SB939 in Treating Patients With Locally Advanced or Metastatic Solid Tumors

NCIC Clinical Trials Group

Status and phase

Completed

Phase 1

Conditions

Unspecified Adult Solid Tumor, Protocol Specific

Treatments

Drug: HDAC inhibitor SB939

Other: immunohistochemistry staining method

Other: laboratory biomarker analysis

Other: mass spectrometry

Other: immunoenzyme technique

Other: immunologic technique

Other: liquid chromatography

Other: pharmacological study

Study type

Interventional

Funder types

NETWORK

Industry

Identifiers

NCT00504296

I188

CAN-NCIC-IND188 (Registry Identifier)

S*BIO-SB939-2007-002 (Other Identifier)

CDR0000558934 (Other 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 I trial is studying the side effects and best dose of SB939 in treating patients with locally advanced or metastatic solid tumors.

Full 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.

Enrollment

39 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion 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)