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| Name | Class |
|---|---|
| Baylor College of Medicine | OTHER |
| Ohio State University | OTHER |
| Dana-Farber Cancer Institute | OTHER |
| Weill Medical College of Cornell University |
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New and better therapies for locally advanced and metastatic breast cancer are needed because, even if standard treatment is successful in shrinking the cancer, there is still a high chance that the cancer will recur. Recent research suggests that breast tumors have a small number of cells in them that are "breast cancer stem cells", which are very resistant to standard treatment. It is thought that the reason that many patients cannot be cured of their breast cancers is that the stem cells are unable to be killed and remain in the body after standard treatment. Laboratory research has shown that a new drug, MK-0752, can target stem cells and prevent tumor recurrences when the drug is combined with docetaxel, a chemotherapy drug commonly used to treat breast cancer.
We know that MK-0752 is safe when given by itself to people. We do not know if treatment with MK-0752 and docetaxel combined is safe or if it will kill "breast cancer stem cells" in people with breast cancer. This clinical trial is being done to determine the safety of several doses of MK-0752 in combination with docetaxel. Preliminary data about the effectiveness of MK-0752 in combination with docetaxel will be collected. Also, tumor biopsy samples will be taken from some patients who have tumors that can be easily biopsied. The samples will be used to perform research tests to help determine if the "breast cancer stem cells" are being killed by the drug combination.
Purpose-Accumulating evidence supports the existence of breast cancer stem cells (BCSCs), which are characterized by their capacity to self-renew and divide indefinitely, and resistance to conventional therapies. The Notch pathway is important for stem cell renewal, and is a potential target for BCSC-directed therapy. Experimental Design-Using human breast tumorgraft studies, we evaluated the impact of gamma secretase inhibitors (GSI) on the BCSC population and the efficacy of combining GSI with docetaxel treatment. The mouse experimental therapy paralleled a concurrent clinical trial in advanced breast cancer patients, designed to determine the maximally tolerated dose of the GSI, MK-0752, administered sequentially with docetaxel, and to evaluate BCSC markers in serial tumor biopsies.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| MK-0752, Docetaxel, Pegfilgrastim | Experimental | MK-0752, Docetaxel, Pegfilgrastim in combination with escalating doses of MK-0752 |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| MK-0752, Docetaxel, Pegfilgrastim | Drug | MK-0752 in escalating doses of 300, 450, 600, and 800 mg given orally on days 1-3, followed by docetaxel 80 mg/m2 day 8 and pegfilgrastim 6 mg SQ on day 9 |
| Measure | Description | Time Frame |
|---|---|---|
| Dose Limiting Toxicity (DLT) | The number of DLTs experienced by participants within the first 21 days. DLTs were defined as toxicities possibly, probably, or definitely related to the study drug observed during the first 2 cycles (first 42 days) as follows:
| first 21 days |
| Maximum Tolerated Dose (MTD) | The Maximum Tolerated Dose (MTD) for MK-0752 will be determined. Dose levels were: Level 1: 300 mg MK-0752 by mouth days 1-3; Level 2: 450 mg MK-0752 by mouth days 1-3; Level 3: 600 mg MK-0752 by mouth days 1-3; Level 4: 800 mg MK-0752 by mouth days 1-3. | Up to 3 years |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Anne Schott, MD | The University of Michigan Comprehensive Cancer Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Dana Farber Cancer Institute | Boston | Massachusetts | 02115 | United States | ||
| University of Michigan Cancer Center |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 23340294 | Result | Schott AF, Landis MD, Dontu G, Griffith KA, Layman RM, Krop I, Paskett LA, Wong H, Dobrolecki LE, Lewis MT, Froehlich AM, Paranilam J, Hayes DF, Wicha MS, Chang JC. Preclinical and clinical studies of gamma secretase inhibitors with docetaxel on human breast tumors. Clin Cancer Res. 2013 Mar 15;19(6):1512-24. doi: 10.1158/1078-0432.CCR-11-3326. Epub 2013 Jan 22. |
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There must b at least a 6 month interval since prior taxane therapy.
Eligible subjects included men or women with metastatic (Stage IV)breast cancer, or with locally advanced breast cancer (Stages IIIA> 10cm, or stages IIIB and IIIC) that did not respond to first-line anthracycline-based chemotherapy.
