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| ID | Type | Description | Link |
|---|---|---|---|
| NYCC1 | Other Identifier | Montefiore Medical Center | |
| NCI-2013-01216 | Registry Identifier | CTRP |
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| Name | Class |
|---|---|
| Merck Sharp & Dohme LLC | INDUSTRY |
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Vorinostat is a histone deacetylase (HDAC) inhibitor which is approved by the U.S. Food and Drug Administration for the treatment of a rare type of cancer involving the skin (cutaneous T cell lymphoma), but not for breast cancer. HDAC inhibitors work by unsilencing tumor suppressor genes and other genes in the cancer cells that are repressed; when the genes are turned back on by the drug, it leads to death of the cancer cells. HDAC inhibitors such as vorinostat have been shown to enhance the effects of chemotherapy and trastuzumab in experimental systems. The purpose of this trial is to determine the optimal dose of vorinostat to use in combination with standard chemotherapy alone (or in combination with plus trastuzumab for HER2-positive disease), and to determine whether vorinostat enhances the effectiveness of standard chemotherapy (+/- trastuzumab) in patients with locally advanced breast cancer.
This is a phase I-II trial in which patients with stage IIB-IIIC breast cancer will receive:
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Vorinostat Plus Paclitaxel | Experimental | Vorinostat (PO days 1-3) plus weekly paclitaxel x 12 weeks (and trastuzumab if HER2-positive), followed by doxorubicin-cyclophosphamide every 2 weeks x 4 cycles, followed by surgery |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Vorinostat | Drug | Vorinostat 200 or 300 mg PO BID on days 1-3 of each weekly paclitaxel dose |
|
| Measure | Description | Time Frame |
|---|---|---|
| Recommended Phase II Dose of Vorinostat in Combination With Weekly Paclitaxel/Trastuzumab | Dose limiting toxicity in cycle 1 | 3 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Pathological Complete Response (CR) Rate in Patients With Her2/Neu Positive Locally Advanced Breast Cancer. | Pathological Complete Response (CR) defined as absence of invasive cancer at surgery | 6 months |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Joseph Sparano, MD | Montefiore Medical Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Montefiore Medical Center | The Bronx | New York | 10461 | United States |
Patients with HER2 positive disease also received trastuzumab.
Dates of recruitment: April 2008 - September 2013
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| ID | Title | Description |
|---|---|---|
| FG000 | Stratum A (HER2-positive): Dose Level 1 | Vorinostat (PO days 1-3) plus weekly paclitaxel x 12 weeks and trastuzumab x 12 weeks, followed by doxorubicin-cyclophosphamide every 2 weeks x 4 cycles, followed by surgery Vorinostat: Vorinostat 200 mg PO BID on days 1-3 of each weekly paclitaxel dose Paclitaxel: Paclitaxel 80 mg/m2 weekly for 12 weeks Trastuzumab: Trastuzumab (if HER2-positive) 4 mg/kg, then 2 mg/kg weekly for 12 weeks including loading dose Doxorubicin: Doxorubicin 60 mg/m2 every 2 weeks for 8 weeks Cyclophosphamide: Cyclophosphamide 600 mg/m2 every 2 weeks for 8 weeks Surgery: Surgical excision of tumor from breast |
