This trial is active, not recruiting.

Condition breast cancer
Treatment vorinostat
Phase phase 1/phase 2
Target HDAC
Sponsor National University Hospital, Singapore
Collaborator Merck Sharp & Dohme Corp.
Start date January 2007
End date January 2015
Trial size 49 participants
Trial identifier NCT00416130, BR05/24/06, DSRB Reference Code: B/06/275, HSA No: CTC0600314



- 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.

United States No locations recruiting
Other countries No locations recruiting

Study Design

Endpoint classification safety/efficacy study
Intervention model single group assignment
Masking open label
Primary purpose treatment
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.
vorinostat MK-0683
MK-0683 capsules, 100 mg, 400mg once a day, continuously (at dose level 0 - Phase 1 part of the study)

Primary Outcomes

Clinical laboratory tests
time frame: Screening (Visit 1) and weekly during Cycle 1
Vital signs
time frame: Screening (Visit 1) and at subsequent visits
time frame: (Visit 1) and every 12 weekly while on treatment.

Secondary Outcomes

Vorinostat concentration in serum samples
time frame: Cycle 1 Day 1 (Week 1) and Cycle 1 Day 15 (Week 3)
Level of histone H3 acetylation
time frame: Baseline and 3 weeks after initiation of Vorinostat treatment
Known functional single nucleotide polymorphisms
time frame: prior to start of treatment
Baseline plasma protein profiles and changes in response to chemotherapy
time frame: 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)
time frame: at baseline, and 3 weeks after initiation of Vorinostat treatment

Eligibility Criteria

Female participants at least 18 years old.

Key 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 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

Additional Information

Official title Phase I/II Clinical Trial of Vorinostat in Patients With Recurrent and/or Metastatic Breast Cancer
Description 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.
Trial information was received from ClinicalTrials.gov and was last updated in December 2013.
Information provided to ClinicalTrials.gov by National University Hospital, Singapore.