Sodium Selenite and Radiation Therapy in Treating Patients With Metastatic Cancer

A Phase I Study Evaluating the Efficacy and Safety of Sodium Selenite in Combination With Palliative Radiation Therapy in Patients With Metastatic Cancer

The purpose of this study is to determine the maximum-tolerated dose (MTD) of sodium selenite when administered in combination with radiation therapy to subjects with metastatic cancer based on safety and tolerability.

Primary Objectives:

• To determine the maximum tolerated dose (MTD) of sodium selenite when given in combination with palliative radiation therapy
• To assess the safety and tolerability of the combination of sodium selenite and palliative radiation therapy in metastatic cancer

Secondary Objectives:

• To assess the pharmacokinetics of sodium selenite
• To evaluate the anti tumor activity of sodium selenite and palliative radiation therapy when given in combination

OUTLINE:

Patients receive sodium selenite orally (PO) 2 hours before daily radiation therapy treatments. Treatment continues for the duration of the course of radiation therapy in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 2 months.

Inclusion criteria:

1. Histologically confirmed adenocarcinoma of the prostate from a prostate biopsy or prostatectomy specimen (primary site), or histological confirmation of adenocarcinoma /carcinoma in a metastatic site of disease in the setting of elevated PSA and imaging consistent with metastatic prostate cancer, or history of prostate cancer with documented metastasis, or histologically confirmed other solid tumor malignancy, multiple myeloma, or plasmacytoma with pathological confirmation of metastasis
2. Metastatic cancer requiring palliative radiation therapy
3. For patients with metastatic prostate cancer, PSA ≥ 2 ng/mL, except for patients who have recently started androgen deprivation therapy with PSA < 2 ng/mL
4. Age ≥18 years
5. Life expectancy greater than 3 months
6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 or Karnofsky performance status ≥ 80%
7. QT interval corrected using Fridericia's method (QTcF) < 460 msec (see Appendix C for Fredericia's criteria).
8. Ability to understand and the willingness to sign a written informed consent document

Exclusion criteria:

1. Inadequate organ function, as evidenced by any of the following at screening:

   • Absolute neutrophil count (ANC) < 1500/µL
   • Platelet count ≤ 100 x 109/L
   • Serum creatinine > 2.0 mg/dL
   • Total bilirubin > 1.5 x upper limit of normal (ULN)
   • AST, and/or ALT > 2 x ULN
   • Hemoglobin < 9 g/dL

2. Men with reproductive potential who do not agree to use an accepted and effective method of contraception during the study treatment period and for at least 3 months after completion of the study treatment

3. History of other malignancies within 5 years prior to Day 1 except for tumors that in the opinion of the investigators have a negligible risk for metastasis or death, such as (but not exclusively) adequately controlled basal cell carcinoma, squamous cell carcinoma of the skin, or early stage bladder cancer

4. Current, or recent (within 4 weeks of the first treatment of this study) cytotoxic chemotherapy (eg, cisplatin, taxol) or experimental drug therapy, or planned participation in an experimental drug study

5. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, significant vascular disease (eg, aortic aneurysm, aortic dissection), symptomatic peripheral vascular disease, or psychiatric illness/social situations that would limit compliance with study requirements

6. History of myocardial infarction or unstable angina within 6 months prior to study enrollment

7. History of stroke or transient ischemic attack within 6 months prior to study enrollment

8. The subject is known to be positive for the human immunodeficiency virus (HIV) and is receiving antiretroviral therapies. Subjects known to be HIV positive who do not require antiretroviral therapy will be eligible if they meet other entry criteria

9. Women who are pregnant or breastfeeding

10. Inability to comply with study and/or follow up procedures