| FG001 | Stratum A (HER2-positive): Dose Level 2 | Vorinostat (PO days 1-3) plus weekly paclitaxel x 12 weeks and trastuzumab x 12 weeks, followed by doxorubicin-cyclophosphamide every 2 weeks x 4 cycles, followed by surgery Vorinostat: Vorinostat 300 mg PO BID on days 1-3 of each weekly paclitaxel dose Paclitaxel: Paclitaxel 80 mg/m2 weekly for 12 weeks Trastuzumab: Trastuzumab (if HER2-positive) 4 mg/kg, then 2 mg/kg weekly for 12 weeks including loading dose Doxorubicin: Doxorubicin 60 mg/m2 every 2 weeks for 8 weeks Cyclophosphamide: Cyclophosphamide 600 mg/m2 every 2 weeks for 8 weeks Surgery: Surgical excision of tumor from breast |
| FG002 | Stratum B: Triple Negative | Vorinostat (PO days 1-3) plus weekly paclitaxel x 12 weeks and trastuzumab x 12 weeks, followed by doxorubicin-cyclophosphamide every 2 weeks x 4 cycles, followed by surgery Vorinostat: Vorinostat 300 mg PO BID on days 1-3 of each weekly paclitaxel dose Paclitaxel: Paclitaxel 80 mg/m2 weekly for 12 weeks Trastuzumab: Trastuzumab (if HER2-positive) 4 mg/kg, then 2 mg/kg weekly for 12 weeks including loading dose Doxorubicin: Doxorubicin 60 mg/m2 every 2 weeks for 8 weeks Cyclophosphamide: Cyclophosphamide 600 mg/m2 every 2 weeks for 8 weeks Surgery: Surgical excision of tumor from breast |
| FG003 | Stratum C: ER-Positive, HER2-negative | Vorinostat (PO days 1-3) plus weekly paclitaxel x 12 weeks and trastuzumab x 12 weeks, followed by doxorubicin-cyclophosphamide every 2 weeks x 4 cycles, followed by surgery Vorinostat: Vorinostat 300 mg PO BID on days 1-3 of each weekly paclitaxel dose Paclitaxel: Paclitaxel 80 mg/m2 weekly for 12 weeks Trastuzumab: Trastuzumab (if HER2-positive) 4 mg/kg, then 2 mg/kg weekly for 12 weeks including loading dose Doxorubicin: Doxorubicin 60 mg/m2 every 2 weeks for 8 weeks Cyclophosphamide: Cyclophosphamide 600 mg/m2 every 2 weeks for 8 weeks Surgery: Surgical excision of tumor from breast |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Stratum A (HER2-positive): Dose Level 1 | Vorinostat (PO days 1-3) plus weekly paclitaxel x 12 weeks and trastuzumab, followed by doxorubicin-cyclophosphamide every 2 weeks x 4 cycles, followed by surgery Vorinostat: Vorinostat 200 mg PO BID on days 1-3 of each weekly paclitaxel dose Paclitaxel: Paclitaxel 80 mg/m2 weekly for 12 weeks Trastuzumab: Trastuzumab (if HER2-positive) 4 mg/kg, then 2 mg/kg weekly for 12 weeks including loading dose Doxorubicin: Doxorubicin 60 mg/m2 every 2 weeks for 8 weeks Cyclophosphamide: Cyclophosphamide 600 mg/m2 every 2 weeks for 8 weeks Surgery: Surgical excision of tumor from breast |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Recommended Phase II Dose of Vorinostat in Combination With Weekly Paclitaxel/Trastuzumab | Dose limiting toxicity in cycle 1 | The recommended Phase II Dose of vorinostat was determined in Stratum A and B participants only. | Posted | Number | mg | 3 weeks |
|
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Stratum A (HER2-positive): Dose Level 1 | Vorinostat (PO days 1-3) plus weekly paclitaxel x 12 weeks and trastuzumab x 12 weeks, followed by doxorubicin-cyclophosphamide every 2 weeks x 4 cycles, followed by surgery Vorinostat: Vorinostat 200 mg PO BID on days 1-3 of each weekly paclitaxel dose Paclitaxel: Paclitaxel 80 mg/m2 weekly for 12 weeks Trastuzumab: Trastuzumab (if HER2-positive) 4 mg/kg, then 2 mg/kg weekly for 12 weeks including loading dose Doxorubicin: Doxorubicin 60 mg/m2 every 2 weeks for 8 weeks Cyclophosphamide: Cyclophosphamide 600 mg/m2 every 2 weeks for 8 weeks Surgery: Surgical excision of tumor from breast |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| pulmonary emobolism | Respiratory, thoracic and mediastinal disorders | CTCAE (2.0) | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Markenya Mirander | Montefiore Medical Center | 718-862-8840 | MMIRANDE@montefiore.org |
