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

Sponsor

Bastyr University (Other)

Overall Status

Withdrawn

CT.gov ID

NCT01685489

Collaborator

University of Washington (Other), Fred Hutchinson Cancer Center (Other)

Enrollment

Location

Arms

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Prostatic Neoplasms	Drug: Docetaxel, PSK® Drug: Docetaxel, Placebo	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

0 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

May 1, 2013

Arms and Interventions

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: Polysaccharide-K Krestin 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

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:

Polysaccharide-K

Krestin

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

Outcome Measures

Primary Outcome Measures

Determine tolerability dose of PSK alone and in combination with docetaxel [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.
Determine maximum tolerated dose and recommended phase 2 dose of PSK in combination with docetaxel [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.

Secondary Outcome Measures

Pharmacokinetics of docetaxel when combined with oral PSK [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.
Pharmacokinetics of oral PSK dosing and in combination with docetaxel [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.
Immunological laboratory analysis [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.
Clinical tumor markers [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.
Prostatic acid phosphatase [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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Male

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Seattle Cancer Care Alliance	Seattle	Washington	United States	98109

Sponsors and Collaborators

Bastyr University
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