A Phase 1b Dose Escalation Trial of PSK®/Placebo With Docetaxel to Treat Metastatic Castration-resistant Prostate Cancer

This study has suspended participant recruitment.
(administrative hold until funding is secured)
Sponsor:
Collaborators:
University of Washington
Fred Hutchinson Cancer Research Center
Information provided by (Responsible Party):
Bastyr University
ClinicalTrials.gov Identifier:
NCT01685489
First received: September 6, 2012
Last updated: October 7, 2013
Last verified: October 2013

September 6, 2012
October 7, 2013
May 2013
August 2014   (final data collection date for primary outcome measure)
  • Determine tolerability dose of PSK alone and in combination with docetaxel [ Time Frame: 42 days ] [ Designated as safety issue: Yes ]
    Adverse events are graded to determine a dose limiting toxicity of PSK during the lead-in PSK alone and during the docetaxel treatment in combination with PSK.
  • Determine maximum tolerated dose and recommended phase 2 dose of PSK in combination with docetaxel [ Time Frame: 106 days ] [ Designated as safety issue: Yes ]
    When the maximum tolerated dose is determined, a total of 15 patients will be treated with the recommended phase 2 dose with the combination of docetaxel chemotherapy.
  • Maximum tolerated dose of PSK in combination with docetaxel [ Time Frame: 112 days ] [ Designated as safety issue: Yes ]
    Adverse events are graded to determine a dose limiting toxicity of PSK during the lead-in PSK alone and during the docetaxel treatment in combination with PSK.
  • Recommended phase 2 dose of PSK in combination with docetaxel [ Time Frame: 112 days ] [ Designated as safety issue: Yes ]
    When the maximum tolerated dose is determined, a total of 15 patients will be treated with the recommended phase 2 dose with the combination of docetaxel chemotherapy.
Complete list of historical versions of study NCT01685489 on ClinicalTrials.gov Archive Site
  • Pharmacokinetics of docetaxel when combined with oral PSK [ Time Frame: 106 days ] [ Designated as safety issue: No ]
    The plasma docetaxel levels are analyzed at eight time points during the cycle 1 of standard intravenous docetaxel at 75 mg/m2 with oral PSK/Placebo. After the seven-day washout of PSK/placebo at the cycle 3, the plasma docetaxel levels are analyzed again at eight time points during the cycle 4 of docetaxel treatment without PSK/Placebo.
  • Pharmacokinetics of oral PSK dosing and in combination with docetaxel [ Time Frame: 106 days ] [ Designated as safety issue: No ]
    The serum PSK levels are analyzed at two time points during the lead-in cycle and eight time points during the cycle 1 of standard intravenous docetaxel at 75 mg/m2 with oral PSK/Placebo. After the seven-day washout of PSK/placebo at the cycle 3, the plasma docetaxel levels are analyzed again at eight time points during the cycle 4 of docetaxel treatment without PSK/Placebo.
  • Immunological laboratory analysis [ Time Frame: 106 days ] [ Designated as safety issue: No ]
    Natural Killer (NK) cell functional activity, distributions of NK, B, and T cells, and IFN-gamma and TNF-alpha production capacity are analyzed and compared to those of the placebo group.
  • Clinical tumor markers [ Time Frame: 106 days ] [ Designated as safety issue: Yes ]
    Circulating tumor cell (CTC) and prostate specific antigen (PSA) levels are compared to that of the placebo group during the oral PSK lead-in period and during the combination therapy with docetaxel and PSK.
  • Prostatic acid phosphatase [ Time Frame: 106 ] [ Designated as safety issue: Yes ]
    The serum level of prostatic acid phosphatase levels are compared to that of the placebo group during the oral PSK lead-in period and during the combination therapy with docetaxel and PSK.
  • Pharmacokinetics of docetaxel when combined with oral PSK [ Time Frame: 112 days ] [ Designated as safety issue: No ]
    The plasma docetaxel levels are analyzed at eight time points during the cycle 1 of standard intravenous docetaxel at 75 mg/m2 with oral PSK/Placebo. After the seven-day washout of PSK/placebo at the cycle 3, the plasma docetaxel levels are analyzed again at eight time points during the cycle 4 of docetaxel treatment without PSK/Placebo.
  • Immunological laboratory analysis [ Time Frame: 112 days ] [ Designated as safety issue: No ]
    Natural Killer (NK) cell functional activity, distributions of NK, B, and T cells, and IFN-gamma and TNF-alpha production capacity are analyzed and compared to those of the placebo group.
  • Prostate specific antigen (PSA) [ Time Frame: 112 days ] [ Designated as safety issue: Yes ]
    Serum prostate specific antigen levels are compared to that of the placebo group during the oral PSK lead-in period and during the combination therapy with docetaxel and PSK.
  • Circulating tumor cells (CTC) [ Time Frame: 112 days ] [ Designated as safety issue: Yes ]
    Circulating tumor cell levels are compared to that of the placebo group during the oral PSK lead-in period and during the combination therapy with docetaxel and PSK.
  • Prostatic acid phosphatase [ Time Frame: 112 ] [ Designated as safety issue: Yes ]
    The serum level of prostatic acid phosphatase levels are compared to that of the placebo group during the oral PSK lead-in period and during the combination therapy with docetaxel and PSK.
Not Provided
Not Provided
 