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| ID | Term |
|---|---|
| D001943 | Breast Neoplasms |
| ID | Term |
|---|---|
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D001941 | Breast Diseases |
| D012871 | Skin Diseases |
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| ID | Term |
|---|---|
| D000077337 | Vorinostat |
| D017239 | Paclitaxel |
| D000068878 | Trastuzumab |
| D004317 | Doxorubicin |
| D003520 | Cyclophosphamide |
| D013514 | Surgical Procedures, Operative |
| D008408 | Mastectomy |
| D015412 | Mastectomy, Segmental |
| ID | Term |
|---|---|
| D000813 | Anilides |
| D000577 | Amides |
| D009930 | Organic Chemicals |
| D000814 | Aniline Compounds |
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| Paclitaxel | Drug | Paclitaxel 80 mg/m2 weekly for 12 weeks |
|
|
| Trastuzumab | Drug | Trastuzumab (if HER2-positive) 4 mg/kg, then 2 mg/kg weekly for 12 weeks including loading dose |
|
|
| Doxorubicin | Drug | Doxorubicin 60 mg/m2 every 2 weeks for 8 weeks |
|
|
| Cyclophosphamide | Drug | Cyclophosphamide 600 mg/m2 every 2 weeks for 8 weeks |
|
|
| Surgery | Procedure | Surgical excision of tumor from breast |
|
|
| BG001 | Stratum A (HER2-positive): Dose Level 2 | Vorinostat (PO days 1-3) plus weekly paclitaxel x 12 weeks and trastuzumab, followed by doxorubicin-cyclophosphamide every 2 weeks x 4 cycles, followed by surgery Vorinostat: Vorinostat 300 mg PO BID on days 1-3 of each weekly paclitaxel dose Paclitaxel: Paclitaxel 80 mg/m2 weekly for 12 weeks Trastuzumab: Trastuzumab (if HER2-positive) 4 mg/kg, then 2 mg/kg weekly for 12 weeks including loading dose Doxorubicin: Doxorubicin 60 mg/m2 every 2 weeks for 8 weeks Cyclophosphamide: Cyclophosphamide 600 mg/m2 every 2 weeks for 8 weeks Surgery: Surgical excision of tumor from breast |
| BG002 | Stratum B: Triple Negative | Vorinostat (PO days 1-3) plus weekly paclitaxel x 12 weeks and trastuzumab, followed by doxorubicin-cyclophosphamide every 2 weeks x 4 cycles, followed by surgery Vorinostat: Vorinostat 300 mg PO BID on days 1-3 of each weekly paclitaxel dose Paclitaxel: Paclitaxel 80 mg/m2 weekly for 12 weeks Trastuzumab: Trastuzumab (if HER2-positive) 4 mg/kg, then 2 mg/kg weekly for 12 weeks including loading dose Doxorubicin: Doxorubicin 60 mg/m2 every 2 weeks for 8 weeks Cyclophosphamide: Cyclophosphamide 600 mg/m2 every 2 weeks for 8 weeks Surgery: Surgical excision of tumor from breast |
| BG003 | Stratum C: ER-Positive, HER2-Negative | Vorinostat (PO days 1-3) plus weekly paclitaxel x 12 weeks and trastuzumab, followed by doxorubicin-cyclophosphamide every 2 weeks x 4 cycles, followed by surgery Vorinostat: Vorinostat 300 mg PO BID on days 1-3 of each weekly paclitaxel dose Paclitaxel: Paclitaxel 80 mg/m2 weekly for 12 weeks Trastuzumab: Trastuzumab (if HER2-positive) 4 mg/kg, then 2 mg/kg weekly for 12 weeks including loading dose Doxorubicin: Doxorubicin 60 mg/m2 every 2 weeks for 8 weeks Cyclophosphamide: Cyclophosphamide 600 mg/m2 every 2 weeks for 8 weeks Surgery: Surgical excision of tumor from breast |
| BG004 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
Stratum B: 300 mg by mouth on days 1-3 plus weekly paclitaxel 80 mg x 12 weeks and trastuzumab 4 mg/kg, then 2 mg/kg x 12 weeks, followed by doxorubicin 60 mg/m2 -cyclophosphamide 600 mg/m2 every 2 weeks x 8 weeks, followed by surgery
|
|
