SOR-C13 in Treating Patients With Advanced Refractory Solid Tumors

PRIMARY OBJECTIVES:

I. To define the maximum tolerated doses (MTD) of TRPV6 calcium channel inhibitor SOR-C13
(SOR-C13) in subjects with advanced solid tumor cancers of epithelial origin.

II. To define the safety profiles of the treatment.

SECONDARY OBJECTIVES:

I. To evaluate clinical response signals to the treatment. II. To assess predictive
biomarkers (baseline molecular mutation status) and/or resistant pathways by comparing
molecular signatures at baseline versus at time of relapse in patients who have achieved
objective responses.

OUTLINE: This is a dose-escalation study.

Patients receive TRPV6 calcium channel inhibitor SOR-C13 intravenously (IV) over 2 hours on
days 1, 2, 8, 9, 15, 16, 22, and 23. Courses repeat every 28 days in the absence of disease
progression or unacceptable toxicity.

Inclusion Criteria:

- Subjects with a histologic diagnosis of solid tumor cancers of epithelial origin
(metastatic epithelial ovarian, pancreatic and prostate cancers are preferred since
these tumor types have TRPV6 overexpression)

- Subjects with advanced refractory cancer for which standard curative or palliative
measures do not exist or are no longer effective. There is no limitation on the number
or types of prior therapy

- Patients must have measurable or evaluable disease, as defined by Response Evaluation
Criteria in Solid Tumors 1.1 (RECIST1.1)

- Women of child-bearing potential (who are not postmenopausal for at least one year or
are not surgically sterile) and men must agree to use adequate contraception (e.g.,
hormonal, barrier device, or abstinence) prior to study entry, for the duration of
study participation, and for 30 days after the last dose the study agents

- Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of
0 to 1

- Neutrophils >= 1,500 /uL

- Platelets >= 100,000 /uL

- Total bilirubin =< 1.5 x ULN (upper limit of normal) (except patients with Gilbert's
syndrome, who must have a total bilirubin =< 3.0 mg/dL)

- Alanine aminotransferase (ALT) =< 2.5 x ULN or =< 5 x ULN if liver metastases persist

- Serum creatinine =< 1.5 x ULN or calculated creatinine clearance >= 45 mL/minute by
the Cockcroft-Gault method

- Albumin >= 3.0 g/dL (>= 3.0 g/L)

- International normalized ratio (INR) (international normalized ratio) =< 1.4

- Patients should be able to read and fully understand the requirements of the trial, be
willing to comply with all trial visits and assessments, and be willing and able to
sign an Institutional Review Board (IRB)-approved written informed consent document

- Subjects must have recovered from major infections and/or surgical procedures and, in
the opinion of the investigator, not have a significant active concurrent medical
illness precluding protocol treatment

- Patients agree to provide archival tissue block or 10 formalin-fixed paraffin-embedded
(FFPE) slides paraffin for use in pharmacodynamics correlative studies

Exclusion Criteria:

- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection requiring intravenous antibiotics, symptomatic congestive heart failure (New
York Heart Association [NYHA] class III or IV), or history of myocardial infarction,
unstable angina, stroke or transient ischemic attack within 6 months prior to study
enrollment

- History of clinically significant allergic reactions to the study drugs or their
analogs, or any component of the products

- Any treatment specific for systemic tumor control within 3 weeks prior to the
initiation of the study drugs; or within 2 weeks if cytotoxic agents were given weekly
(within 6 weeks for nitrosoureas or mitomycin C), or within 5 half-lives for targeted
agents with half-lives and pharmacodynamic effects lasting less than 4 days, or
failure to recover from toxic effects of any therapy prior to the study drug treatment

- Patients who have not recovered from major surgical procedure, or significant
traumatic injury (i.e., still need additional medical care for these issues)

- History of any of the following cardiovascular events or conditions within the past 6
months prior to enrollment: myocardial infarction, unstable angina, cerebrovascular
accident or transient ischemic attack, New York Heart Association class >= II chronic
heart failure, hypokalemia, significant arrhythmia

- Corrected QC (QTc) interval > 430 msec or use of drugs that prolong the QT
interval at screening; family history of long QT syndrome

- Significant arrhythmias are defined as symptoms of syncope or severe palpitations
(palpitations requiring referral to cardiac monitoring), or electrocardiography
(ECG) findings of supraventricular tachycardia (including atrial fibrillation or
atrial flutter) or ventricular tachycardia (including ventricular fibrillation)
or ventricular ectopy (ventricular premature depolarization)

- Clinically significant and uncontrolled major medical condition(s) that places the
subject at an unacceptably high risk for toxicities. These include, but are not
limited to: active infections, symptomatic pulmonary disease, inadequate pulmonary
function, seizure disorder, or psychiatric illness

- Current use of more than one antihypertensive medication

- For patients receiving antihypertensive medication: systolic blood pressure < 120 mm
Hg and/or diastolic blood pressure < 70 mm Hg at screening

- A known diagnosis of human immunodeficiency virus (HIV) infection or acquired immune
deficiency syndrome (AIDS), acute or chronic hepatitis B or hepatitis C infection, as
determined by medical history

- Major surgical procedure within 4 weeks prior to enrollment

- Lactating or pregnant female

- Females of childbearing potential and males not using adequate birth control

- Current treatment or treatment within 4 weeks of screening with bisphosphonates

- Hypocalcemia at screening

- History of acute pancreatitis within 6 months prior to screening

- Known hypoparathyroidism, pseudohypoparathyroidism, or vitamin D deficiency, or
clinical evidence of other conditions known to associated with hypocalcemia, including
hypoalbuminemia, hyperphosphatemia, hypomagnesemia

- Current treatment or treatment within 4 weeks of screening with drugs known to reduce
serum calcium levels, including: bisphosphonates, antiepileptic drugs, cinacalcet,
macrolide antibiotics (such as erythromycin, azithromycin), large doses of
corticosteroids (> 20 mg/day of prednisone or equivalent), or any IV use of
corticosteroids. In addition, long-term use (defined as ongoing use for >= 4 weeks) of
corticosteroids within 8 weeks of screening is prohibited

- Symptomatic and uncontrolled metastasis to the central nervous system or
leptomeningeal or lymphangitic carcinomatosis

- Grade 2 or higher peripheral neuropathy

- Known human immunodeficiency virus infection (HIV), active hepatitis B or C