SB939 in Treating Patients With Recurrent or Metastatic Prostate Cancer

Sponsor

NCIC Clinical Trials Group (Other)

Overall Status

Completed

CT.gov ID

NCT01075308

Collaborator

S*BIO (Industry)

Enrollment

Locations

Arm

60.1

Actual Duration (Months)

4.6

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Prostate Cancer	Drug: HDAC inhibitor SB939	Phase 2

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

32 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Feb 10, 2010

Actual Primary Completion Date :

Jan 5, 2015

Actual Study Completion Date :

Feb 13, 2015

Arms and Interventions

Arm	Intervention/Treatment
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).

Arm

Intervention/Treatment

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

Outcome Measures

Primary Outcome Measures

PSA response [each cycle]
Each patient will have PSA response calculated. Required at the end of every cycle.
Progression-free survival [end of study]
Used as an indicator of efficacy, patients with PSA response will have length of progression free survival calculated.

Secondary Outcome Measures

Objective response rate [every other cycle]
Patients with measurable disease will have objective response evaluated.
Duration of response [every other cycle]
Patients with objective response will have duration of response calculated as will be followed until progression/relapse
Safety [each cycle]
Toxicity and tolerability will be evaluated
Change in circulating tumor cells during study compared to baseline [each cycle]
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 [each cycle]
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 [end of study]
Two different systems will be used to count CTC. Results will be compared at the end of the study for accuracy.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 120 Years

Sexes Eligible for Study:

Male

Accepts Healthy Volunteers:

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

Locations

	Site	City	State	Country	Postal Code
1	Tom Baker Cancer Centre	Calgary	Alberta	Canada	T2N 4N2
2	Cross Cancer Institute	Edmonton	Alberta	Canada	T6G 1Z2
3	BCCA - Cancer Centre for the Southern Interior	Kelowna	British Columbia	Canada	V1Y 5L3
4	BCCA - Vancouver Cancer Centre	Vancouver	British Columbia	Canada	V5Z 4E6
5	QEII Health Sciences Center	Halifax	Nova Scotia	Canada	B3H 1V7
6	London Regional Cancer Program	London	Ontario	Canada	N6A 4L6
7	Univ. Health Network-Princess Margaret Hospital	Toronto	Ontario	Canada	M5G 2M9