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Prostatic NeoplasmsPhase 1NCT01685489

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

A Phase 1 study testing Docetaxel, PSK® in people with Prostatic Neoplasms, run by Bastyr University at 1 site in United States.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older, men only
Conditions the study is for
Prostatic Neoplasms
What is being tested?
Docetaxel, PSK®
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
0 participants
Where
1 siteUnited States
Study dates
May 2013to not given
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Men only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 24Show fewer
  • 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)

Who cannot join

  • 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
Show all 19Show fewer
  • 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

Trial locations and contacts

1 site in 1 country.

United States1 site
  • Seattle Cancer Care Alliance

    Seattle, Washington, 98109

Other trials in United States

About this study

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.

Being tested
Docetaxel, PSK®, Docetaxel, Placebo
Keywords
Prostate, Neoplasm, Adenocarcinoma, Cancer, Metastatic, Castrate resistant, Docetaxel, PSK, Krestin, Trametes versicolor, Safety, Maximum tolerated dose, Mushroom, Natural, Immunotherapy
Medical subject headings
Prostatic Neoplasms, Neoplasms, Adenocarcinoma, Neoplasm Metastasis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Docetaxel, PSK®Drug

    Also called Polysaccharide-K, Krestin, Polysaccharide-Kureha

  • Docetaxel, PlaceboDrug

Study groups in NCT01685489
Study groupRoleWhat they receive
Docetaxel, PSK®ExperimentalA 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.
Receives: Drug: Docetaxel, PSK®
Docetaxel, PlaceboPlacebo comparatorA 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.
Receives: Drug: Docetaxel, Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: 42 days

  2. 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.

    Measured: 106 days

Secondary outcomes (5)
  1. Pharmacokinetics of docetaxel when combined with oral PSK

    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.

    Measured: 106 days

  2. Pharmacokinetics of oral PSK dosing and in combination with docetaxel

    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.

    Measured: 106 days

  3. Immunological laboratory analysis

    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.

    Measured: 106 days

  4. Clinical tumor markers

    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.

    Measured: 106 days

  5. Prostatic acid phosphatase

    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.

    Measured: 106

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted14 Sep 2012 (estimated)
  2. Study startMay 2013

Why it stopped: funding sequestered

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01685489
Sponsor's protocol ID
1U19AT006028-01A1
Status last verified
Oct 2015
First submitted
6 Sep 2012
Last updated
27 Oct 2015
Results posted
No
Data monitoring committee
Yes

Publications

  • Antonarakis ES, Drake CG. Current status of immunological therapies for prostate cancer. Curr Opin Urol. 2010 May;20(3):241-6. doi: 10.1097/MOU.0b013e3283381793.

    PubMed 20179598
  • de Bono JS, Scher HI, Montgomery RB, Parker C, Miller MC, Tissing H, Doyle GV, Terstappen LW, Pienta KJ, Raghavan D. Circulating tumor cells predict survival benefit from treatment in metastatic castration-resistant prostate cancer. Clin Cancer Res. 2008 Oct 1;14(19):6302-9. doi: 10.1158/1078-0432.CCR-08-0872.

    PubMed 18829513
  • Fisher M, Yang LX. Anticancer effects and mechanisms of polysaccharide-K (PSK): implications of cancer immunotherapy. Anticancer Res. 2002 May-Jun;22(3):1737-54.

    PubMed 12168863
  • Fizazi K, Sternberg CN, Fitzpatrick JM, Watson RW, Tabesh M. Role of targeted therapy in the treatment of advanced prostate cancer. BJU Int. 2010 Mar;105(6):748-67. doi: 10.1111/j.1464-410X.2010.09236.x.

    PubMed 20353536
  • Fujita H, Ogawa K, Ikuzawa M, Muto S, Matsuki M, Nakajima S, Shimamura M, Togawa M, Yoshikumi C, Kawai Y. Effect of PSK, a protein-bound polysaccharide from Coriolus versicolor, on drug-metabolizing enzymes in sarcoma-180 bearing and normal mice. Int J Immunopharmacol. 1988;10(4):445-50. doi: 10.1016/0192-0561(88)90132-4.

