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

Information source: Bastyr University
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Prostatic Neoplasms

Intervention: Docetaxel, PSK® (Drug); Docetaxel, Placebo (Drug)

Phase: Phase 1

Status: Suspended

Sponsored by: Bastyr University

Official(s) and/or principal investigator(s):
Celestia Higano, MD, Study Director, Affiliation: Seattle Cancer Care Alliance - University of Washington
Cynthia A Wenner, Ph.D, Study Director, Affiliation: Bastyr University
Leanna J Standish, PhD, ND, LAc, Principal Investigator, Affiliation: Bastyr University
Mary (Nora) L Disis, MD, Principal Investigator, Affiliation: University of Washington


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.

Clinical Details

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

Study design: Allocation: Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Primary outcome:

Determine tolerability dose of PSK alone and in combination with docetaxel

Determine maximum tolerated dose and recommended phase 2 dose of PSK in combination with docetaxel

Secondary outcome:

Pharmacokinetics of docetaxel when combined with oral PSK

Pharmacokinetics of oral PSK dosing and in combination with docetaxel

Immunological laboratory analysis

Clinical tumor markers

Prostatic acid phosphatase


Minimum age: 18 Years. Maximum age: N/A. Gender(s): Male.


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


- 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


- 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


- 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

Locations and Contacts

Seattle Cancer Care Alliance, Seattle, Washington 98109, United States
Additional Information

General information of Bastyr University

Related publications:

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Starting date: May 2013
Last updated: April 16, 2015

Page last updated: August 23, 2015

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