NCT00416130

Brief Summary

Purpose:

  • evaluate the safety of Vorinostat.
  • evaluate the effectiveness of Vorinostat in treating breast cancer
  • evaluate how the study subject's body reacts to Vorinostat, how these reactions relate to the subject's genes, and whether protein changes in the subject blood may be used to predict how the subject's cancer will respond to Vorinostat We hypothesize that Vorinostat, as a novel class of anti-cancer agents, may induce response in patients with recurrent or metastatic breast cancer who have been previously treated with anthracyclines and taxanes. In addition, we hypothesize that serum Vorinostat levels may correlate with clinical response and toxicities, and that Vorinostat may induce unique protein changes in the plasma in responding patients, and that these proteins may in turn be used as predictive biomarkers for treatment response.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
49

participants targeted

Target at P50-P75 for phase_1 breast-cancer

Timeline
Completed

Started Jan 2007

Longer than P75 for phase_1 breast-cancer

Geographic Reach
1 country

2 active sites

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

December 26, 2006

Completed
1 day until next milestone

First Posted

Study publicly available on registry

December 27, 2006

Completed
5 days until next milestone

Study Start

First participant enrolled

January 1, 2007

Completed
8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 1, 2015

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

January 1, 2015

Completed
Last Updated

December 10, 2013

Status Verified

December 1, 2013

Enrollment Period

8 years

First QC Date

December 26, 2006

Last Update Submit

December 8, 2013

Conditions

Breast Cancer

Keywords

Phase I/II Clinical TrialVorinostatSAHARecurrent Breast CancerMetastatic Breast Cancer

Outcome Measures

Primary Outcomes (3)

  • Clinical laboratory tests

    Laboratory tests will include the following: full blood count, albumin, alkaline phosphatase, total bilirubin, BUN, calcium, chloride, creatinine, glucose, LDH, potassium, total protein, AST, ALT, sodium and uric acid

    Screening (Visit 1) and weekly during Cycle 1

  • Vital signs

    Vital signs will include pulse, blood pressure, temperature, and respiration rate. Any treatment-emergent clinically significant vital sign abnormalities should be reported and followed as an adverse event.

    Screening (Visit 1) and at subsequent visits

  • Electrocardiograms

    ECG results will be reviewed by the investigator, and any treatment-emergent clinically significant ECG abnormality should be reported and followed as an adverse event.

    (Visit 1) and every 12 weekly while on treatment.

Secondary Outcomes (5)

  • Vorinostat concentration in serum samples

    Cycle 1 Day 1 (Week 1) and Cycle 1 Day 15 (Week 3)

  • Level of histone H3 acetylation

    Baseline and 3 weeks after initiation of Vorinostat treatment

  • Known functional single nucleotide polymorphisms

    prior to start of treatment

  • Baseline plasma protein profiles and changes in response to chemotherapy

    baseline, on day 1 of each subsequent treatment cycle for the first 6 cycles, followed by 3 monthly until documented disease progression.

  • Tumor histone acetylation studies, genomics and proteomics studies (optional)

    at baseline, and 3 weeks after initiation of Vorinostat treatment

Study Arms (1)

Vorinostat

EXPERIMENTAL

A phase I portion that will determine the safety of 400mg Vorinostat once a day, continuously in the Asian population. A pre-determined dose reduction schema will be followed in the event of significant dose-limiting toxicities at this dose. Phase II will recruit additional patients at the determined dose with the goal of evaluating drug efficacy.

Drug: Vorinostat

Interventions

VorinostatDRUG

MK-0683 capsules, 100 mg, 400mg once a day, continuously (at dose level 0 - Phase 1 part of the study)

Also known as: MK-0683
Vorinostat

Eligibility Criteria

Age18 Years+
Sexfemale
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Cytologically or histologically confirmed adenocarcinoma of the breast that is recurrent and/or metastatic
  • Must have measurable disease as defined by RECIST criteria
  • No more than 2 prior chemotherapy for recurrent and/or metastatic disease excluding neoadjuvant or adjuvant chemotherapy
  • Previously received anthracycline- and taxane-containing chemotherapy for treatment of breast cancer in the neoadjuvant, adjuvant, or metastatic setting
  • Must be able to swallow capsules
  • Adequate bone marrow reserve and liver function
  • Women in reproductive age group must agree to practice effective contraception during the entire study period unless documentation of infertility exists.

You may not qualify if:

  • Prior treatment with any HDAC inhibitor. Patients who have received such agents for other indications, e.g. epilepsy, may enroll in the trial after a 30 day washout period.
  • Known CNS involvement by tumor
  • Concurrent use of oral retinoids or any vitamin A, other than a single multivitamin tablet daily
  • Acute infection requiring intravenous antibiotics or antifungal agents,known HIV infection, active hepatitis B and/or hepatitis C infection
  • Uncontrolled intercurrent illness
  • Cancer other than breast cancer with the exception of basal cell carcinoma or disease that has been in remission for ≥5 years
  • Pregnant or lactating women

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (2)

National University Hospital

Singapore, 149547, Singapore

Location

National Cancer Centre

Singapore, 169610, Singapore

Location

Related Publications (2)

  • Munster PN, Troso-Sandoval T, Rosen N, Rifkind R, Marks PA, Richon VM. The histone deacetylase inhibitor suberoylanilide hydroxamic acid induces differentiation of human breast cancer cells. Cancer Res. 2001 Dec 1;61(23):8492-7.

    PMID: 11731433BACKGROUND

  • Kelly WK, O'Connor OA, Krug LM, Chiao JH, Heaney M, Curley T, MacGregore-Cortelli B, Tong W, Secrist JP, Schwartz L, Richardson S, Chu E, Olgac S, Marks PA, Scher H, Richon VM. Phase I study of an oral histone deacetylase inhibitor, suberoylanilide hydroxamic acid, in patients with advanced cancer. J Clin Oncol. 2005 Jun 10;23(17):3923-31. doi: 10.1200/JCO.2005.14.167. Epub 2005 May 16.

    PMID: 15897550BACKGROUND

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Vorinostat

Condition Hierarchy (Ancestors)

Neoplasms by SiteNeoplasmsBreast DiseasesSkin DiseasesSkin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

AnilidesAmidesOrganic ChemicalsAniline CompoundsAminesHydroxamic AcidsHydroxylaminesHydroxy AcidsCarboxylic Acids

Study Officials

  • Soo Chin LEE, MBBS,MRCP

    National University Hospital, Singapore

    STUDY CHAIR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Dr. Lee Soo Chin

Study Record Dates

First Submitted

December 26, 2006

First Posted

December 27, 2006

Study Start

January 1, 2007

Primary Completion

January 1, 2015

Study Completion

January 1, 2015

Last Updated

December 10, 2013

Record last verified: 2013-12

Locations

SG(2)