SB939 in Treating Patients With Recurrent or Metastatic Prostate Cancer

NCIC Clinical Trials Group

Status and phase: Completed; Phase 2

Conditions: Prostate Cancer

Treatments: Drug: HDAC inhibitor SB939

Study type: Interventional

Funder types: NETWORK; Industry

Identifiers

NCT01075308

CDR0000666241 (Other Identifier)

I195

CAN-NCIC-IND195 (Registry Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 32 patients

Sex: Male

Ages: 18 to 120 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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32 participants in 1 patient group

SB939

Experimental group

Description:

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).

Treatment:

Drug: HDAC inhibitor SB939