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Phase I/II Clinical Trial of Vorinostat in Patients With Recurrent and/or Metastatic Breast Cancer

Phase 1/Phase 2
18 Years
Open (Enrolling)
Breast Cancer

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Trial Information

Phase I/II Clinical Trial of Vorinostat in Patients With Recurrent and/or Metastatic Breast Cancer

Breast cancer is sensitive to a range of chemotherapeutics agents, but despite initial
sensitivity, resistance typically emerges, resulting in disease relapse or progression.
Exploration of novel classes of agents in the treatment of breast cancer is therefore in
urgent need. Vorinostat or SAHA, a potent inhibitor of histone deacetylase (HDAC) activity,
represents a novel class of anti-cancer agents in early stages of development. Vorinostat is
active in inducing differentiation, cell growth arrest, and/or apoptosis in a wide variety
of transformed cells in culture, and has shown activity against breast cancer in cell lines
and animal models. Exploratory pharmacokinetic analysis has demonstrated that oral
Vorinostat has excellent bioavailability. Oral Vorinostat has been administered to more than
300 patients enrolled in completed or ongoing clinical studies. The maximum tolerated dose
(MTD) is 400 mg q.d. or 200 mg b.i.d. continuously, or 300 mg b.i.d. x 3 consecutive days
per week. Dose-limiting toxicities (DLT) are non-hematologic (anorexia, dehydration,
diarrhea and fatigue), that resolve quickly once drug administration is interrupted. This
study will evaluate the safety and efficacy of Vorinostat in breast cancer patients who have
failed anthracyclines and taxanes, and if proven active, will add an important new class of
agents to the treatment armamentarium of breast cancer. The study will be divided into 2
phases: phase I to determine the MTD in our population, starting with 400mg q.d.
continuously, with progressive dose decrements in the event of DLT; and phase 2 to determine
efficacy of Vorinostat at MTD in 12-37 evaluable patients. Correlative studies
(pharmacokinetics, pharmacogenetics, plasma proteomics, tumor histone acetylation, genomics
and proteomics) will be carried out to identify markers that will predict treatment response
and/or toxicity to Vorinostat, to achieve the future goal of tailored therapy.


Inclusion Criteria:

- 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.

Key Exclusion Criteria:

- 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

- 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

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Clinical laboratory tests

Outcome Description:

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

Outcome Time Frame:

Screening (Visit 1) and weekly during Cycle 1

Safety Issue:


Principal Investigator


Investigator Role:

Study Chair

Investigator Affiliation:

National University Hospital, Singapore


Singapore: Domain Specific Review Boards

Study ID:




Start Date:

January 2007

Completion Date:

January 2013

Related Keywords:

  • Breast Cancer
  • Phase I/II Clinical Trial
  • Vorinostat
  • SAHA
  • Recurrent Breast Cancer
  • Metastatic Breast Cancer
  • Breast Neoplasms