Phase I Sodium Selenite in Combination With Docetaxel in Castration-resistant Prostate Cancer

A Phase I Study Evaluating the Efficacy and Safety of Sodium Selenite in Combination With Docetaxel in Castration-resistant Prostate Cancer

Selenium, in the form of inorganic Sodium Selenite, may be useful for treating existing prostate cancer. This idea is based on data from our laboratory showing that 1) prostate cancer cells are more sensitive to Selenium (Sodium Selenite)-induced apoptosis than normal prostate epithelial cells, 2) Selenite induces significant growth inhibition of well established prostate cancer tumors in mice at doses that have no detectable toxicity, and 3) Selenite disrupts AR signaling, and that the inhibition of AR expression and activity by Selenite occurs via a redox mechanism involving GSH, superoxide, and Sp1. Altogether, these findings suggest that Selenium may be useful in a variety of potential indications in the natural history of prostate cancer, including both hormone sensitive and castrate resistant prostate cancer, as a single agent, or in combination with radiation, chemotherapy or conventional hormone therapy. Selenite is a potential novel inhibitor of AR expression and function in prostate cancer.

Study Overview

• Status: Terminated
• Conditions: Urologic Neoplasms; Prostate Cancer; Prostate Cancer Metastatic Disease
• Intervention / Treatment: Drug: Docetaxel; Drug: Biosyn; Drug: Prednisone

• Study Type: Interventional
• Enrollment (Actual): 2
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Stanford, California, United States, 94305
      • Stanford University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Histologically confirmed adenocarcinoma of the prostate

2. Castration-resistant prostate cancer requires the following 3 criteria:

   • Failure of first line bilateral orchiectomy or therapy with an LHRH agonist,
   • A rising PSA on 3 consecutive occasions at least 1 week apart (but not limited to the 30 day screening period), AND
   • A castrate level of testosterone (<50ng/dL)
3. PSA doubling time (PSADT) > 1 months
4. Failure on docetaxel chemotherapy as defined by a rising PSA .
5. A minimum PSA of 2 ng/mL
6. Age >=18 years
7. Life expectancy greater than 6 months
8. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 or Karnofsky performance status >=80%
9. Bone metastases will be allowed
10. The subject has a QTcB (Bazett corrected) or QTcF (Frederica corrected) < 470 msec.
11. Ability to understand and the willingness to sign a written informed consent document.
12. Willingness to stay on docetaxel chemotherapy despite rising PSA level.

Exclusion Criteria:1. Radiotherapy for prostate cancer within 28 days prior to Day 1.

2. More than 1 prior chemotherapy

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

• Absolute neutrophil count (ANC) < 1500/uL
• Platelet count <= 100 x 10^9/L
• Total bilirubin >= ULN
• AST, and/or ALT > 1.5 x the upper limit of normal (ULN) with a concomitant alkaline phosphastase >2.5 X ULN
• Serum creatinine > 2.0 mg/dL

• Hemoglobin < 9 g/dL

  4. 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.

  5. History of other malignancies within 5 years prior to Day 1 except for tumors with a negligible risk for metastasis or death, such as adequately controlled basal cell carcinoma, squamous-cell carcinoma of the skin, or early-stage bladder cancer

  6. Current, recent (within 4 weeks of the first infusion of this study), or planned participation in an experimental drug study.

  7. Known or prior treated brain metastases.

  8. History of hypersensitivity to docetaxel

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

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

  11. History of stroke or transient ischemic attack within 6 months prior to study enrollment 12. The subject is known to be positive for the human immunodeficiency virus (HIV) and is receiving antiretroviral 12. Willingness to stay on docetaxel chemotherapy despite rising PSA level.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: combination sodium selenite and docetaxel	Drug: Docetaxel; IV 75 mg/m2; Drug: Biosyn; IV dosage varies; Drug: Prednisone; 5mg, orally

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
To determine the safety and tolerability of the combination sodium selenite and docetaxel after 4 cycles of combination therapy using the NCI Common Toxicity Criteria v3.0 grading system for adverse events	after 4 cycles of combination therapy
To determine the maximum tolerated dose (MTD)	1 cycle

Collaborators and Investigators

• Sponsor: Sandy Srinivas

Study record dates

Study Major Dates

• Study Start: April 1, 2010
• Primary Completion (Actual): October 1, 2012
• Study Completion (Actual): October 1, 2012

Study Registration Dates

• First Submitted: June 30, 2010
• First Submitted That Met QC Criteria: July 1, 2010
• First Posted (Estimate): July 2, 2010

Study Record Updates

• Last Update Posted (Actual): March 15, 2017
• Last Update Submitted That Met QC Criteria: March 13, 2017
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Neoplastic Processes; Prostatic Neoplasms; Neoplasm Metastasis; Urologic Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Inflammatory Agents; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Docetaxel; Prednisone
• Other Study ID Numbers: PROS0033; SU-05122010-6002 (Other Identifier: Stanford University); 17356 (Other Identifier: REB)