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| ID | Title | Description |
|---|---|---|
| FG000 | MK-0752 and Docetaxel | MK-0752 in escalating doses, orally days 1-3, followed by docetaxel 80 mg/m2 IV on day 8, and pegfilgrastim 6mg SQ day 9. Cycle repeated every 21 days. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | MK-0752 and Docetaxel | MK-0752 in escalating doses, orally days 1-3, followed by docetaxel 80 mg/m2 IV on day 8, and pegfilgrastim 6mg SQ day 9. Cycle repeated every 21 days. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| 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 | Dose Limiting Toxicity (DLT) | The number of DLTs experienced by participants within the first 21 days. DLTs were defined as toxicities possibly, probably, or definitely related to the study drug observed during the first 2 cycles (first 42 days) as follows:
| Posted | Number | Dose Limiting Toxicities | first 21 days |
|
During therapy and for 30 days after therapy completion
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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 | MK-0752 | MK-0752 in escalating doses, orally days 1-3, followed by docetaxel 80 mg/m2 IV on day 8, and pegfilgrastim 6mg SQ day 9. Cycle repeated every 21 days. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abdominal pain | Gastrointestinal disorders | Non-systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abdominal pain | Gastrointestinal disorders | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Anne F. Schott, MD | University of Michigan | 1-800-865-1125 | canceranswerline@umich.edu |
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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 |
|---|---|
| C554093 | 3-(4-((4-chlorophenyl)sulfonyl)-4-(2,5-difluorophenyl)cyclohexyl)propanoic acid |
| D000077143 | Docetaxel |
| C455861 | pegfilgrastim |
| ID | Term |
|---|---|
| D043823 | Taxoids |
| D043822 | Cyclodecanes |
| D003516 | Cycloparaffins |
| D006840 | Hydrocarbons, Alicyclic |
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| OTHER |
| Merck Sharp & Dohme LLC | INDUSTRY |
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|
| Ann Arbor |
| Michigan |
| 48109 |
| United States |
| Baylor College of Medicine | Houston | Texas | 77030 | United States |
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Metastatic sites (multiple sites possible) | Metastatic sites at baseline. Patients may have more than one metastatic site at baseline and therefore the total numbers for all categories (all metastatic sites) may be greater than the overall number of baseline participants. | Number | Participants |
|
| Number of Metastatic Sites | Number | participants |
|
| Tumor Hormone Receptor Status | Number | Participants |
|
| HER-2/neu status | Number | Participants |
|
| Prior Therapy For Metastatic Disease | Prior therapy for metastatic disease. Patients may have had more than one prior therapy and therefore the total numbers for all categories (all prior therapies) may be greater than the overall number of baseline participants. | Number | Participants |
|
| Number of Prior Metastatic Chemotherapy Regimens | Number of prior metastatic chemotherapy regimens. Patients may have more than one prior metastatic chemotherapy regimen and therefore the total numbers for all categories (all prior metastatic chemotherapy regimens) may be greater than the overall number of baseline participants. | Number | Participants |
|
| Units | Counts |
|---|
| Participants |
|
|
| Primary | Maximum Tolerated Dose (MTD) | The Maximum Tolerated Dose (MTD) for MK-0752 will be determined. Dose levels were: Level 1: 300 mg MK-0752 by mouth days 1-3; Level 2: 450 mg MK-0752 by mouth days 1-3; Level 3: 600 mg MK-0752 by mouth days 1-3; Level 4: 800 mg MK-0752 by mouth days 1-3. | Posted | Number | mg | Up to 3 years |
|
|
|
| 16 |
| 30 |
| 30 |
| 30 |
| Alanine aminotransferase increased | Investigations | Non-systematic Assessment |
|
| Allergic rhinitis | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
|
| Autoimmune disorder | Immune system disorders | Non-systematic Assessment |
|
| Bronchospasm | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
|
| Chest pain | Cardiac disorders | Non-systematic Assessment |
|
| Dermatology/Skin - Other (Specify) | Skin and subcutaneous tissue disorders | Non-systematic Assessment |
|
| Device related infection | Infections and infestations | Non-systematic Assessment |
|
| Diarrhea | Gastrointestinal disorders | Non-systematic Assessment |
|
| Disease progression | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | Non-systematic Assessment |
|
| Dyspnea | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
|
| Edema limbs | General disorders | Non-systematic Assessment |
