| Eligibility |
Inclusion Criteria:
- Male or female at least 18 years of age.
- Histologically or cytologically confirmed, measurable (defined as those that could be
accurately measured in a least 1 dimension with a longest diameter =20 mm using
conventional techniques or =10 mm with spiral computed tomography scan) or evaluable
solid malignancy (with the exception of primary central nervous system [CNS] tumors)
per RECIST 1.1. Scans performed within 1 month of starting study drug will be
accepted.
- Received at least one systemic therapy for advanced disease, with no further approved
treatment options that provide proven clinical benefit.
- Eastern Cooperative Oncology Group (ECOG) performance status =2.
- Females of childbearing potential who are sexually active with a nonsterilized male
partner agree to use 2 methods of effective contraception from screening, and agree to
continue using such precautions for 90 days after the final dose of study drug;
cessation of birth control after this point should be discussed with a responsible
physician. Periodic abstinence, the rhythm method, and the withdrawal method are not
acceptable methods of birth control.
- Nonsterilized males who are sexually active with a female of childbearing potential
must agree to use an acceptable method of effective contraception from Day 1 and for
90 days after the final dose of study drug.
- Female subjects of childbearing potential must be nonpregnant, nonlactating, and have
a negative pregnancy test result at Screening and Day 1 of Cycles 1-6.
- Able to provide written, informed consent before initiation of any study related
procedures, and is able, in the opinion of the Investigator, to comply with all the
requirements of the study.
- Able to swallow oral medication.
- Subject has the following laboratory values at Screening:
1. Absolute neutrophil count =1500/mm3
2. Platelet count =100,000/mm3
3. Hemoglobin =9.0 g/dL (must be >2 weeks post-red blood cell transfusion)
4. Bilirubin =1.5x the upper limit of normal (ULN). For subjects with documented
Gilbert's disease, bilirubin =3.0 mg/dL. For subjects with documented liver
metastases, bilirubin = 2.5x ULN.
5. Serum creatinine =1.5x the ULN or creatinine clearance (CrCl) =50 mL/min.
6. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =3x the ULN
(=5x the ULN for subjects with liver metastases)
Exclusion Criteria:
- Subject has an abnormal electrocardiogram (ECG) that, in the Investigator's opinion,
is clinically significant and would preclude study participation.
- Subject has QT interval corrected (QTc) >480 ms (both males and females) at Screening
(repeat values may be obtained during the period between Screening and admission to
the study site).
- Subject has any surgical or medical condition (active or chronic) that may interfere
with drug absorption, distribution, metabolism, or excretion of the study drug, or any
other condition that may place the subject at risk for such interference (for example,
short bowel syndrome or inflammatory bowel disease).
- Subject has a history of Type 1 Diabetes (T1D) or is considered at high risk for T1D,
where high risk is defined as
1. Subject has 1 first-degree relative (FDR; defined as parents, offspring or
siblings) with T1D AND A1C value > 6.5% or
2. Subject has 2+FDR with T1D
- Subject has uncontrolled hypertension, defined as a blood pressure reading >160/100
mmHg, despite maximum antihypertensive therapy.
- Subject has received:
1. Radionuclide treatment within 6 weeks of the first dose of study drug in this
study
2. Local palliative radiation therapy (XRT) (small port) =2 weeks before first dose
of study drug
3. Treatment with therapeutic doses of metaiodobenzylguanidine (MIBG) =6 weeks
before first dose of study drug
4. Prior total body irradiation, total craniospinal XRT, or =50% radiation of pelvis
within 6 months of receiving first dose of study drug
5. Treatment with a monoclonal antibody within 28 days or 5 half-lives, whichever is
shorter, from treatment with first dose of study drug
6. Therapy with a growth factor within 7 days of starting study drug
7. Chemotherapy within 3 weeks of starting study drug (6 weeks if prior nitrosourea)
8. Subjects receiving systemic (oral or parenteral) corticosteroid therapy within 7
days of first dose of study drug or a requirement for chronic systemic
immunosuppressive therapy for any reason. Topical or inhaled steroids are
allowed.
- Subject has not fully recovered to baseline or National Cancer Institute Common
Terminology Criteria for Adverse Events (NCI-CTCAE) = Grade 1 from toxicity due to all
prior therapies, except alopecia and other non-clinically significant AEs.
- Subject has any history of human immunodeficiency virus (HIV) or immunodeficiency at
Screening.
- Subject has a diagnosis of chronic active hepatitis B or C.
- Subject has uncontrolled intercurrent illness including, but not limited to ongoing or
active bacterial, fungal, or viral infection requiring intravenous therapy (not
prophylaxis) at the time of study enrollment, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that would limit compliance with
study requirements.
- Subject has a history of a major adverse cardiac event, including cerebrovascular
accident or myocardial infarction within the prior 6 months, or uncontrolled
congestive heart failure (New York Heart Association class 3 or 4) at Screening.
- Subject has active, suspected, or previously documented autoimmune disease, defined as
requiring systemic treatment.
- Subject has known or suspected history of retinitis pigmentosa or known or suspected
familial history of retinitis pigmentosa.
- Subject has prothrombin time/International Normalized Ratio or partial thromboplastin
time test results at screening =1.5 x ULN.
- Subject requires concomitant treatment, in therapeutic doses, with anticoagulants such
as warfarin-related agents, thrombin or FXa inhibitors, or antiplatelet agents (eg,
clopidogrel). Low-dose aspirin (=81 mg/day), low-dose warfarin (=1 mg/day), and
prophylactic low molecular weight heparin are permitted.
- Subject had surgery (excluding line insertions) within 1 month of the first dose of
study drug or has lingering wound complications.
- Subject is unable or unwilling to abide by the study protocol or cooperate fully with
the Investigator or designee.
|
