SB939 in Treating Patients With Locally Advanced or Metastatic Solid Tumors

NCT ID: NCT00504296

Last Updated: 2023-08-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 39 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-09-14
• Study Completion Date: 2011-06-21

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.

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.

Conditions

Unspecified Adult Solid Tumor, Protocol Specific

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

SB939

Group Type: EXPERIMENTAL

HDAC inhibitor SB939

Intervention Type: DRUG

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.

immunoenzyme technique

Intervention Type: OTHER

immunohistochemistry staining method

Intervention Type: OTHER

immunologic technique

Intervention Type: OTHER

laboratory biomarker analysis

Intervention Type: OTHER

liquid chromatography

Intervention Type: OTHER

mass spectrometry

Intervention Type: OTHER

pharmacological study

Intervention Type: OTHER

Interventions

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.

Intervention Type: DRUG

immunoenzyme technique

Intervention Type: OTHER

immunohistochemistry staining method

Intervention Type: OTHER

immunologic technique

Intervention Type: OTHER

laboratory biomarker analysis

Intervention Type: OTHER

liquid chromatography

Intervention Type: OTHER

mass spectrometry

Intervention Type: OTHER

pharmacological study

Intervention Type: OTHER

Eligibility 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 effective

• 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

• 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

• Patients with documented CNS metastases

PATIENT CHARACTERISTICS:

• 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:

• 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)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

S*BIO

INDUSTRY

Sponsor Role: collaborator

NCIC Clinical Trials Group

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Lillian L. Siu, MD, FRCPC

Role: STUDY_CHAIR

Princess Margaret Hospital, Canada

Locations

Juravinski Cancer Centre at Hamilton Health Sciences

Hamilton, Ontario, Canada

Univ. Health Network-Princess Margaret Hospital

Toronto, Ontario, Canada

Countries

Canada

References

Razak AR, 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. Br J Cancer. 2011 Mar 1;104(5):756-62. doi: 10.1038/bjc.2011.13. Epub 2011 Feb 1.

Reference Type: RESULT

PMID: 21285985 (View on PubMed)

Other Identifiers

CAN-NCIC-IND188

Identifier Type: REGISTRY

Identifier Source: secondary_id

S*BIO-SB939-2007-002

Identifier Type: OTHER

Identifier Source: secondary_id

CDR0000558934

Identifier Type: OTHER

Identifier Source: secondary_id

I188

Identifier Type: -

Identifier Source: org_study_id