Unspecified Adult Solid Tumor, Protocol SpecificPhase 1NCT00504296
SB939 in Treating Patients With Locally Advanced or Metastatic Solid Tumors
A Phase 1 study testing HDAC inhibitor SB939, immunoenzyme technique and immunohistochemistry staining method in people with Unspecified Adult Solid Tumor, Protocol Specific, run by NCIC Clinical Trials Group at 2 sites in Canada.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Unspecified Adult Solid Tumor, Protocol Specific
- What is being tested?
- HDAC inhibitor SB939, immunoenzyme technique and immunohistochemistry staining method
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 39 participants
- Where
- 2 sitesCanada
- Study dates
- 14 Sep 2007to 21 Jun 2011
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 18Show fewer
- 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
Who cannot join
- 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
Show all 21Show fewer
- 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)
Trial locations and contacts
2 sites in 1 country.
Canada2 sites
Juravinski Cancer Centre at Hamilton Health Sciences
Hamilton, Ontario, L8V 5C2
Univ. Health Network-Princess Margaret Hospital
Toronto, Ontario, M5G 2M9
About this study
Official title: A Phase I Clinical and Pharmacokinetic Study of SB939 in Patients With Advanced Cancer
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.
Read the 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.
- Being tested
- HDAC inhibitor SB939, immunoenzyme technique, immunohistochemistry staining method, immunologic technique, laboratory biomarker analysis
- Keywords
- unspecified adult solid tumor, protocol specific
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
HDAC inhibitor SB939Drug
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 techniqueOther
immunologic techniqueOther
laboratory biomarker analysisOther
liquid chromatographyOther
mass spectrometryOther
| Study group | Role | What they receive |
|---|---|---|
| SB939 | Experimental | Not described Receives: 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 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Recommended phase II dose
Assess for safety, tolerability, toxicity profile and dose limiting toxicities
Measured: Each dose level
Secondary outcomes (3)
Safety
Safety, tolerability, toxicity profile, dose limiting toxicities of SB939.
Measured: Each dose level
Pharmacokinetic profile
Samples collected over multiple timepoints
Measured: Cycle 1 day 1 and 15
SB939 effects on histone H3 acetylation
Levels of AcH3 will be determined using wetern Blot, immunohistochemistry or Elisa method.
Measured: Cycle 1 days 1 and 15
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Jul 2007 (estimated)
- Study start14 Sep 2007
- Primary completion22 Apr 2010
- Study completion21 Jun 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Unspecified Adult Solid Tumor, Protocol SpecificStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 39 participants (actual)
Sponsor and investigators
- Lead sponsor
- NCIC Clinical Trials Group
- Sponsor type
- Research network
- Collaborators
- S*BIO
- Responsible party
- Sponsor
- Investigators
- Lillian L. Siu, MD, FRCPC, Study chair, Princess Margaret Hospital, Canada
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00504296
- Sponsor's protocol ID
- I188
- Other IDs
- CAN-NCIC-IND188, S*BIO-SB939-2007-002, CDR0000558934
- Status last verified
- Apr 2020
- First submitted
- 17 Jul 2007
- Last updated
- 4 Aug 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 21285985
Study at a glance
From the registry record, last updated by the sponsor on 4 Aug 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Clinical and Pharmacokinetic Study of SB939 in Patients With Advanced Cancer
- ClinicalTrials.gov ID
- NCT00504296
- Acronym / sponsor ID
- I188
- Keywords
- unspecified adult solid tumor, protocol specific
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 39 participants (actual)
- Lead sponsor
- NCIC Clinical Trials GroupResearch network
- Collaborators
- S*BIO
- Study start
- 14 Sep 2007 (actual)
- Primary completion
- 22 Apr 2010 (actual)
- Study completion
- 21 Jun 2011 (actual)
- First posted
- 19 Jul 2007 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| SB939 | Experimental | 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- Histologically or cytologically confirmed locally advanced or metastatic solid tumor
- 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
Key exclusion criteria (21 listed)
- Patients with documented CNS metastases
- Pathologic cardiac arrhythmia requiring active treatment
- Inability to take oral medication
- Pregnant or lactating women
- Women or men of child-bearing potential unless using effective contraception
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| HDAC inhibitor SB939SB939 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. | Drug | SB939 |
| immunoenzyme technique | Other | SB939 |
| immunohistochemistry staining method | Other | SB939 |
| immunologic technique | Other | SB939 |
| laboratory biomarker analysis | Other | SB939 |
| liquid chromatography | Other | SB939 |
| mass spectrometry | Other | SB939 |
| pharmacological study | Other | SB939 |
Primary outcome
Recommended phase II dose
Time frame: Each dose level
Assess for safety, tolerability, toxicity profile and dose limiting toxicities
3 secondary outcomes
Safety
Time frame: Each dose level
Pharmacokinetic profile
Time frame: Cycle 1 day 1 and 15
SB939 effects on histone H3 acetylation
Time frame: Cycle 1 days 1 and 15
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Aug 2023.
- Results publication: PubMed 21285985Razak 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.
- Individual participant dataSharing planned: No
Related trials for Unspecified Adult Solid Tumor, Protocol Specific
Active, not recruitingPhase 1
RNR Inhibitor COH29 in Treating Patients With Solid Tumors That Are Refractory to Standard Therapy or For Which No Standard Therapy Exists
Unspecified Adult Solid Tumor, Protocol Specific
Active, not recruiting
Assessment Tool for Older Patients With Cancer
Cognitive/Functional Effects, Psychosocial Effects of Cancer and Its Treatment
Active, not recruiting
Copper Cu 64 Anti-CEA Monoclonal Antibody M5A PET in Diagnosing Patients With CEA Positive Cancer
Breast Cancer, Colon Cancer
Recruiting
Copenhagen Prospective Personalized Oncology (CoPPO)
Unspecified Adult Solid Tumor, Protocol Specific
Active, not recruiting
3'-Deoxy-3'-[18F] Fluorothymidine PET Imaging in Patients With Cancer
Brain and Central Nervous System Tumors, Chronic Myeloproliferative Disorders
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Lillian L. Siu, MD, FRCPC study chair
Princess Margaret Hospital, Canada
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing HDAC inhibitor SB939, immunoenzyme technique and immunohistochemistry staining method in people with Unspecified Adult Solid Tumor, Protocol Specific, run by NCIC Clinical Trials Group at 2 sites in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 18 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Aug 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Recommended phase II dose (time frame: Each dose level). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00504296, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Aug 2023.