A Phase 1b Dose Escalation Trial of PSK®/Placebo With Docetaxel to Treat Metastatic Castration-resistant Prostate Cancer
A Phase 1b Dose Escalation Trial of PSK®/Placebo With Docetaxel to Treat Metastatic Castration-resistant Prostate Cancer

This is a phase 1b study that follows a 3+3 dose escalation design and consists of a 21-day lead-in period of oral Polysaccharide Krestin (PSK)/placebo (study drug) alone followed by the addition to study drug of standard intravenous docetaxel at 75 mg/m2 every 3 weeks for three cycles. Study drug will be discontinued on day 15 of the third docetaxel cycle to allow for a 7-day washout period before the fourth dose of docetaxel. Pharmacokinetic (PK) analysis of docetaxel will be conducted during docetaxel cycle 1 (combination therapy) and cycle 4 (docetaxel alone). Serum for future PSK PK analysis will be collected on days 1, 3, and 15 of PSK/placebo lead-in and during cycles 1 and 4.

Not Provided
Interventional
Phase 1
Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Prostatic Neoplasms
  • Drug: Docetaxel, PSK®
    Other Names:
    • Polysaccharide-K
    • Krestin
    • Polysaccharide-Kureha
  • Drug: Docetaxel, Placebo
  • Experimental: Docetaxel, PSK®
    A 21-day lead-in oral PSK alone is followed by the addition of standard intravenous docetaxel at 75 mg/m2 evey 3 weeks for three cycles. After the third dose of docetaxel, study drug will be discontinued on day 14 to allow for a 7-day washout period before a fourth dose of docetaxel is administered.
    Intervention: Drug: Docetaxel, PSK®
  • Placebo Comparator: Docetaxel, Placebo
    A 21-day lead-in oral placebo alone is followed by the addition of standard intravenous docetaxel at 75 mg/m2 every 3 weeks for three cycles. After the third dose of docetaxel, the placebo will be discontinued on day 14 to allow for a 7-day washout period before a fourth dose of docetaxel is administered.
    Intervention: Drug: Docetaxel, Placebo

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Suspended
30
August 2014
August 2014   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Male patients 18 years or older
  • Histologically confirmed diagnosis of adenocarcinoma of the prostate
  • Evidence of metastatic disease by standard imaging studies (bone scan, Computerized Tomography Scan (CT) or Magnetic Resonance Imaging (MRI))
  • Testosterone levels <50 ng/dL
  • Confirmed progressive disease defined by one or more of the following:

