A Phase 1 Dose-Escalation and Pharmacokinetic Study of NC-4016 in Patients With Advanced Solid Tumors or Lymphoma

Study Groups:

If you are found to be eligible to take part in this study, you will be enrolled in either a
dose escalation group or the dose expansion group.

Dose Escalation:

If you are in a dose escalation group, you will be assigned to a dose level based on when
you joined this study. Up to 6 dose levels of NC-4016 will be tested and at least 3 patients
will be enrolled at each dose level. The first group of participants will receive the lowest
dose level of NC-4016. Each new group will receive a higher dose of NC-4016 than the group
before it, if no intolerable side effects were seen. This will continue until the highest
tolerable dose of NC-4016 is found.

Dose Expansion:

If you are in the dose expansion group, you will receive NC-4016 at the highest dose that
was tolerated in the escalation groups.

Study Drug Administration:

Each study cycle is 21 days.

On Day 1 of each cycle, you will receive NC-4016 by vein over 2 hours.

You will be given standard drugs to help decrease the risk of side effects. You may ask the
study staff for information about how the drugs are given and their risks.

If you have a severe side effect, your dose of study drug may be delayed.

Study Visits:

On Day 1 of each cycle:

- You will have a physical exam.

- Your vital signs (blood pressure, heart rate, breathing rate, and temperature) will be
monitored every 20 minutes during the infusion and 1 hour after the end of the infusion
during Cycle 1 and right before and at the end of the infusion for all other cycles.

- Blood (about 3 teaspoons) will be drawn for routine tests.

- You will have a neurological exam and electromyogram.

- You will have an EKG before the start of the infusion, at the end of the infusion, and
1 hour after the end of the infusion (Cycle 1 and 2 only). After Cycle 1, you will only
have 1 EKG before dosing.

On Days 8 and 15 of each cycle, blood (about 3 teaspoons) will be drawn for routine tests.

On Day 2 of Cycle 1 you will have an EKG corresponding to the 24 hour PK testing.

Every 3 cycles (every 9 weeks):

- You will have an x-ray, CT, MRI, or PET scan to check the status of the disease.

- If you have lymphoma, you will have a bone marrow biopsy to check the status of the
disease.

- You will have a nerve conduction evaluation.

- If the doctor thinks it is needed, blood (about 1 teaspoon) will be drawn for tumor
marker testing.

PK Testing:

Blood (about 1 teaspoon each time) will be drawn for pharmacokinetic (PK) testing. PK
testing measures the amount of study drug in the body at different time points.

- On Day 1 of Cycles 1 and 3, blood will be drawn before, then at 0.5, 1, and 2 hours
during the infusion, and then 9 more times up to 12 hours after you receive the study
drug (13 draws total each day).

- On Days 2, 3, 4, 6, 8, and 15 of Cycles 1 and 3, blood will be drawn 1 time after you
receive the study drug.

- On Day 1 of Cycles 2 and Cycle 4, blood will be drawn 1 time before you receive the
study drug.

Urine Collection:

Urine will be collected for PK testing at the following time points during Cycles 1 and 3:

- Before you receive the study drug

- 0-2 hours (during the infusion)

- 2-4 hours after you received the study drug

- 4-8 hours after you received the study drug

- 8-12 hours after you received the study drug

- 12-24 hours after you received the study drug

You will collect your urine at home over 24 hours during the following times after you
received the study drug:

- Days 1-2

- Days 2-3

- Days 7-8

- Days 14-15

- Days 21-22

Your study doctor will provide you with urine collection bottles. Your urine samples will
contain a very small amount of platinum from the study drug. This is not considered to be a
risk to you, but as a precaution, the urine collection containers should only be handled by
you, and the containers will be labeled as a "Bio-Hazard".

If you have a severe side effect, you may have extra tests until the side effects have
gotten better.

Length of Study:

You may continue taking the study drug for as long as you are benefitting. You will be taken
off study early if the disease gets worse, intolerable side effects occur, you develop new
health problems, your doctor thinks that it is no longer in your best interest to receive
the study drug, or if you are unable to follow study directions.

Your participation on the study will be over after the end-of-dosing visit.

End-of-Dosing Visit:

Within 28 days after the last dose of NC-4016:

- You will have a physical exam.

- You will have a neurological exam and an electromyogram.

