Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Symptoms and General Pathology

Breast Neoplasms

Neoplasm Metastasis

Breast Diseases

Skin Diseases

Bone Density Conservation Agents

Antineoplastic Agents

All Drugs and Chemicals

Anticoagulants

Other Dietary Supplements

Tamoxifen

Estrogens

Citric Acid

Sodium Citrate

Selective Estrogen Receptor Modulators

Estrogen Receptor Modulators

Aromatase Inhibitors

Progesterone

Vorinostat

Estrogen Antagonists

Estrogen Receptor Antagonists

Hormones

Hormone Antagonists

Antineoplastic Agents, Hormonal

Histone Deacetylase Inhibitors

Enzyme Inhibitors

Citrate

Vorinostat will be used to potentiate the effects of tamoxifen or overcome tamoxifen resistance. All patients will receive vorinostat at 400 mg by mouth (po) daily for 3 out of 4 weeks. Responses will be assessed after 2 cycles (8 weeks + 4 days).

suberoylanilide hydroxamic acid (SAHA, Vorinostat)

Tamoxifen will be given once daily at 20 mg. Tamoxifen will be given continuously. Responses will be assessed after 2 cycles (8 weeks + 4 days).

tamoxifen citrate (Tamoxifen)

Susan Minton, D.O.

Phase II trial to explore the efficacy of vorinostat and tamoxifen combined.

Phase II trial to explore the efficacy of vorinostat and tamoxifen combined. Tamoxifen will be given once daily, continuously. Vorinostat will be given daily for 3 out of 4 weeks (a cycle). Responses will be assessed (restaged) after 2 cycles and toxicities will be captured continuously. Eligible patients will receive treatment in consecutive 4-week cycles, until progression of disease or unacceptable toxicity. Patients will be followed for evaluation of safety for at least 30 days after the last dose of the study drug.

Tests will be obtained pre-and post vorinostat treatment and correlated with plasma levels of vorinostat at the time of tumor biopsy and vorinostat doses; the tests will consist of:

* Patient history
* Physical exam (including height and weight)
* Toxicity assessment
* Pharmacokinetic (PK) sample
* Tumor fine needle aspirate (FNA)
* Peripheral Blood Mononuclear Cells (PBMC)
* Standard labs and Chemistry Profile
* Carcinoembryonic antigen (CEA), cancer antigen (Ca) 15-3, Ca 125 (If clinically indicated)
* Pregnancy Test
* Computed tomography (CT) scans, and magnetic resonance imaging (MRI)

Documentation of response and progression will be evaluated in this study using the Response Evaluation Criteria in Solid Tumors (RECIST).

Phase II Trial of SAHA & Tamoxifen for Patients With Breast Cancer

Phase II Trial of Suberoylanilide Hydroxamic Acid (SAHA, Vorinostat) in Combination With Tamoxifen for Patients With Advanced Breast Cancer Who Have Failed Prior Anti-hormonal Therapy.

The Objective Response Rate. Response and progression were evaluated in this study using the new international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST). Changes in only the largest diameter (unidimensional measurement) of the tumor lesions are used in the RECIST criteria. For the purposes of this study, patients were evaluated for response every 8 weeks. In addition to a baseline scan, confirmatory scans were also obtained ≥ 4 weeks following initial documentation of objective response.

The median response duration in months. Response and progression were evaluated in this study using the new international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST).

Safety evaluation according to descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0.

Merck Sharp & Dohme LLC

H. Lee Moffitt Cancer Center and Research Institute

Vorinostat and Tamoxifen as outlined in Intervention Descriptions

Vorinostat and Tamoxifen

Age, Categorical

Age, Customized

Sex: Female, Male

United States

Region of Enrollment

Number of Participants With Objective Response (OR)

Time to Progression (TTP)

Number of Participants With Serious Adverse Events (SAEs)

Overall Study

Respiratory Tract (Lung and Bronchial) Diseases

Blood and Lymph Conditions

Carcinoma

Mediastinal Neoplasms

Thymoma

Thymus Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Thoracic Neoplasms

Lymphatic Diseases

Belinostat

1000 mg/m\^2/day as a 30 minute intravenous (IV) infusion daily for 5 days every 3 weeks (day 1-5 of the 3 week treatment cycle). After 12 cycles of treatment, cycles will be given for 5 days every 4 weeks.

Belinostat (PDX101)

Giuseppe Giaccone, M.D.

Background:

* Cisplatin-containing chemotherapy is the standard treatment for advanced tumors of the thymus that cannot be removed surgically.
* New treatment options are needed for patients with advanced tumors of the thymus that do not improve with cisplatin-containing therapy.
* Belinostat is a drug that inhibits enzymes called histone deacetylase. Histone deacetylase inhibitors have shown promising activity in many cancers and may be useful in treating patients with thymic tumors.

Objectives:

-To assess the safety and effectiveness of belinostat for treatment of malignant thymic tumors in patients who failed after standard treatment.

Eligibility:

-Patients 18 years of age or older with an advanced thymic tumor that has progressed after treatment with platinum-containing chemotherapy.

