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

NCT01685489 | Withdrawn Phase 1 DMC

• 1 other identifier: 1U19AT006028-01A1
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

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.

Conditions

Prostatic Neoplasms

Keywords

Prostate; Neoplasm; Adenocarcinoma; Cancer; Metastatic; Castrate resistant; Docetaxel; PSK; Krestin; Trametes versicolor; Safety; Maximum tolerated dose; Mushroom; Natural; Immunotherapy

Outcome Measures

Primary Outcomes (2)

• Determine tolerability dose of PSK alone and in combination with docetaxel

  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

  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 Outcomes (5)

• Pharmacokinetics of docetaxel when combined with oral PSK

  106 days

• Pharmacokinetics of oral PSK dosing and in combination with docetaxel

  106 days

• Immunological laboratory analysis

  106 days

• Clinical tumor markers

  106 days

• Prostatic acid phosphatase

  106

Study Arms (2)

Docetaxel, PSK®

EXPERIMENTAL

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®

Docetaxel, Placebo

PLACEBO COMPARATOR

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

Interventions

Docetaxel, PSK® DRUG

Also known as: Polysaccharide-K, Krestin, Polysaccharide-Kureha

Docetaxel, PSK®

Docetaxel, Placebo DRUG

Docetaxel, Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Bastyr University: lead
• University of Washington: collaborator
• Fred Hutchinson Cancer Center: collaborator

Study Sites (1)

Seattle Cancer Care Alliance

Seattle, Washington, 98109, United States

Location

Related Publications (21)

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• Nakazato H, Koike A, Saji S, Ogawa N, Sakamoto J. Efficacy of immunochemotherapy as adjuvant treatment after curative resection of gastric cancer. Study Group of Immunochemotherapy with PSK for Gastric Cancer. Lancet. 1994 May 7;343(8906):1122-6. doi: 10.1016/s0140-6736(94)90233-x.

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Related Links

• General information of Bastyr University

MeSH Terms

Conditions

Prostatic Neoplasms; Neoplasms; Adenocarcinoma; Neoplasm Metastasis

Interventions

Docetaxel; polysaccharide-K

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Study Officials

• Celestia Higano, MD

  Seattle Cancer Care Alliance - University of Washington

  STUDY DIRECTOR

• Cynthia A Wenner, Ph.D

  Bastyr University

  STUDY DIRECTOR

• Leanna J Standish, PhD, ND, LAc

  Bastyr University

  PRINCIPAL INVESTIGATOR

• Mary (Nora) L Disis, MD

  University of Washington

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 6, 2012
• First Posted: September 14, 2012
• Study Start: May 1, 2013
• Last Updated: October 27, 2015

Record last verified: 2015-10

Locations

US (1)