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A Phase II Study of SB939 in Patients With Recurrent or Metastatic Castration Resistant Prostate Cancer

Phase 2
18 Years
Open (Enrolling)
Prostate Cancer

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Trial Information

A Phase II Study of SB939 in Patients With Recurrent or Metastatic Castration Resistant Prostate Cancer



- 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.


- 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.

Inclusion Criteria


- Histologically confirmed adenocarcinoma of the prostate

- Presence of clinically and/or radiologically documented disease (target or

- Metastatic or locally recurrent disease for which no curative therapy exists AND for
which systemic chemotherapy is indicated due to progression, meeting the following

- 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


- 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


- 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

- 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

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

PSA response

Outcome Description:

Each patient will have PSA response calculated. Required at the end of every cycle.

Outcome Time Frame:

each cycle

Safety Issue:


Principal Investigator

Kim N. Chi, MD

Investigator Role:

Study Chair

Investigator Affiliation:

British Columbia Cancer Agency


Canada: Health Canada

Study ID:




Start Date:

February 2010

Completion Date:

November 2012

Related Keywords:

  • Prostate Cancer
  • hormone-resistant prostate cancer
  • recurrent prostate cancer
  • stage IV prostate cancer
  • stage III prostate cancer
  • adenocarcinoma of the prostate
  • Prostatic Neoplasms