Design:

* Patients receive belinostat treatment in 21-day cycles. The drug is given as an infusion through a vein during days 1 through 5 of each cycle. Treatment cycles continue as long as the medicine is tolerated and the cancer does not worsen.
* Patients have a physical examination and several blood tests during every cycle.
* Patients have an electrocardiogram every cycle before starting the belinostat infusion and again on the last day of the infusion.
* Patients undergo computed tomography (CT) or other imaging test, such as ultrasound or MRI, every two cycles to evaluate the response of the tumor to treatment.
* Tumor tissue obtained from a previous biopsy is used for research purposes.

Background:

Cisplatin-containing chemotherapy is the standard of care for advanced unresectable thymoma and thymic carcinoma. New options for treatment are necessary in patients with advanced thymoma and thymic carcinoma that have progressed on cisplatin-containing therapy. Histone deacetylase inhibitors have shown promising clinical activity in many malignancies. Belinostat, a potent histone deacetylase inhibitor, is a promising agent, which may have activity in patients with thymic malignancies.

Objectives:

* To assess objective response rate according to the Response Evaluation Criteria in Solid Tumors (RECIST) criteria for belinostat monotherapy.
* To assess safety of belinostat.
* To evaluate time to response, duration of response, progression-free survival and overall survival.
* To identify chromosomal gains or losses and gene methylation status by comparative genomic hybridization and methylation microarrays in thymoma / thymic carcinomas in relation to clinical outcome.
* To assess expression levels of particular proteins on the pretreatment tumor sample, by immunohistochemistry (IHC) and correlate them with clinical outcome.
* To identify and measure changes in p21 and protein hyperacetylation in peripheral blood mononuclear cells (PBMC), and vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in plasma and correlate them with clinical outcome.
* To measure changes in modulation of T-cell function in peripheral blood lymphocytes.

Eligibility:

* Patients with histologically confirmed thymic carcinoma or thymoma who have previously been treated on at least one platinum containing chemotherapy regimen.
* Measurable disease by RECIST criteria.
* Adequate renal, hepatic and hematopoietic function.
* QT Interval must be less than 500 msec at baseline by electrocardiogram (EKG) (Fridericia's formula used for correction).
* No major surgery, radiotherapy, or chemotherapy within 28 days of belinostat therapy.

Design:

* Patients will receive belinostat as a 30-minute intravenous (IV) infusion of 1000 mg/m\^2/day during days 1-5 every 3 weeks. After 12 cycles of treatment, cycles will be given every 4 weeks.
* Treatment with belinostat alone will continue until disease progression.
* Toxicity will be assessed every cycle by the Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 until December 31, 2010, and by CTCAE Version 4.0 beginning January 1, 2011.
* Tumor response assessments by RECIST criteria will be performed every 2 cycles. After 12 cycles, response assessment will be every 3 cycles.
* Correlative studies including comparative genomic hybridization, methylation microarray analysis, and tissue immunohistochemistry studies will be done on existing tumor blocks.
* Blood samples for circulating plasma biomarkers of response including VEGF will be drawn the first day of cycle 1 and 2 as well as cycle 1, day 3.
* Blood samples for protein hyperacetylation and T cell modulation analyses will be drawn the first day of cycle 1 and 2.

Belinostat (PXD101) to Treat Tumors of the Thymus at an Advanced Stage

A Multicenter Phase II Study of Belinostat (PXD-101) in Previously Chemotherapy Treated Thymoma and Thymic Carcinoma

Response is defined by the Response Evaluation Criteria in Solid Tumor (RECIST). Partial response (PR) is at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD. For additional details about the RECIST criteria see the protocol Link module.

Utilize a patients tumor tissue to determine if there is any correlation between chromosomal gains or losses in comparative genomic hybridization in thymoma and thymic carcinomas and clinical outcomes.

Here are the number of participants with adverse events. For a detailed list of adverse events see the adverse event module.

National Cancer Institute (NCI)

Principal Investigator

CTCAE v3.0 from beginning of study through 12/31/10; CTCAE v4.0 beginning 1/1/11.

Belinostat Treatment

Age, Continuous

Arun Rajan, M.D.

Thymoma Patients

Thymic Patients

Number of Participants With a Partial Response

1000 mg/m\^2 day, 30 minute intravenous infusion daily for 5 days every 3 weeks (day 1-5 of the 3 week treatment cycle). After 12 cycles of treatment, cycles will be given for 5 days every 4 weeks.

Number of Participants With Adverse Events

Unpublished data from Dr. Giaccone's lab does not reveal an association between these parameters and outcomes in patients with thymic malignancies. Hence we do not plan to perform analyses for these outcome measures and there is no known negative clinical implications associated with this.

Chromosomal Gains or Losses in Comparative Genomic Hydridization in Thymoma and Thymic Cancer

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Phase II Trial of SAHA & Tamoxifen for Patients With Breast Cancer	NCT00365599	Breast Cancer	suberoylanilide... tamoxifen citra...	18 Years -	H. Lee Moffitt Cancer Center and Research Institute
Belinostat (PXD101) to Treat Tumors of the Thymus at an Advanced Stage	NCT00589290	Thymoma Thymic Carcinom...	Belinostat (PDX...	18 Years -	National Institutes of Health Clinical Center (CC)
Belinostat (PXD101) to Treat Tumors of the Thymus at an Advanced Stage	NCT00589290	Thymoma Thymic Carcinom...	Belinostat (PDX...	18 Years -	National Institutes of Health Clinical Center (CC)

Spots Global Cancer Trial Database for histone deacetylase (hdac) inhibitors