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

October 23, 2015 updated by: Bastyr University
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.

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

Study Type

Interventional

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Washington
      • Seattle, Washington, United States, 98109
        • Seattle Cancer Care Alliance

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Male

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: DOUBLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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.
Drug: Docetaxel, PSK®
Other Names:
  • Krestin
  • Polysaccharide-K
  • Polysaccharide-Kureha
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.
Drug: Docetaxel, Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Determine tolerability dose of PSK alone and in combination with docetaxel
Time Frame: 42 days
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.
42 days
Determine maximum tolerated dose and recommended phase 2 dose of PSK in combination with docetaxel
Time Frame: 106 days
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.
106 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Pharmacokinetics of docetaxel when combined with oral PSK
Time Frame: 106 days
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.
106 days
Pharmacokinetics of oral PSK dosing and in combination with docetaxel
Time Frame: 106 days
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.
106 days
Immunological laboratory analysis
Time Frame: 106 days
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.
106 days
Clinical tumor markers
Time Frame: 106 days
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.
106 days
Prostatic acid phosphatase
Time Frame: 106
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.
106

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Bastyr University

Collaborators

University of Washington
Fred Hutchinson Cancer Center

Investigators

  • 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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2013

Study Registration Dates

First Submitted

September 6, 2012

First Submitted That Met QC Criteria

September 13, 2012

First Posted (ESTIMATE)

September 14, 2012

Study Record Updates

Last Update Posted (ESTIMATE)

October 27, 2015

Last Update Submitted That Met QC Criteria

October 23, 2015

Last Verified

October 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 1U19AT006028-01A1 (NIH)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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