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

This study has been terminated.
Sponsor:
Information provided by (Responsible Party):
Sandy Srinivas, Stanford University
ClinicalTrials.gov Identifier:
NCT01155791
First received: June 30, 2010
Last updated: January 25, 2013
Last verified: January 2013
  Purpose

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.


Condition Intervention Phase
Urologic Neoplasms
Prostate Cancer
Prostate Cancer Metastatic Disease
Drug: Docetaxel
Drug: Biosyn
Drug: Prednisone
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Study Evaluating the Efficacy and Safety of Sodium Selenite in Combination With Docetaxel in Castration-resistant Prostate Cancer

Resource links provided by NLM:


Further study details as provided by Stanford University:

Primary Outcome Measures:
  • 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 [ Time Frame: after 4 cycles of combination therapy ] [ Designated as safety issue: Yes ]
  • To determine the maximum tolerated dose (MTD) [ Time Frame: 1 cycle ] [ Designated as safety issue: Yes ]

Enrollment: 2
Study Start Date: April 2010
Study Completion Date: October 2012
Primary Completion Date: October 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: combination sodium selenite and docetaxel Drug: Docetaxel
IV 75 mg/m2
Drug: Biosyn
IV dosage varies
Drug: Prednisone
5mg, orally

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01155791

Locations
United States, California
Stanford University School of Medicine
Stanford, California, United States, 94305
Sponsors and Collaborators
Sandy Srinivas
Investigators
Principal Investigator: Dr. Sandy Srinivas Stanford University
  More Information

No publications provided

Responsible Party: Sandy Srinivas, Associate Professor, Stanford University
ClinicalTrials.gov Identifier: NCT01155791     History of Changes
Other Study ID Numbers: PROS0033, SU-05122010-6002, 17356
Study First Received: June 30, 2010
Last Updated: January 25, 2013
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Additional relevant MeSH terms:
Prostatic Neoplasms
Neoplasm Metastasis
Urologic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases
Neoplastic Processes
Pathologic Processes
Docetaxel
Sodium Selenite
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Trace Elements
Micronutrients
Growth Substances
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on September 18, 2014