Clinical trial NCT01075308: SB939 in Treating Patients With Recurrent or Metastatic Prostate Cancer
Official title: A Phase II Study of SB939 in Patients With Recurrent or Metastatic Castration Resistant Prostate Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Prostate Cancer
Keywords: hormone-resistant prostate cancer
recurrent prostate cancer
stage IV prostate cancer
stage III prostate cancer
adenocarcinoma of the prostate
Lead sponsor: Canadian Cancer Trials Group
Sponsor class: NETWORK
Collaborators: name: S*BIO
First posted: 2010-02-25
Enrollment: 32
Sex: MALE
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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 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

Primary outcomes:
measure: PSA response
timeFrame: each cycle
measure: Progression-free survival
timeFrame: end of study
Secondary outcomes:
measure: Objective response rate
timeFrame: every other cycle
measure: Duration of response
timeFrame: every other cycle
measure: Safety
timeFrame: each cycle
measure: Change in circulating tumor cells during study compared to baseline
timeFrame: each cycle
measure: Comparison of TMPRSS2-ERG fusion and PTEN deletion in circulating tumor cells
timeFrame: each cycle
measure: Comparison of two systems for counting circulating tumor cells
timeFrame: end of study
Other outcomes:
Locations:
city: Calgary
country: Canada
facility: Tom Baker Cancer Centre
state: Alberta
city: Edmonton
country: Canada
facility: Cross Cancer Institute
state: Alberta
city: Kelowna
country: Canada
facility: BCCA - Cancer Centre for the Southern Interior
state: British Columbia
city: Vancouver
country: Canada
facility: BCCA - Vancouver Cancer Centre
state: British Columbia
city: Halifax
country: Canada
facility: QEII Health Sciences Center
state: Nova Scotia
city: London
country: Canada
facility: London Regional Cancer Program
state: Ontario
city: Toronto
country: Canada
facility: Univ. Health Network-Princess Margaret Hospital
state: Ontario
Study officials:
affiliation: British Columbia Cancer Agency
name: Kim N. Chi, MD
role: STUDY_CHAIR
affiliation: Tom Baker Cancer Centre - Calgary
name: Bernhard Eigl, MD, FRCPC
role: STUDY_CHAIR
References:
citation: Eigl BJ, North S, Murray N, Heng DYC, Winquist E, Powers J, Walsh WR, Eisenhauer E, Squire J, Cox M, Chi KN. A Phase II Study of SB939 in Patients with Recurrent or Metastatic Castration Resistant Prostate Cancer (CRPC). AACR Mol Cancer Tehr 10[11 Suppl; abstr A211]. 2011
citation: Eigl BJ, North S, Murray N, Heng DYC, Winquist E, Powers J, Walsh WR, Eisenhauer E, Squire J, Cox M, Chi KN. A Phase II Study of SB939 in Patients with Recurrent or Metastatic Castration Resistant Prostate Cancer (CRPC). Canadian Cacner Research Conference. 2011.
citation: Eigl BJ, North S, Winquist E, Finch D, Wood L, Sridhar SS, Powers J, Good J, Sharma M, Squire JA, Bazov J, Jamaspishvili T, Cox ME, Bradbury PA, Eisenhauer EA, Chi KN. A phase II study of the HDAC inhibitor SB939 in patients with castration resistant prostate cancer: NCIC clinical trials group study IND195. Invest New Drugs. 2015 Aug;33(4):969-76. doi: 10.1007/s10637-015-0252-4. Epub 2015 May 19.