SB939 in Treating Patients With Recurrent or Metastatic Prostate Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
NCIC Clinical Trials Group
ClinicalTrials.gov Identifier:
NCT01075308
First received: February 24, 2010
Last updated: February 7, 2014
Last verified: February 2014
  Purpose

RATIONALE: SB939 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

PURPOSE: This phase II trial is studying how well SB939 works in treating patients with recurrent or metastatic prostate cancer.


Condition Intervention Phase
Prostate Cancer
Drug: HDAC inhibitor SB939
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study of SB939 in Patients With Recurrent or Metastatic Castration Resistant Prostate Cancer

Resource links provided by NLM:


Further study details as provided by NCIC Clinical Trials Group:

Primary Outcome Measures:
  • PSA response [ Time Frame: each cycle ] [ Designated as safety issue: No ]
    Each patient will have PSA response calculated. Required at the end of every cycle.

  • Progression-free survival [ Time Frame: end of study ] [ Designated as safety issue: No ]
    Used as an indicator of efficacy, patients with PSA response will have length of progression free survival calculated.


Secondary Outcome Measures:
  • Objective response rate [ Time Frame: every other cycle ] [ Designated as safety issue: No ]
    Patients with measurable disease will have objective response evaluated.

  • Duration of response [ Time Frame: every other cycle ] [ Designated as safety issue: No ]
    Patients with objective response will have duration of response calculated as will be followed until progression/relapse

  • Safety [ Time Frame: each cycle ] [ Designated as safety issue: Yes ]
    Toxicity and tolerability will be evaluated

  • Change in circulating tumor cells during study compared to baseline [ Time Frame: each cycle ] [ Designated as safety issue: No ]
    Patients will have on study samples compared to baseline to look for chance in number of CTC.

  • Comparison of TMPRSS2-ERG fusion and PTEN deletion in circulating tumor cells [ Time Frame: each cycle ] [ Designated as safety issue: No ]
    samples will be taken and analyzed each cycle with a comparison made at end of study.

  • Comparison of two systems for counting circulating tumor cells [ Time Frame: end of study ] [ Designated as safety issue: No ]
    Two different systems will be used to count CTC. Results will be compared at the end of the study for accuracy.


Enrollment: 32
Study Start Date: February 2010
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: March 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: SB939
SB939 given orally every other day 3 times a week (i.e. Monday /Wednesday /Friday, or Tuesday /Thursday / Saturday) for 3 consecutive weeks followed by one week off-dosing. A treatment cycle is 4 weeks (28 days).
Drug: HDAC inhibitor SB939
SB939 given orally every other day 3 times a week (i.e. Monday /Wednesday /Friday, or Tuesday /Thursday / Saturday) for 3 consecutive weeks followed by one week off-dosing. A treatment cycle is 4 weeks (28 days).

Detailed Description:

OBJECTIVES:

Primary

  • To determine the efficacy, as measured by PSA response and progression-free survival, of HDAC inhibitor SB939 in patients with recurrent or metastatic castration-resistant prostate cancer.

Secondary

  • To determine the objective response and response duration in patients with measurable disease at baseline.
  • To determine the tolerability and toxicity of this drug in these patients.
  • To determine the number of circulating tumor cells at baseline and after 6 weeks (and 12 weeks if patient is still on study treatment).
  • To explore potential molecular factors predictive of response by assessment of archival prostate tumor tissue.
  • To explore ERG and PTEN expression on circulating tumor cells as a potential prognostic and predictive marker for response to this drug.
  • To determine time to PSA and time to objective progression in these patients.

OUTLINE: This is a multicenter study.

Patients receive oral HDAC Inhibitor SB939 once daily on days 1, 3, 5, 8, 10, 12, 15, 17, and 19. Treatment repeats every 4 weeks for up to 12 courses in the absence of disease progression or unacceptable toxicity.

Blood samples are collected periodically for correlative studies. Blood samples and Archival tumor tissue are analyzed for TMPRSS2-ERG fusion and PTEN deletion status by FISH; TMPRSS2-ERG fusion by RT-PCR; and for the number of circulating tumor cells.