|
| Fracture | Injury, poisoning and procedural complications | Non-systematic Assessment |
|
| Hand-and-foot syndrome | Nervous system disorders | Non-systematic Assessment |
|
| Hypersensitivity | General disorders | Non-systematic Assessment |
|
| Immune system disorder | Immune system disorders | Non-systematic Assessment |
|
| Infection, Lung (pneumonia) | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
|
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
|
| Pneumonitis | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
|
| Upper respiratory infection | Infections and infestations | Non-systematic Assessment |
|
| Alanine aminotransferase increased | Investigations | Non-systematic Assessment |
|
| Alkaline phosphatase increased | Investigations | Non-systematic Assessment |
|
| Allergic reaction | Immune system disorders | Non-systematic Assessment |
|
| Alopecia | Skin and subcutaneous tissue disorders | Non-systematic Assessment |
|
| Anorexia | Metabolism and nutrition disorders | Non-systematic Assessment |
|
| Aspartate aminotransferase increased | Investigations | Non-systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | Non-systematic Assessment |
|
| Bone pain | Musculoskeletal and connective tissue disorders | Non-systematic Assessment |
|
| Breast pain | Reproductive system and breast disorders | Non-systematic Assessment |
|
| Bronchitis | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
|
| Cardiac Arrhythmia - Other (Specify) | Cardiac disorders | Non-systematic Assessment |
|
| Constipation | Gastrointestinal disorders | Non-systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
|
| Depression | Psychiatric disorders | Non-systematic Assessment |
|
| Dermatology/Skin - Other (Specify) | Skin and subcutaneous tissue disorders | Non-systematic Assessment |
|
| Diarrhea | Gastrointestinal disorders | Non-systematic Assessment |
|
| Dry eye syndrome | Eye disorders | Non-systematic Assessment |
|
| Dry skin | Skin and subcutaneous tissue disorders | Non-systematic Assessment |
|
| Dyspnea | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
|
| Edema limbs | General disorders | Non-systematic Assessment |
|
| Fatigue | General disorders | Non-systematic Assessment |
|
| Fever | General disorders | Non-systematic Assessment |
|
| GI - Other (Specify) | Gastrointestinal disorders | Non-systematic Assessment |
|
| Hand-and-foot syndrome | Nervous system disorders | Non-systematic Assessment |
|
| Headache | Nervous system disorders | Non-systematic Assessment |
|
| Hemoglobin | Blood and lymphatic system disorders | Non-systematic Assessment |
|
| Hot flashes | Vascular disorders | Non-systematic Assessment |
|
| Hyperglycemia | Metabolism and nutrition disorders | Non-systematic Assessment |
|
| Hypoalbuminemia | Metabolism and nutrition disorders | Non-systematic Assessment |
|
| Hypocalcemia | Metabolism and nutrition disorders | Non-systematic Assessment |
|
| Hypokalemia | Metabolism and nutrition disorders | Non-systematic Assessment |
|
| Insomnia | Psychiatric disorders | Non-systematic Assessment |
|
| Joint pain | Musculoskeletal and connective tissue disorders | Non-systematic Assessment |
|
| Leukocytes | Blood and lymphatic system disorders | Non-systematic Assessment |
|
| Lymphopenia | Blood and lymphatic system disorders | Non-systematic Assessment |
|
| Nail changes | Skin and subcutaneous tissue disorders | Non-systematic Assessment |
|
| Nasal congestion | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
|
| Nausea | Gastrointestinal disorders | Non-systematic Assessment |
|
| Pain - Other | General disorders | Non-systematic Assessment |
|
| Peripheral sensory neuropathy | Nervous system disorders | Non-systematic Assessment |
|
| Pharyngolaryngeal pain | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
|
| Platelets | Blood and lymphatic system disorders | Non-systematic Assessment |
|
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | Non-systematic Assessment |
|
| Skin infection | Infections and infestations | Non-systematic Assessment |
|
| Sweating | General disorders | Non-systematic Assessment |
|
| Taste alteration | Nervous system disorders | Non-systematic Assessment |
|
| Upper respiratory infection | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
|
| Urinary tract infection | Renal and urinary disorders | Non-systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | Non-systematic Assessment |
|
| Watering eyes | Eye disorders | Non-systematic Assessment |
|
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| D017437 |
| Skin and Connective Tissue Diseases |
| D006844 |
| Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D004224 | Diterpenes |
| D013729 | Terpenes |