Study of the Hypomethylating Drug Guadecitabine (SGI-110) Plus Cisplatin in Relapsed Refractory Germ Cell Tumors

Primary Objective:

To assess the safety and toxicity of guadecitabine (SGI-110) plus cisplatin including the
dose limiting toxicity (DLT) and to determine the Maximum tolerated dose (MTD)

Secondary Objective:

To assess the efficacy of guadecitabine (SGI-110) to resume sensitivity to cisplatin in
refractory GCT

Correlative Objective:

To evaluate the pharmacodynamic activity of guadecitabine (SGI-110) Evaluate miRNA biomarkers
in serum on day 1 of cycles 1-6

Intervention and Mode of Delivery: Guadecitabine (SGI-110) will be given subcutaneously,
daily, 30 mg/m2 on days (1-5) followed by cisplatin 100mg/m2 on day 8 every 4 weeks.

Duration of Intervention and Evaluation:

Treatment will be continued for a maximum of 6 cycles or until disease progression or
unacceptable toxicity whichever occurs first. Subjects who are responding to therapy without
major toxicty would be allowed to continue on single agent guadecitabine (SGI-110) at the MTD
after 4-6 cycles of the combination therapy until disease progression. Subjects will be
followed after the last cycle every 2 months for the 1st year, and every 4 months thereafter
until death (expected overall survival less than 12 months).

Inclusion Criteria:

1. ≥ 18 years old at the time of informed consent

2. Written informed consent and HIPAA authorization for release of personal health
information.

3. Subjects who are willing and able to comply with the protocol and study procedures
including willingness to undergo tumor biopsy for tumor cells before therapy at Cycle
1, Day 1, and Day 8 (before cisplatin dose) if this is clinically and safely feasible
to do so.

4. Subjects with histologically or serologically confirmed diagnosis of recurrent germ
cell tumor.

5. Subjects who have platinum-resistant disease. There is no limit on the number of prior
treatment regimens.

6. Subjects must have had prior high dose chemotherapy (HDCT) treatment when indicated.

7. Subjects who have measurable disease according to Response Evaluation Criteria in
Solid Tumors (RECIST) v1.1 or elevated Tumor markers (hCG or AFP).

Note: patients without measurable disease are allowed on the study as long as they
have clearly rising tumor markers and they will be exempt from biopsy.

8. Subjects with ECOG performance status of 0-2.

9. Subjects must be at least 3 weeks from last chemotherapy.

10. Females of childbearing potential must not be pregnant or breast-feeding. Male and
female patients of reproductive potential must agree to use two forms of highly
effective contraception from the screening visit through 30 days after the last dose
of study drug. Acceptable forms of effective contraception include:

- Oral, injected or implanted hormonal methods of contraception.

- Placement of an intrauterine device (IUD) or intrauterine system (IUS).

- Barrier methods of contraception: Condom or Occlusive cap (diaphragm or
cervical/vault caps) with spermicidal foam/gel/film/cream/suppository.

- Male sterilization (with the appropriate post-vasectomy documentation of the
absence of sperm in the ejaculate).

- True abstinence: When this is in line with the preferred and usual lifestyle of
the subject. [Periodic abstinence (e.g., calendar, ovulation, symptothermal,
post-ovulation methods) and withdrawal are not acceptable methods of
contraception.] Pregnancy tests for females of childbearing potential are
required; must be serum at screening and the post treatment safety assessment
visit. A positive urine pregnancy test must be confirmed by a serum pregnancy
test and a pelvic US since some NSGCT may secrete beta-hCG and cause a false
positive pregnancy. A pelvic US does not need to be repeated with each cycle
unless the treating physician thinks it is necessary to do so.

11. The following laboratory values must be obtained within 14 days prior to registration
for protocol therapy.

- Absolute neutrophil count ≥ 1500 cells/mm3

- Hemoglobin (Hgb) ≥ 8 g/dL

- Platelets count ≥ 100,000 cells/mm3

- Serum creatinine levels ≤ 1.5 mg/dl and calculated (by Cockcroft-Gault formula)
or measured creatinine clearance ≥ 50 mL/min

- Bilirubin ≤ 2 x ULN

- Aspartate aminotransferase (AST, SGOT) ≤ 3 x ULN

- Alanine aminotransferase (ALT, SGPT) ≤ 3 x ULN

Exclusion Criteria:

1. Active central nervous system (CNS) metastases. Subjects with neurological symptoms
should undergo a head CT scan or brain MRI to exclude brain metastasis, at the
discretion of the treating physician.

NOTE: A subject with prior brain metastasis may be considered if they have completed
their treatment for brain metastasis, no longer require corticosteroids, and are
asymptomatic.

2. Treatment with any investigational agent within 30 days prior to registration for
protocol therapy.

3. Concurrent participation in a clinical trial which involves another investigational
agent.

4. Subjects with Grade 2 or greater neuropathy.

5. Subjects with a life-threatening illness, medical condition or organ system
dysfunction, or other reasons which, in the Investigator's opinion, could compromise
the subject's safety, interfere with or compromise the integrity of the study outcomes
including incomplete recovery from the acute effects from any prior anti-neoplastic
therapy.

6. Pregnancy or breast-feeding.