- You will have a chest x-ray.

- You will have an x-ray, CT scan, MRI scan, or PET scan, or a bone marrow biopsy if you
have lymphoma, to check the status of the disease.

- Blood (about 3 teaspoons) and urine will be collected for routine tests.

- You will have an EKG and an ECHO or MUGA.

- If the doctor thinks it is needed, blood (about 1 teaspoon) will be drawn for tumor
marker testing.

This is an investigational study. NC-4016 is not commercially available or FDA approved. It
is currently being used for research purposes only. The study doctor can explain how NC-4016
is designed to work.

Up to 40 participants will be enrolled in this study. All will be enrolled at MD Anderson.

Inclusion Criteria:

1. Have signed written informed consent prior to the initiation of any study-specific
procedures

2. Be a male or female 18 years or older

3. Have a histologically or cytologically confirmed diagnosis of advanced solid tumor or
lymphoma, or primitive hepatocarcinoma with radiological diagnosis

4. Have advanced or metastatic disease refractory to standard curative or palliative
therapy or contraindication to standard therapy

5. Have an ECOG performance status of 0-2

6. Have adequate bone marrow reserve: a. Absolute neutrophil count at least 1.5 x
10^9/L, b. Platelet count at least 100 x 10^9/L, and c. Hemoglobin at least 10 g/L
(transfusion is allowed to achieve hemoglobin of 10 g/L)

7. Have adequate liver function: a. Total serum bilirubin no more than 1.5 x upper limit
of normal (ULN), and b. Alanine aminotransferase and aspartate aminotransferase<= 2.5
x ULN or <= 5.0 x ULN in case of documented hepatic metastasis

8. Have adequate renal function: glomerular filtration rate >=50 mL/min (calculated
according to the formula of Cockcroft and Gault)

9. Be reasonably recovered from preceding major surgery as judged by the investigator or
no major surgery within 4 weeks prior to the start of Day 1 treatment

10. Have a negative pregnancy test for females at screening, preferably done within 1
week before Day 1 of treatment (not applicable to patients with bilateral
oophorectomy and/or hysterectomy)

11. Be willing to abstain from heterosexual activity or practice physical barrier
contraception from study entry to 6 months after the last day of treatment

Exclusion Criteria:

1. Have peripheral neuropathy of Grade 3 or Grade 4 at screening, according to National
Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE)v4.03, 14
June 2010 scale; or TNSc score greater than 4

2. Have an interval from previous neurotoxic platinums of less than 6 months and/or from
previous other neurotoxic drugs less than 3 months (eg, taxanes) unless reasonably
recovered from all grades of neurotoxicity as judged by the investigator

3. Have a history of thrombocytopenia with complications including hemorrhage or
bleeding >= Grade 2 using NCI CTCAE v4.03, 14 June 2010 that required medical
intervention or any hemolytic condition or coagulation disorders that would make
participation unsafe in the opinion of the investigator

4. Have unresolved toxicity from previous treatment or previous investigational agents;
excluding alopecia. Clinical judgment by the investigator is allowed to determine if
grade 1 fatigue at screening is residual toxicity from prior treatment or is a
symptom of the patient's general condition or disease. The investigator and medical
monitor will discuss the eligibility of patients with baseline toxicity

5. Have known hypersensitivity to Pt compounds

6. Have received investigational agents or systemic anticancer agents (other than
neurotoxic compounds) within 14 days of Day 1 of treatment, or 28 days for those
agents with unknown elimination half-lives, or known elimination half-lives greater
than 50 hours; or 6 weeks for mitomycin C or for nitrosourea agents

7. Is pregnant or breast-feeding

8. Have signs or symptoms of end organ failure, major chronic illnesses other than
cancer, or any severe concomitant conditions which, in the opinion of the
investigator, make it undesirable for the patient to participate in the study, or
which could jeopardize compliance with the protocol

9. Have experienced any of the following within the 6-month period prior to screening:
angina pectoris, coronary artery disease or cerebrovascular accident, transient
ischemic attack, cardiac failure with known ejection fraction less than 40%, or
cardiac arrhythmia requiring medical therapy

10. Have known hepatitis B or C, or human immunodeficiency virus infection

11. Is unwilling or unable to comply with study procedures, or is planning to take a
vacation for 7 or more consecutive days during the treatment phase of the study