Know Cancer

forgot password

A Phase I Clinical and Pharmacokinetic Study of SB939 in Patients With Advanced Cancer

Phase 1
18 Years
Not Enrolling
Unspecified Adult Solid Tumor, Protocol Specific

Thank you

Trial Information

A Phase I Clinical and Pharmacokinetic Study of SB939 in Patients With Advanced Cancer



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


- To determine the toxic effects of SB939 and its association with dose and

- 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

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.

Inclusion Criteria


Inclusion criteria:

- Histologically or cytologically confirmed locally advanced or metastatic solid tumor

- Refractory to standard therapy or for which conventional therapy is not reliably

Exclusion criteria:

- Patients with documented CNS metastases


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

- Presence of any significant psychiatric disorder that would hamper the patient's

- 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


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

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Recommended phase II dose

Outcome Description:

Assess for safety, tolerability, toxicity profile and dose limiting toxicities

Outcome Time Frame:

Each dose level

Safety Issue:


Principal Investigator

Lillian L. Siu, MD, FRCPC

Investigator Role:

Study Chair

Investigator Affiliation:

Princess Margaret Hospital, Canada


Canada: Health Canada

Study ID:




Start Date:

June 2007

Completion Date:

June 2011

Related Keywords:

  • Unspecified Adult Solid Tumor, Protocol Specific
  • unspecified adult solid tumor, protocol specific
  • Neoplasms