| Secondary | Pathological Complete Response (CR) Rate in Patients With Her2/Neu Positive Locally Advanced Breast Cancer. | Pathological Complete Response (CR) defined as absence of invasive cancer at surgery | Stratum A (HER2-positive): Dose Level 1 and Stratum A (HER2-positive): Dose Level 2 are combined. Data was collected for outcome measures per stratum not per dose level. 2 pts in Stratum A were not evaluable (1 lost to f/u; 1 death); 1 pt was not evaluable in Stratum B (1 death) and 1 pt was not evaluable in C (1 declined surgery) | Posted | Count of Participants | Participants | 6 months |
|
|
|
|
| 0 |
| 3 |
| 0 |
| 3 |
| 0 |
| 3 |
| EG001 | Stratum A (HER2-positive): Dose Level 2 | Vorinostat (PO days 1-3) plus weekly paclitaxel x 12 weeks and trastuzumab x 12 weeks, followed by doxorubicin-cyclophosphamide every 2 weeks x 4 cycles, followed by surgery Vorinostat: Vorinostat 300 mg PO BID on days 1-3 of each weekly paclitaxel dose Paclitaxel: Paclitaxel 80 mg/m2 weekly for 12 weeks Trastuzumab: Trastuzumab (if HER2-positive) 4 mg/kg, then 2 mg/kg weekly for 12 weeks including loading dose Doxorubicin: Doxorubicin 60 mg/m2 every 2 weeks for 8 weeks Cyclophosphamide: Cyclophosphamide 600 mg/m2 every 2 weeks for 8 weeks Surgery: Surgical excision of tumor from breast | 1 | 23 | 2 | 23 | 0 | 23 |
| EG002 | Stratum B: Triple Negative | Vorinostat (PO days 1-3) plus weekly paclitaxel x 12 weeks and trastuzumab x 12 weeks, followed by doxorubicin-cyclophosphamide every 2 weeks x 4 cycles, followed by surgery Vorinostat: Vorinostat 300 mg PO BID on days 1-3 of each weekly paclitaxel dose Paclitaxel: Paclitaxel 80 mg/m2 weekly for 12 weeks Trastuzumab: Trastuzumab (if HER2-positive) 4 mg/kg, then 2 mg/kg weekly for 12 weeks including loading dose Doxorubicin: Doxorubicin 60 mg/m2 every 2 weeks for 8 weeks Cyclophosphamide: Cyclophosphamide 600 mg/m2 every 2 weeks for 8 weeks Surgery: Surgical excision of tumor from breast | 1 | 16 | 1 | 16 | 0 | 16 |
| EG003 | Stratum C: ER-Positive, HER2-negative | Vorinostat (PO days 1-3) plus weekly paclitaxel x 12 weeks and trastuzumab x 12 weeks, followed by doxorubicin-cyclophosphamide every 2 weeks x 4 cycles, followed by surgery Vorinostat: Vorinostat 300 mg PO BID on days 1-3 of each weekly paclitaxel dose Paclitaxel: Paclitaxel 80 mg/m2 weekly for 12 weeks Trastuzumab: Trastuzumab (if HER2-positive) 4 mg/kg, then 2 mg/kg weekly for 12 weeks including loading dose Doxorubicin: Doxorubicin 60 mg/m2 every 2 weeks for 8 weeks Cyclophosphamide: Cyclophosphamide 600 mg/m2 every 2 weeks for 8 weeks Surgery: Surgical excision of tumor from breast | 0 | 13 | 0 | 13 | 0 | 13 |
| cardiac tamponade | Cardiac disorders | CTCAE (2.0) | Systematic Assessment |
|
| congestive heart failure | Cardiac disorders | CTCAE (2.0) | Systematic Assessment |
|
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| D017437 |
| Skin and Connective Tissue Diseases |
| D000588 |
| Amines |
| D006877 | Hydroxamic Acids |
| D006898 | Hydroxylamines |
| D006880 | Hydroxy Acids |
| D002264 | Carboxylic Acids |
| D043823 | Taxoids |
| D043822 | Cyclodecanes |
| D003516 | Cycloparaffins |
| D006840 | Hydrocarbons, Alicyclic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D004224 | Diterpenes |
| D013729 | Terpenes |
| D061067 | Antibodies, Monoclonal, Humanized |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
| D003630 | Daunorubicin |
| D018943 | Anthracyclines |
| D009279 | Naphthacenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D006841 | Hydrocarbons, Aromatic |
| D011083 | Polycyclic Compounds |
| D000617 | Aminoglycosides |
| D006027 | Glycosides |
| D002241 | Carbohydrates |
| D010752 | Phosphoramide Mustards |
| D009588 | Nitrogen Mustard Compounds |
| D009150 | Mustard Compounds |
| D006846 | Hydrocarbons, Halogenated |
| D063088 | Phosphoramides |
| D009943 | Organophosphorus Compounds |