After completion of study therapy, patients are followed up at 4 weeks and then every 3 months thereafter.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically confirmed adenocarcinoma of the prostate
  • Presence of clinically and/or radiologically documented disease (target or non-target)
  • Metastatic or locally recurrent disease for which no curative therapy exists AND for which systemic chemotherapy is indicated due to progression, meeting the following criteria:

    • At least two rises in PSA over a reference value OR the development of new metastatic lesions with a stable or rising PSA

      • First rising PSA must be taken at least 1 week after the reference value
      • Third or subsequent PSA must show further increase confirming progression within 2 weeks prior to study enrollment
      • PSA progression must be documented after discontinuation of peripheral antiandrogens (4 weeks for flutamide and 6 weeks for bicalutamide/nilutamide) for patients with documented evidence of progression while receiving peripheral antiandrogens
  • Medically or surgically castrated by androgen ablation

    • Castrate level of testosterone (< 1.7 nmol/L) must be present for patients undergoing medical androgen ablation
  • Received prior hormone therapy

    • Must have hormone-refractory disease
    • Therapy with luteinizing hormone-releasing hormone (LHRH) agonist must continue for patients already receiving this treatment at the time of enrollment
    • Patients who discontinued LHRH agonist must restart therapy (if not surgically castrated) and the castrate level of testosterone must be present
  • PSA ≥ 5 ng/mL
  • Primary or metastatic tumor tissue available
  • No documented CNS metastases

PATIENT CHARACTERISTICS:

  • ECOG performance status 0-1
  • Life expectancy ≥ 12 weeks
  • Absolute granulocyte count ≥ 1.5 x 10^9/L
  • Platelet count ≥ 100 x 10^9/L
  • AST and ALT ≤ 2.5 times upper limit of normal (ULN)
  • Bilirubin normal
  • Serum creatinine normal
  • Potassium normal
  • Calcium normal
  • Fertile patients must use effective contraception
  • QTc ≤ 450 msec
  • LVEF ≥ 50% by Echo or MUGA scan
  • Troponin I or T ≤ ULN
  • Able to take oral medication
  • No preexisting uncontrolled cardiac condition
  • No prior myocardial infarction
  • No history of other malignancies, except adequately treated nonmelanoma skin cancer or other solid tumors curatively treated with no evidence of disease for ≥ 5 years
  • No gastrointestinal abnormalities (e.g., bowel obstruction or previous gastric resection) that would lead to inadequate absorption of HDAC Inhibitor SB939
  • No known HIV positivity or hepatitis B or C infections
  • No chronic medical condition or comorbidity that may increase the risks associated with study participation/study drug administration or may interfere with the interpretation of study results, including any of the following:

    • Pulmonary disease
    • Active infection
    • Psychiatric condition
    • Laboratory abnormality

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • At least 4 weeks since prior antiandrogens (6 weeks for bicalutamide)
  • At least 4 weeks since prior external-beam radiotherapy

    • Exceptions may be made for low-dose, non-myelosuppressive radiotherapy
  • At least 28 days since other prior investigational therapy or anticancer therapy
  • At least 14 days since prior major surgery and wound healing has occurred
  • No more than 1 prior chemotherapy regimen allowed and recovered from significant toxicity
  • No prior strontium
  • No prior HDAC inhibitors
  • No current agents (dysrhythmic drugs) with a known risk of Torsades de Pointes
  • No other concurrent cytotoxic therapy or radiotherapy
  • No other concurrent investigational therapy
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01075308

Locations
Canada, Alberta
Tom Baker Cancer Centre
Calgary, Alberta, Canada, T2N 4N2
Cross Cancer Institute
Edmonton, Alberta, Canada, T6G 1Z2
Canada, British Columbia
BCCA - Cancer Centre for the Southern Interior
Kelowna, British Columbia, Canada, V1Y 5L3
BCCA - Vancouver Cancer Centre
Vancouver, British Columbia, Canada, V5Z 4E6
Canada, Nova Scotia
QEII Health Sciences Center
Halifax, Nova Scotia, Canada, B3H 1V7
Canada, Ontario
London Regional Cancer Program
London, Ontario, Canada, N6A 4L6
Univ. Health Network-Princess Margaret Hospital
Toronto, Ontario, Canada, M5G 2M9
Sponsors and Collaborators
NCIC Clinical Trials Group
Investigators
Study Chair: Kim N. Chi, MD British Columbia Cancer Agency
Study Chair: Bernhard Eigl, MD, FRCPC Tom Baker Cancer Centre - Calgary
  More Information

Additional Information:
No publications provided

Responsible Party: NCIC Clinical Trials Group
ClinicalTrials.gov Identifier: NCT01075308     History of Changes
Other Study ID Numbers: I195, CAN-NCIC-IND195, CDR0000666241
Study First Received: February 24, 2010
Last Updated: February 7, 2014
Health Authority: Canada: Health Canada

Keywords provided by NCIC Clinical Trials Group:
hormone-resistant prostate cancer
recurrent prostate cancer
stage IV prostate cancer
stage III prostate cancer
adenocarcinoma of the prostate

Additional relevant MeSH terms:
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases
Histone Deacetylase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

ClinicalTrials.gov processed this record on October 16, 2014