Slow recruitment and lack of efficacy despite the completion of several dose steps.

The purpose of this study is to evaluate the safety and tolerability of the investigational drug VLX600 in patients with refractory advanced solid tumors.

This Phase I, open label dose escalation study of VLX600 in patients with refractory advanced solid tumors will determine the safety profile and maximum tolerated dose (MTD) of VLX600 when administered by intravenous infusion on Days 1, 8, and 15 of each 28-day treatment cycle. Dose escalation will proceed according to the standard "3 + 3" design using doubling doses. The doses are: 10, 20, 40, 80, 160, and 210 mg VLX600.

Inclusion Criteria:

1. Men and women greater than or equal to 18 years of age.

2. Histologic evidence of advanced solid tumors (excluding central nervous system (CNS) primary tumors) non-resectable, refractory to standard therapies, or patient cannot receive or refuses standard therapy.

3. Solid tumors measurable according to RECIST 1.1 or solid tumors not measurable according to RECIST 1.1, but which express tumor markers (e.g., prostate cancer with prostate specific antigen (PSA) expression or ovarian cancer with cancer antigen-125 (CA-125) expression) are eligible.

4. Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1.

5. Must have the following laboratory values, obtained less than or equal to 7 days prior to registration:

   • Absolute neutrophil count (ANC) greater than or equal to 1500/µL
   • Platelet (PLT) count greater than or equal to 100,000/µL
   • Total bilirubin less than 1.5 x upper normal limit (UNL)
   • Aspartate aminotransferase (AST) (SGOT) less than or equal to 3 x UNL
   • Creatinine less than 1.5 x UNL

6. Women of childbearing potential must have a negative serum pregnancy test less than or equal to 7 days prior to registration.

7. Life expectancy greater than 12 weeks.

8. Must provide written informed consent.

9. Must be willing to return to Mayo Clinic enrolling institution for follow-up.

Exclusion Criteria:

1. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, diabetes mellitus, seizure disorder or psychiatric illness/social situations that would limit compliance with study requirements.

2. Treatment with any of the following prior therapies:

   • Chemotherapy less than or equal to 4 weeks prior to registration
   • Mitomycin C/nitrosoureas less than or equal to 6 weeks prior to registration
   • Immunotherapy less than or equal to 4 weeks prior to registration
   • Biologic therapy less than or equal to 4 weeks prior to registration
   • Radiation therapy less than or equal to 4 weeks prior to registration
   • Non-cytotoxic therapy less than or equal to 5 half-lives prior to registration

3. Failure to fully recover from acute, reversible effects of prior chemotherapy regardless of interval since last treatment.

4. Major surgery less than 28 days prior to study entry.

5. Active other malignancy, except non-melanoma skin cancer or carcinoma-in-situ (e.g., of cervix, breast, prostate). If there is a history of prior malignancy, patient must not be receiving other specific treatment (other than hormonal therapy) for the cancer.

6. CNS metastases if not previously treated and stable for at least 2 months per imaging and clinical assessment.

7. Any of the following because this study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown:

   • Pregnant women
   • Nursing women
   • Men or women of childbearing potential unwilling to employ adequate contraception

8. Other concurrent chemotherapy, immunotherapy, radiotherapy, any ancillary therapy considered investigational (utilized for a non-FDA-approved indication and in the context of a research investigation) or receiving any other investigational agent which would be considered as a treatment for the primary neoplasm.

9. Cardiac issues consisting of either symptomatic congestive heart failure (NYHA Class II or higher), unstable angina pectoris, myocardial infarction within 6 months, and/or cardiac arrhythmia, including atrial fibrillation (which is symptomatic or requires treatment).

10. Corrected QT interval (QTc) interval greater than 450 msec (males) or greater than 470 msec (females).

11. Immunocompromised patients (other than that related to the use of corticosteroids) including patients with a known history of human immunodeficiency virus (HIV) or active infection with hepatitis B virus (HBV) or hepatitis C virus (HCV).

12. Clinically relevant retinal abnormalities as per the medical history or ophthalmologic findings in the pretreatment evaluation (e.g., retinitis pigmentosa or macular degeneration).

13. History of thromboembolism within the past 5 years, history of catheter-related thrombophlebitis or other clinically significant thrombophlebitis are excluded.