SB939 in Treating Patients With Locally Advanced or Metastatic Solid Tumors
Study Details
Study Description
Brief Summary
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 or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: SB939
|
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
|
Outcome Measures
Primary Outcome Measures
- Recommended phase II dose [Each dose level]
Assess for safety, tolerability, toxicity profile and dose limiting toxicities
Secondary Outcome Measures
- Safety [Each dose level]
Safety, tolerability, toxicity profile, dose limiting toxicities of SB939.
- Pharmacokinetic profile [Cycle 1 day 1 and 15]
Samples collected over multiple timepoints
- SB939 effects on histone H3 acetylation [Cycle 1 days 1 and 15]
Levels of AcH3 will be determined using wetern Blot, immunohistochemistry or Elisa method.
Eligibility Criteria
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
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Urine or serum B-HCG must be negative
-
Women or men of child-bearing potential unless using effective contraception
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Presence of any clinically significant co-morbidities (i.e., pulmonary disease, active CNS disease, or active infection)
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Presence of any other significant CNS disorder that would hamper the patient's compliance
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Presence of any significant psychiatric disorder that would hamper the patient's compliance
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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
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Juravinski Cancer Centre at Hamilton Health Sciences | Hamilton | Ontario | Canada | L8V 5C2 |
| 2 | Univ. Health Network-Princess Margaret Hospital | Toronto | Ontario | Canada | M5G 2M9 |
Sponsors and Collaborators
- NCIC Clinical Trials Group
- S*BIO
Investigators
- Study Chair: Lillian L. Siu, MD, FRCPC, Princess Margaret Hospital, Canada
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- I188
- CAN-NCIC-IND188
- S*BIO-SB939-2007-002
- CDR0000558934