PT-112 in Advanced Solid Tumors

Study Groups:

If participant is found to be eligible to take part in this study, they will be assigned to
a study group based on when they joined this study. Up to 4 groups of 3-6 participants will
be enrolled in the dose escalation portion of the study. Up to 4 groups of 15 participants
with the same tumor type will be enrolled in the dose confirmation portion.

If participant is enrolled in the dose escalation portion, the dose of PT-112 they receive
will depend on when they joined this study. The first group of participants will receive
the lowest dose level of PT-112. Each new group will receive a higher dose of PT-112 than
the group before it, if no intolerable side effects were seen. This will continue until the
highest tolerable dose of PT-112 is found.

If participant is assigned to a lower dose and a higher dose is found to be safe, they may
be moved to the higher dose level.

If participant is enrolled in the dose confirmation portion, they will receive PT-112 at the
highest dose that was tolerated in the dose escalation portion.

Study Drug Administration:

Participant will receive PT-112 by vein over about 60 minutes on Days 1, 8, and 15 of each
28-day study cycle.

Study Visits:

On Day 1 of Cycles 1 and 2:

- Participant will have a physical exam (Cycle 2 only).

- Participant will have an EKG before, during, and 30 minutes after their dose of study
drug.

- Blood (about 2 teaspoons) will be drawn for routine tests and to check how well
participant's blood clots.

- Blood (about 2 teaspoons) will be drawn for tumor marking testing.

- Urine will be collected for routine tests, including a pregnancy test if participant is
able to become pregnant.

- If participant is in the dose escalation portion of this study, blood (about 1 teaspoon
each time) will be drawn at 13 different time points over 24 hours for pharmacokinetic
(PK) testing during Day 1 of Cycle 1 and at 3 different time points during Day 1 of
Cycle 2 over 4 hours. PK testing measures the amount of study drug in the blood at
different time points.

At the beginning of each cycle, participant will be contacted by phone about 24-48 hours
after their first dose of study drug and asked if they are having any side effects related
to the nervous system, such as numbness, tingling, cold-induced discomfort, and muscle
spasms. The phone call should last about 15 minutes.

On Days 8 and 15 of Cycles 1 and 2:

- Participant will have a physical exam (Cycle 1/Day 8 and Cycle 2/Day 15 only).

- Participant will have an EKG before, during, and 30 minutes after their dose of study
drug. (Day 15 only)

- Blood (about 2 teaspoons) and urine will be collected for routine tests.

- If participant is in the dose escalation portion of this study, blood (about 1 teaspoon
each time) will be drawn at 13 different time points over the 24 hours for PK testing
on Day 8 of Cycle 1 and at 3 different time points over 4 hours on Day 15 of Cycle 1
and Days 8 and 15 of Cycle 2.

On Day 22 of Cycles 1 and 2:

- Blood (about 2 teaspoons) will be drawn for routine tests.

- On Day 22 of Cycle 1 only, urine will be collected for routine tests.

On Day 1 of Cycles 3-6:

- Participant will have a physical exam (Day 1 of Cycles 4 and 6 only).

- Participant will have an x-ray, CT scan, PET scan, or MRI scan to check the status of
the disease (Cycle 3/Day 1 and Cycle 5/Day 1 only).

- Participant will have an EKG to check their heart function.

- Blood (up to 3 teaspoons) will be drawn for routine tests and to check how well
participant's blood clots.

- Urine will be collected for routine tests, including a pregnancy test if participant is
able to become pregnant.

- Blood (about 2 teaspoons) will be drawn for tumor marker testing.

- Participant will have a CT scan, MRI scan, or chest x-ray to check the status of the
disease.

On Days 8, 15, and 22 of Cycles 3-6, blood (about 1-2 teaspoons) will be drawn for routine
tests.

Length of Study:

Participant may continue taking the study drug for up to 6 cycles. Participant will no
longer be able to take the study drug if the disease gets worse, if intolerable side effects
occur, or if they are unable to follow study directions.

Patient's participation on the study will be over after the end-of-treatment visit.

End-of-Treatment Visit:

About 30 days after participant's last dose of study drug, they will have an
end-of-treatment visit. At this visit, participant will have the following tests and
procedures performed:

- Participant will have a physical exam.

- Participant will have an EKG.

- Blood (up to 3 teaspoons) will be drawn for routine tests and to check how well
participant's blood clots.

- Urine will be collected for routine tests, including a pregnancy test if participant is
able to become pregnant.

This is an investigational study. PT-112 is not FDA approved or commercially available. It
is currently being used for research purposes only. The study doctor can explain how the
study drug is designed to work.

Up to 84 participants will be enrolled in this multicenter study. Up to 28 participants
will take part at MD Anderson.

