SB939 in Treating Patients With Recurrent or Metastatic Prostate Cancer

Prostate Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01075308
• Other study ID #: I195
• Secondary ID: CAN-NCIC-IND195C
• Status: Completed
• Phase: Phase 2
• Start date: June 28, 2010
• Est. completion date: February 13, 2015

Study information

• Verified date: April 2020
• Source: Canadian Cancer Trials Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 32
• Est. completion date: February 13, 2015
• Est. primary completion date: January 5, 2015
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years to 120 Years

Eligibility

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

Related Conditions & MeSH terms

• Prostate Cancer
• Prostatic Neoplasms

Intervention

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).

Locations

Country	Name	City	State
Canada	Tom Baker Cancer Centre	Calgary	Alberta
Canada	Cross Cancer Institute	Edmonton	Alberta
Canada	QEII Health Sciences Center	Halifax	Nova Scotia
Canada	BCCA - Cancer Centre for the Southern Interior	Kelowna	British Columbia
Canada	London Regional Cancer Program	London	Ontario
Canada	Univ. Health Network-Princess Margaret Hospital	Toronto	Ontario
Canada	BCCA - Vancouver Cancer Centre	Vancouver	British Columbia

Sponsors (2)

Lead Sponsor	Collaborator
NCIC Clinical Trials Group	S*BIO

Country where clinical trial is conducted

Canada, 

References & Publications (3)

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;

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 Conferenc

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 pros — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	PSA response	Each patient will have PSA response calculated. Required at the end of every cycle.	each cycle
Primary	Progression-free survival	Used as an indicator of efficacy, patients with PSA response will have length of progression free survival calculated.	end of study
Secondary	Objective response rate	Patients with measurable disease will have objective response evaluated.	every other cycle
Secondary	Duration of response	Patients with objective response will have duration of response calculated as will be followed until progression/relapse	every other cycle
Secondary	Safety	Toxicity and tolerability will be evaluated	each cycle
Secondary	Change in circulating tumor cells during study compared to baseline	Patients will have on study samples compared to baseline to look for chance in number of CTC.	each cycle
Secondary	Comparison of TMPRSS2-ERG fusion and PTEN deletion in circulating tumor cells	samples will be taken and analyzed each cycle with a comparison made at end of study.	each cycle
Secondary	Comparison of two systems for counting circulating tumor cells	Two different systems will be used to count CTC. Results will be compared at the end of the study for accuracy.	end of study