SB939 in Treating Patients With Locally Advanced or Metastatic Solid Tumors

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
NCIC Clinical Trials Group
ClinicalTrials.gov Identifier:
NCT00504296
First received: July 17, 2007
Last updated: May 31, 2012
Last verified: May 2012
  Purpose

RATIONALE: SB939 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

PURPOSE: This phase I trial is studying the side effects and best dose of SB939 in treating patients with locally advanced or metastatic solid tumors.


Condition Intervention Phase
Unspecified Adult Solid Tumor, Protocol Specific
Drug: HDAC inhibitor SB939
Other: immunoenzyme technique
Other: immunohistochemistry staining method
Other: immunologic technique
Other: laboratory biomarker analysis
Other: liquid chromatography
Other: mass spectrometry
Other: pharmacological study
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Clinical and Pharmacokinetic Study of SB939 in Patients With Advanced Cancer

Resource links provided by NLM:


Further study details as provided by NCIC Clinical Trials Group:

Primary Outcome Measures:
  • Recommended phase II dose [ Time Frame: Each dose level ] [ Designated as safety issue: Yes ]
    Assess for safety, tolerability, toxicity profile and dose limiting toxicities


Secondary Outcome Measures:
  • Safety [ Time Frame: Each dose level ] [ Designated as safety issue: Yes ]
    Safety, tolerability, toxicity profile, dose limiting toxicities of SB939.

  • Pharmacokinetic profile [ Time Frame: Cycle 1 day 1 and 15 ] [ Designated as safety issue: No ]
    Samples collected over multiple timepoints

  • SB939 effects on histone H3 acetylation [ Time Frame: Cycle 1 days 1 and 15 ] [ Designated as safety issue: No ]
    Levels of AcH3 will be determined using wetern Blot, immunohistochemistry or Elisa method.


Enrollment: 39
Study Start Date: June 2007
Study Completion Date: June 2011
Primary Completion Date: March 2010 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: HDAC inhibitor SB939
    SB939 will be administered initially for 3 consecutive days every other week at the first dose level and then for 5 consecutive days every other week at escalating doses.
    Other: immunoenzyme technique Other: immunohistochemistry staining method Other: immunologic technique Other: laboratory biomarker analysis Other: liquid chromatography Other: mass spectrometry Other: pharmacological study
Detailed Description:

OBJECTIVES:

Primary

  • To determine the recommended phase II dose of oral SB939 in patients with solid tumors.

Secondary

  • To determine the toxic effects of SB939 and its association with dose and pharmacokinetics.
  • To assess the pharmacokinetic profile of SB939.
  • To assess preliminary evidence of antitumor effects of SB939 in patients with measurable disease as documented by objective response.
  • To establish proof-of-principle for SB939 effects on histone acetylation by evaluation of histone acetylation and other biomarkers in peripheral blood mononuclear cells (PBMCs) at all dose levels.

OUTLINE: Patients receive oral SB939 once daily on days 1-5 and 15-19. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Patients undergo blood sample collection periodically during course 1 for pharmacokinetic and pharmacodynamic studies. Samples are analyzed for levels of SB939 via LC-MS/MS method and levels of acetylated histone 3 (AcH3), target effect, downstream consequences, and tumor response via western blot, immunohistochemistry, or ELISA methods.

After completion of study treatment, patients are followed at 4 weeks and then every 3 months thereafter.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

Inclusion criteria:

  • Histologically or cytologically confirmed locally advanced or metastatic solid tumor

    • Refractory to standard therapy or for which conventional therapy is not reliably effective

Exclusion criteria:

  • Patients with documented CNS metastases

PATIENT CHARACTERISTICS:

Inclusion criteria:

  • ECOG performance status of 0, 1, or 2
  • Must have a life expectancy of ≥ 12 weeks
  • Granulocytes (AGC) ≥ 1.5 x 10^9/L
  • Platelets ≥ 100 x 10^9/L
  • Bilirubin ≤ upper limit of normal (ULN)
  • AST and ALT ≤ 2.5 x ULN (< 5 x ULN if liver metastases are present)
  • Serum creatinine ≤ 1.2 x ULN OR creatinine clearance ≥ 60 mL/min
  • QTc ≤ 450 msec
  • LVEF ≥ 50% by ECHO or MUGA
  • Troponin I or T ≤ ULN
  • Must be within 1½ hour's driving distance

Exclusion criteria:

  • Pathologic cardiac arrhythmia requiring active treatment

    • Patients with a history of arrhythmia must be > 12 months since last treatment with no recurrence of arrhythmia in the interval
  • Inability to take oral medication

    • Patients must be able to swallow SB939 capsules and have no gastrointestinal abnormalities (e.g., bowel obstruction or previous gastric resection) which would lead to inadequate absorption of SB939
  • Pregnant or lactating women

    • Urine or serum B-HCG must be negative
  • Women or men of child-bearing potential unless using effective contraception
  • Presence of any clinically significant co-morbidities (i.e., pulmonary disease, active CNS disease, or active infection)
  • Presence of any other significant CNS disorder that would hamper the patient's compliance
  • Presence of any significant psychiatric disorder that would hamper the patient's compliance
  • Other acute or chronic medical condition, psychiatric condition, or laboratory abnormality that may increase the risks associated with study participation/study drug administration or may interfere with the interpretation of study results
  • Pre-existing peripheral neuropathy ≥ grade 2
  • Known HIV or hepatitis B or C infection

PRIOR CONCURRENT THERAPY:

Inclusion criteria:

  • Previous anticancer treatment must be discontinued at least 28 days prior to the first dose of study treatment (42 days [6 weeks] for nitrosoureas or mitomycin C)
  • At least 28 days since prior radiation therapy restricted to ≤ 30% of the bone marrow and recovered from toxic effects

    • Exceptions may be made for low-dose nonmyelosuppressive radiotherapy
  • Must be ≥ 14 days since any major surgery
  • Pre-existing bisphosphonate or luteinizing hormone-releasing hormone (LHRH) analog therapy (for men with hormone refractory prostate cancer) may be continued during study participation

Exclusion criteria:

  • Previous treatment with a histone deacetylase (HDAC) inhibitor
  • Treatment with another investigational therapy within 28 days prior to study entry
  • Other concurrent anticancer treatment or investigational therapy
  • Concurrent agents with a known risk of Torsade de Pointes
  • Concurrent G-CSF, GM-CSF, or other hematopoietic growth factors may not be used as a substitute for a scheduled dose reduction (may be used in the management of acute toxicity)
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00504296

Locations
Canada, Ontario
Juravinski Cancer Centre at Hamilton Health Sciences
Hamilton, Ontario, Canada, L8V 5C2
Univ. Health Network-Princess Margaret Hospital
Toronto, Ontario, Canada, M5G 2M9
Sponsors and Collaborators
NCIC Clinical Trials Group
Investigators
Study Chair: Lillian L. Siu, MD, FRCPC Princess Margaret Hospital, Canada
  More Information

Additional Information:
Publications:
Razak ARA, Hotte SJ, Siu LL, Chen EX, Hirte HW, Powers J, Walsh W, Stayner LA, Laughlin A, Novotny-Diermayr V, Zhu J, Eisenhauer EA Phase I clinical, pharmacokinetic and pharmacodynamic study of SB939, an oral histone deacetylase (HDAC) inhibitor, in patients with advanced solid tumours British Journal of Cancer:104(5):756 -762,2011

Responsible Party: NCIC Clinical Trials Group
ClinicalTrials.gov Identifier: NCT00504296     History of Changes
Other Study ID Numbers: I188, CAN-NCIC-IND188, S*BIO-SB939-2007-002, CDR0000558934
Study First Received: July 17, 2007
Last Updated: May 31, 2012
Health Authority: Canada: Health Canada

Keywords provided by NCIC Clinical Trials Group:
unspecified adult solid tumor, protocol specific

Additional relevant MeSH terms:
Histone Deacetylase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 15, 2014