Inclusion Criteria:

1. Males and females >/=18 years of age

2. Pathologically confirmed advanced solid tumor for which standard therapy proven to
provide clinical benefit does not exist or is no longer effective

3. Eastern Collaborative Oncology Group (ECOG) Performance Status of
4. Evaluable disease, either measurable on physical examination or imaging by Response
Evaluation Criteria in Solid Tumors (RECIST v1.1), or by informative tumor marker(s)

5. Laboratory values at the Screening Visit: a. Absolute neutrophil count (ANC)
>/=1,500/mm3; b. Platelets >/=100,000/mm3; c. Total bilirubin limit of normal (ULN) (subjects with Gilbert's Syndrome are allowed if direct
bilirubin is within normal limits); d. Aspartate aminotransferase (AST [serum
glutamate oxaloacetate transaminase (SGOT])) aminotransferase (ALT serum glutamate pyruvate transaminase (SGPT])) ULN; f. Serum albumin >/=3.0 gm/dL; g. Serum creatinine creatinine clearance >/= 60 mL/min; and h. Negative serum beta-human chorionic
gonadotropin (hCG) test in women of childbearing potential (defined as women years of age, or >50 years of age with a history of amenorrhea for to study entry)

6. Subjects with primary liver cancer or hepatic metastasis are eligible to enroll,
provided that, at the Screening Visit, the following criteria are met: a. Total
bilirubin is no higher than the ULN; b. AST and ALT are each Severe liver dysfunction (Child-Pugh Class B or C) is not present; and d. Subjects
with a history of esophageal bleeding have varices that have been sclerosed or banded
and no bleeding episodes have occurred during the prior 6 months

7. If there is a known history of brain metastases, either treated with radiation
therapy or untreated, the metastatic disease must be stable in the judgment of the
Principal Investigator and must not require ongoing treatment with corticosteroids or
anticonvulsants and individual lesion size must not exceed 2 cm in longest dimension

8. Willing and able to provide written Informed Consent and comply with the requirements
of the study

9. Additional Inclusion Criteria during the Dose Confirmation Phase 1. Selected tumor
type, as determined by experience during the Dose Escalation Phase; 2. Measurable
disease, using RECIST v1.1

Exclusion Criteria:

1. Any cytotoxic chemotherapy within 21 days prior to initiation of study drug

2. Any immunomodulatory drug therapy, anti-neoplastic hormonal therapy (unless dose has
been stable for 3 months prior to Baseline and will remain stable during the trial),
immunosuppressive therapy, corticosteroids >20 mg/day prednisone or equivalent
(unless administered to prevent contrast material reactions during radiographic
procedures), or growth factor treatment (e.g., erythropoietin) within 14 days prior
to initiation of study drug

3. Presence of an acute or chronic toxicity of prior chemotherapy, with the exception of
alopecia, that has not resolved to Institute CTCAE v 4.0

4. Evidence of peripheral neuropathy of any grade within 28 days prior to initiation of
dosing

5. Receipt of more than 3 prior regimens of cytotoxic chemotherapy for metastatic
disease unless prior approval is granted by the Sponsor

6. Bone marrow reserve which, in the clinical judgment of the Principal Investigator, is
not adequate for participation in this trial

7. Known allergy or hypersensitivity to platinum-containing agents, or known intolerance
to a prior platinum-containing agent which, in the judgment of the Principal
Investigator, precludes re-exposure to a platinum-containing agent

8. Radiotherapy within 28 days prior to baseline

9. Receipt of radiotherapy to >25 % of bone marrow

10. Major surgery within 28 days prior to initiation of study drug

11. Life expectancy <12 weeks

12. Active or clinically unstable bacterial, viral, or fungal infection requiring
systemic therapy

13. Known human immunodeficiency virus or acquired immunodeficiency syndrome-related
illness

14. Clinically significant hearing impairment, as judged by the Principal Investigator

15. Any of the following within 3 months prior to initiation of study drug: uncontrolled
congestive heart failure (New York Heart Association Classification 3 or 4), angina,
myocardial infarction, cerebrovascular accident, coronary/peripheral artery bypass
graft surgery, transient ischemic attack, or pulmonary embolism

16. Unstable cardiac dysrhythmias or persistent prolongation of the corrected QT interval
(QTc) (Fridericia) interval to >450 msec for males or >470 msec for females

17. Previous malignancy, except for non-squamous-cell carcinoma of skin or
carcinoma-in-situ of the uterine cervix, unless the tumor was treated with curative
intent more than 2 years prior to study entry

18. Use of any investigational agents within 28 days of baseline

19. Pregnant or lactating female

20. Women of childbearing potential, unless they agree to use dual contraceptive methods
which, in the opinion of the Principal Investigator, are effective and adequate for
that subject's circumstances while on study drug and for 3 months afterward

21. Men who partner with a woman of childbearing potential, unless they agree to use
effective, dual contraceptive methods (i.e., a condom, with female partner using
oral, injectable, or barrier method) while on study drug and for 3 months afterward

22. Any severe, acute, or chronic medical or psychiatric condition, or laboratory
abnormality that may increase the risk associated with study participation or study
drug administration, may interfere with the informed consent process and/or with
compliance with the requirements of the study, or may interfere with the
interpretation of study results and, in the Investigator's opinion, would make the
subject inappropriate for entry into this study

23. Until the results of the bridging toxicology study are submitted to the sites: Body
surface area such that the dose would exceed 100 mg of PT-112/dose