RNR Inhibitor COH29 in Treating Patients With Solid Tumors That Are Refractory to Standard Therapy or For Which No Standard Therapy Exists

PRIMARY OBJECTIVES:

I. To determine the maximum tolerated dose of COH29 (ribonucleotide reductase [RNR] inhibitor
COH29) and recommended dose for further phase II testing.

II. To determine the pharmacokinetics of COH29.

SECONDARY OBJECTIVES:

I. To characterize the safety and tolerability of COH29 by assessing toxicities per Common
Terminology Criteria for Adverse Events (CTCAE) version 4.0.

II. To characterize any clinical activity of COH29 via objective tumor response.

III. To assess pharmacodynamic response of COH29 on ribonucleotide reductase (RR) and
poly-adenosine diphosphate-ribose polymerase (PARP) activity in peripheral blood mononuclear
cells (PBMCs).

IV. To explore baseline RRM2 tumor protein expression as a potential correlative marker for
COH29 response.

V. To explore measurement of plasma cytokeratin 18 (CK18) as a surrogate pharmacodynamic
marker of COH29 antitumor activity.

OUTLINE: This is a dose escalation study.

Patients receive RNR inhibitor COH29 orally (PO) twice daily (BID) on days 1-21. Courses
repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 30 days.

Inclusion Criteria:

- All patients must have the ability to understand and the willingness to sign a written
informed consent

- Life expectancy of greater than 3 months by physician assessment

- Eastern Cooperative Oncology Group (ECOG) performance status =< 2

- Patients must have histologically or cytologically confirmed (at original diagnosis or
subsequent recurrence or progression) solid tumor that is metastatic, unresectable,
progressive, or recurrent, and for which standard curative or palliative measures do
not exist or are no longer effective

- Patients must have measurable or evaluable disease

- Patients must not have received prior chemotherapy or radiation for < 4 weeks prior to
start of study treatment

- Patients may be entered if they have received prior radiation therapy involving =< 30%
of the bone marrow; any prior radiation therapy must have been administered >= 4 weeks
prior to start of study treatment and the patient must be recovered from the acute
toxic effects of the treatment prior to start of study treatment

- Patients may be enrolled with a history of treated brain metastases that are
clinically stable for >= 4 weeks prior to start of study treatment

- Women of child-bearing potential and men must agree to use adequate contraception
(hormonal or barrier method of birth control or abstinence) prior to study entry and
for six months following duration of study participation; women of child-bearing age
will undergo urine pregnancy testing prior to study enrollment; should a woman become
pregnant or suspect that she is pregnant while participating on the trial, she should
inform her treating physician immediately

- Active breast-feeding is also not allowed on study enrollment

- Leukocytes >= 3,000 cells/µL

- Absolute neutrophil count >= 1,500 cells/µL

- Platelets >= 100, 000 cells/µL

- Total bilirubin =< 1.5 times the upper limit of normal (ULN)

- Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 2.5 x ULN; AST/ALT
=< 5 x ULN if liver metastasis is present

- Serum creatinine =< 1.5 mg/dL or a measured creatinine clearance >= 50 mL/min

- Prothrombin time (PT)/international normalized ratio (INR)/ activated partial
thromboplastin time (aPTT) =< 1.5 x ULN

- Negative serum beta-human chorionic gonadotropin (HCG) test (female patient of
childbearing potential only)

Exclusion Criteria:

- Patients may not be receiving any other investigational agents; use of
over-the-counter herbal medications will also be excluded

- Patients with uncontrolled undercurrent illness including, but not limited to, ongoing
or active infection, or psychiatric illness/social situations that would limit
compliance with study requirements

- Patients unable or unwilling to swallow pills

- Active heart disease including myocardial infarction within previous 3 months,
symptomatic coronary artery disease or heart block, or uncontrolled congestive heart
failure

- Patients with a history of noninfectious pneumonitis will be excluded during the
dose-escalation phase of the trial

- Patients, who in the opinion of the investigator and another independent party, may
not be able to adhere to the safety monitoring requirements of the study