    PubMed 3139576
  • Hurria A, Fleming MT, Baker SD, Kelly WK, Cutchall K, Panageas K, Caravelli J, Yeung H, Kris MG, Gomez J, Miller VA, D'Andrea G, Scher HI, Norton L, Hudis C. Pharmacokinetics and toxicity of weekly docetaxel in older patients. Clin Cancer Res. 2006 Oct 15;12(20 Pt 1):6100-5. doi: 10.1158/1078-0432.CCR-06-0200.

    PubMed 17062686
  • Iino Y, Yokoe T, Maemura M, Horiguchi J, Takei H, Ohwada S, Morishita Y. Immunochemotherapies versus chemotherapy as adjuvant treatment after curative resection of operable breast cancer. Anticancer Res. 1995 Nov-Dec;15(6B):2907-11.

    PubMed 8669887
  • Ikuzawa M, Matsunaga K, Nishiyama S, Nakajima S, Kobayashi Y, Andoh T, Kobayashi A, Ohhara M, Ohmura Y, Wada T, et al. Fate and distribution of an antitumor protein-bound polysaccharide PSK (Krestin). Int J Immunopharmacol. 1988;10(4):415-23. doi: 10.1016/0192-0561(88)90128-2.

    PubMed 3170055
  • Lu H, Yang Y, Gad E, Inatsuka C, Wenner CA, Disis ML, Standish LJ. TLR2 agonist PSK activates human NK cells and enhances the antitumor effect of HER2-targeted monoclonal antibody therapy. Clin Cancer Res. 2011 Nov 1;17(21):6742-53. doi: 10.1158/1078-0432.CCR-11-1142. Epub 2011 Sep 14.

    PubMed 21918170
  • Makkouk A, Abdelnoor AM. The potential use of Toll-like receptor (TLR) agonists and antagonists as prophylactic and/or therapeutic agents. Immunopharmacol Immunotoxicol. 2009;31(3):331-8. doi: 10.1080/08923970902802926.

    PubMed 19555209
  • Mickey DD, Bencuya PS, Foulkes K. Effects of the immunomodulator PSK on growth of human prostate adenocarcinoma in immunodeficient mice. Int J Immunopharmacol. 1989;11(7):829-38. doi: 10.1016/0192-0561(89)90137-9.

    PubMed 2599718
  • 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.

    PubMed 7910230
  • Oba K, Teramukai S, Kobayashi M, Matsui T, Kodera Y, Sakamoto J. Efficacy of adjuvant immunochemotherapy with polysaccharide K for patients with curative resections of gastric cancer. Cancer Immunol Immunother. 2007 Jun;56(6):905-11. doi: 10.1007/s00262-006-0248-1. Epub 2006 Nov 15.

    PubMed 17106715
  • Odabasi Z, Mattiuzzi G, Estey E, Kantarjian H, Saeki F, Ridge RJ, Ketchum PA, Finkelman MA, Rex JH, Ostrosky-Zeichner L. Beta-D-glucan as a diagnostic adjunct for invasive fungal infections: validation, cutoff development, and performance in patients with acute myelogenous leukemia and myelodysplastic syndrome. Clin Infect Dis. 2004 Jul 15;39(2):199-205. doi: 10.1086/421944. Epub 2004 Jun 28.

    PubMed 15307029
  • Ostrosky-Zeichner L, Alexander BD, Kett DH, Vazquez J, Pappas PG, Saeki F, Ketchum PA, Wingard J, Schiff R, Tamura H, Finkelman MA, Rex JH. Multicenter clinical evaluation of the (1-->3) beta-D-glucan assay as an aid to diagnosis of fungal infections in humans. Clin Infect Dis. 2005 Sep 1;41(5):654-9. doi: 10.1086/432470. Epub 2005 Jul 21.

    PubMed 16080087

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Docetaxel, PSK® in people with Prostatic Neoplasms, run by Bastyr University at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 24 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 27 Oct 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Determine tolerability dose of PSK alone and in combination with docetaxel (time frame: 42 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01685489, which also lists 21 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Oct 2015.

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