Ilorasertib in Treating Patients With CDKN2A-deficient Advanced or Metastatic Solid Cancers That Cannot Be Removed by Surgery
Ilorasertib in Treating Patients With CDKN2A-deficient Advanced or Metastatic Solid Cancers That Cannot Be Removed by Surgery
This pilot phase I trial studies how well ilorasertib works in treating patients with
 cyclin-dependent kinase inhibitor 2A (CDKN2A)-deficient solid cancers that have spread to
 other places in the body and usually cannot be cured or controlled with treatment (advanced)
 or have spread to other places in the body (metastatic) and cannot be removed by surgery.
 Ilorasertib may stop the growth of tumor cells by blocking some of the enzymes needed for
 cell growth.
Inclusion Criteria:

 -  Eligible and consent to the Institutional Review Board (IRB) 13-0002 registry trial
 protocol

 -  Subjects must have histologically confirmed solid malignancy that is metastatic or
 unresectable

 -  The patient should have received all established therapies where there is a clear,
 superior available regimen available for the patient and the patient should have
 demonstrated progressive disease on or since completion of the last treatment regimen

 -  Patients must have measurable disease defined as lesions that can be accurately
 measured in at least one dimension (longest diameter to be recorded) as >= 2 cm with
 conventional techniques or as >= 1 cm with spiral CT scan

 -  Patients must have prior CT scan images available for investigators to collect

 -  Patients must have available tumor molecular profiling from Clinical Laboratory
 Improvement Amendments (CLIA)-certified labs or have available archived tissue to be
 sent to such a laboratory in the context of this investigation

 -  Molecular testing in a CLIA-certified laboratory must have demonstrated a deletion
 involving the CDKN2A locus or a mutation within the locus that can be deemed from best
 available evidence to be likely to cause inactivation of a gene within or protein
 encoded by CDKN2A; sequencing or fluorescence in situ hybridization (FISH)/chromogenic
 in situ hybridization (CISH) methods are acceptable; the investigators will consider
 analyses performed according to similar standards as applied by Foundation Medicine
 (likely to be the most common source of molecular diagnostic data for patients in this
 trial)

 -  At least 3 weeks must have passed since any prior anti-tumor therapies including
 chemotherapy, radiation therapy or any other anti-cancer treatments

 -  Serum creatinine value of < 1.5 times the upper limit of normal (ULN) and either an
 estimated creatinine clearance value of > 50 mL/min as determined by the Chronic
 Kidney Disease Epidemiology (CKD EPI) or MDRD (Modification of Diet in Renal Disease)
 formulae or a creatinine clearance value of > 50 mL/min based on a 24 hour urine
 collection

 -  Subject has adequate liver function as demonstrated by serum bilirubin < 2 x ULN and
 Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x ULN. For
 subjects with liver metastasis, adequate liver function is demonstrated by serum
 bilirubin =< 2 x ULN and AST/ALT =< 5.0 x ULN

 -  Subject has adequate bone marrow as demonstrated by absolute neutrophil count (ANC) >=
 1,500/mm^3 (1.5 x 10^9/L); platelets >= 100,000/mm^2 (100 x 10^9/L); hemoglobin >= 9.0
 g/dL (1.4 mmol/L)

 -  Subject has QTc interval < 500 msec on baseline electrocardiogram

 -  Subject has blood pressure controlled to < 150 mmHg systolic and < 95 mmHg diastolic
 at screening

 -  Subject has a documented left ventricular ejection fraction > 50%

 -  Women of child-bearing potential and men must agree to use adequate contraception (one
 of the following listed below) prior to the study entry, for the duration of study
 participation and up to 3 months following completion of therapy; women of
 child-bearing potential must have a negative pregnancy test within 7 days prior to
 initiation of treatment and post-menopausal women must be amenorrheic for at least 12
 months to be considered of non-childbearing potential

 -  Acceptable contraception

 -  Total abstinence from sexual intercourse (minimum one complete menstrual
 cycle)

 -  Vasectomized male subjects or vasectomized partner of female subjects

 -  Double-barrier method (condoms, contraceptive sponge, diaphragm or vaginal
 ring with spermicidal jellies or cream)

 -  Additionally, male subjects (including those who are vasectomized) whose
 partners are pregnant or might be pregnant must agree to use condoms for the
 duration of the study and for 3 months following completion of therapy

 -  Eastern Cooperative Oncology Group (ECOG) performance status: 0-1

 -  Patients must be able to provide written informed consent

 Exclusion Criteria:

 -  Patients with hospitalization within 4 weeks of treatment initiation date for
 co-morbid conditions or any complication of disease or therapy that is deemed by the
 principal investigator as unstable or incompletely treated

 -  Patients with any psychiatric or social condition that leads them to be unlikely to
 adhere to the study schedule and contribute to the primary objectives

 -  Women that are pregnant or lactating are excluded from this study

 -  Subject has known active central nervous system (CNS) involvement; the subject has
 untreated brain or meningeal metastases; CT scans are not required to rule out brain
 or meningeal metastases unless there is a clinical suspicion of central nervous system
 disease; subjects with treated brain metastases that are radiographically or
 clinically stable for at least 4 weeks after therapy and have no evidence of
 cavitation or hemorrhage in the brain lesion(s) are eligible, providing that they are
 asymptomatic, and do not require corticosteroids (must have discontinued steroids at
 least 1 week prior to study drug administration)

 -  Subject has had major surgery within 28 days prior to study day 1

 -  Subject has proteinuria defined by the National Cancer Institute Common Terminology
 Criteria for Adverse Events (NCI CTCAE version [v] 4.0) grade > 1 at baseline as
 measured by a urine dipstick (2+ or greater) and confirmed by a 24 hour urine
 collection (>= 1 g/24 hrs); subjects may be re-screened if proteinuria is shown to be
 controlled with or without intervention

 -  Subject is taking any oral anticoagulant

 -  History of:

 -  Symptomatic congestive heart failure

 -  Unstable angina pectoris or cardiac arrhythmia (subjects with stable atrial
 fibrillation are not excluded)

 -  Adrenal insufficiency

 -  Subject is unable to swallow or absorb oral tablets normally

 -  Subject takes cytochrome P450, family 3, subfamily A (CYP3A) inhibitors within 3 days
 or inducers within 7 days prior to the study drug administration; any questions or
 clarifications of these determinations should be brought to the attention of the
 principal investigator (PI); the PI will make the final determination on when it is
 safe to initiate ABT-348 (ilorasertib) therapy under circumstances where the magnitude
 or relevance of possible CYP3A4 inhibitors/inducers is unclear in the protocol
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