    • an increase in PSA, > 2ng/dL x 2 or more values at least 1 week apart in the setting of metastatic disease
    • appearance of new bone lesions on bone scan
    • progression of soft tissue lesion defined by the Response Evaluation Criteria In Solid Tumors [RECIST] 1.1 criteria
  • Concurrent use of an agent for testosterone suppression (e.g., Luteinizing Hormone Releasing Hormone [LHRH] agonist) if the patient is not surgically castrate
  • Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 determined within 28 days before enrollment
  • Recovery to CTCAE grade ≤ 1 toxicity, to patient's baseline status (except alopecia), or toxicities deemed irreversible from the effects of prior cancer therapy (CTCAEs grade > 1 that are not considered a safety risk by the investigator will be allowed)
  • Adequate bone marrow function defined as:

    • absolute neutrophil count (ANC) > 1500 cells/mm³ without growth factor support
    • platelet count > 100,000 cells/mm³ without transfusion or growth factor support
    • hemoglobin > 9g/dL without transfusion or growth factor support
  • Adequate liver function defined as:

    • total bilirubin < upper limit of normal (ULN)
    • alanine aminotransferase (ALT) < 1.5 x ULN
    • aspartate aminotransferase (AST) < 1.5 x ULN
  • Adequate renal function defined as serum creatinine level within normal limits (WNL)
  • At least a 6-month or greater life expectancy
  • Ability to understand and sign a written informed consent, which will be obtained from study participants before undergoing any study-specific procedures
  • Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other trial procedures
  • Suitable venous access for the study-required blood sampling (i.e., including PK sampling)

Exclusion Criteria:

  • Prior treatment with antineoplastic chemotherapy or radioisotopes for metastatic disease
  • Prior adjuvant or neo-adjuvant chemotherapy within 12 months of study entry
  • Last dose of sipuleucel-T therapy within 4 weeks of enrollment
  • Any investigational therapies within 4 weeks of study entry
  • Radiotherapy within 4 weeks of study entry
  • Major surgery within 4 weeks of study entry, and not fully recovered to baseline or a stable clinical status
  • Uncontrolled high blood pressure (systolic blood pressure > 160mmHg, diastolic blood pressure > 95mmHg)
  • Receiving chronic steroid therapy. Topical and inhaled steroids are permitted
  • Known severe hypersensitivity reactions to docetaxel or other drugs formulated in polysorbate 80, or to mushroom products
  • Any comorbid condition or unresolved toxicity that would preclude administration of docetaxel
  • Medical contraindication to any docetaxel pre-medications
  • History of > grade 2 neurotoxicity or any toxicity from any cause that has not resolved to < grade 1
  • Brain or other CNS metastasis
  • The need for chronic daily immunosuppressive therapy, including concurrent use of prednisone
  • Evidence of active second malignancy, except non-melanoma skin cancer
  • Infection requiring intravenous antibiotic therapy or other severe infection within 14 days preceding first dose of study drug
  • Inability to swallow oral medication or maintain a fast, as required 2 hours before and 1 hour after PSK administration
  • Uncontrolled pain at baseline, impending complication from bone metastasis and/or presence of urinary obstruction
  • Other medical or psychiatric condition that may increase the risk associated with trial participation or any other condition in the judgment of the investigator that may interfere with the interpretation of trial results or would make the patient inappropriate for enrollment in this trial
Male
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT01685489
1U19AT006028-01A1
Yes
Bastyr University
Bastyr University
  • University of Washington
  • Fred Hutchinson Cancer Research Center
Study Director: Celestia Higano, MD Seattle Cancer Care Alliance - University of Washington
Study Director: Cynthia A Wenner, Ph.D Bastyr University
Principal Investigator: Leanna J Standish, PhD, ND, LAc Bastyr University
Principal Investigator: Mary (Nora) L Disis, MD University of Washington
Bastyr University
October 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP