at least 28 days
prior to enrollment, their last dose of a monoclonal antibody at least 28 days
prior to enrollment, and their last dose of any investigational agent at least 28
days prior to enrollment.
- Participants must have recovered from the acute toxic effects of prior therapy to
a grade 1 level prior to enrollment (does not apply to alopecia).
- Performance Level: Eastern Cooperative Oncology Group (ECOG) performance status less
than or equal 2 or Karnofsky greater than or equal to 60% in patients greater than 16
years of age, Lansky greater than or equal to 60 for patients less than or equal to 16
years of age.
- Have normal organ and marrow function as defined below:
- absolute neutrophil count greater than or equal to 1,500/mcL
- platelets greater than or equal to 100,000/mcL
- total bilirubin within normal institutional limits
- Aspartate aminotransferase (AST) Serum glutamic oxaloacetic
transaminase(SGOT)/Alanine aminotransferase (ALT) Serum glutamic pyruvic
transaminase(SGPT) less than or equal to 2.5 x institutional upper limit of
normal
- creatinine within normal institutional limits
OR
----creatinine clearance greater than or equal to 60 mL/min/1.73 m^2 for patients with
creatinine levels above institutional normal.
-Birth Control:
The effects of SGI-110 on the developing human fetus are unknown. For this reason and
because decitabine is known to be teratogenic, women of child-bearing 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, and for 6
months following 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.
-Ability of subject or legal guardians (if the patient is <18 years old) to understand and
the willingness to sign a written informed consent document.
EXCLUSION CRITERIA:
Patients with any one the following will be excluded:
- Ongoing radiation therapy, chemotherapy, hormonal therapy directed at the tumor,
immunotherapy, or biologic therapy, including investigational agents for their
disease.
- History of allergic reactions to SGI-110 or decitabine.
- Uncontrolled intercurrent illness including, but not limited to, symptomatic
congestive heart failure, unstable angina pectoris, cardiac arrhythmia, symptomatic
pulmonary disease or psychiatric illness/social situations that would limit compliance
with study requirements.
- Pregnant or breastfeeding
Pregnant women are excluded from this study because SGI-110 is a derivative of decitabine
which has the potential for teratogenic or abortifacient effects. Because there is an
unknown but potential risk for adverse events in nursing infants secondary to treatment of
the mother with SGI-110, breastfeeding should be discontinued if the mother is treated with
SGI-110.
These potential risks may also apply to other agents used in this study.
- Any evidence of severe or uncontrolled systemic disease, active infection, active
bleeding diatheses, or renal transplant, including any patient known to have hepatitis
B, hepatitis C, or human immunodeficiency virus (HIV) will be excluded. Patients with
HIV who have adequate cluster of differentiation 4 (CD4) count, not requiring
antiretroviral medication, may be enrolled.
- Patients who, in the opinion of the investigator, may not be able to comply with the
safety monitoring requirements of the study.
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