A Phase 1/2 interventional study of MK-0752, Docetaxel, Pegfilgrastim in Metastatic Breast Cancer, sponsored by University of Michigan Rogel Cancer Center. Completed at 3 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2014-04-04.
Sponsored by University of Michigan Rogel Cancer Center · Phase 1/2, Interventional, and Treatment
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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This study's enrollment of 30 is below the median of 72 across 9,494 interventional studies indexed under Breast Neoplasms.
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Exclusion Criteria:
MK-0752, Docetaxel, Pegfilgrastim in combination with escalating doses of MK-0752
Drug: MK-0752, Docetaxel, Pegfilgrastim
Drug pages: MK-0752 · Docetaxel · Pegfilgrastim
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
Also known as: Taxotere, Neulasta
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: 1. Non-hematologic toxicity Grade ≥3 by the NCI CTCAE version 3.0. 2. ANC\<1000 for more than 7 days despite use of pegfilgrastim. 3. Platelet count \<25,000 for more than 7 days, or associated with bleeding, or less than 10,000 at any time.
Time frame: 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.
Time frame: Up to 3 years
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.
| Milestone | MK-0752 and Docetaxel |
|---|---|
| Started | 30 |
| Completed | 30 |
| Not completed | 0 |
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: 1. Non-hematologic toxicity Grade ≥3 by the NCI CTCAE version 3.0. 2. ANC\<1000 for more than 7 days despite use of pegfilgrastim. 3. Platelet count \<25,000 for more than 7 days, or associated with bleeding, or less than 10,000 at any time.
| Dose Limiting Toxicities | MK-0752 and Docetaxel |
|---|---|
| Dose Limiting Toxicity (DLT) | 5 |
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.
| mg | MK-0752 and Docetaxel |
|---|---|
| Maximum Tolerated Dose (MTD) | 600 |
Collected over During therapy and for 30 days after therapy completion. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| MK-0752 | — | 16/30 (53.3%) | 30/30 (100%) |
| Event | MK-0752 |
|---|---|
| Device related infectionInfections and infestations | 2/30 |
| DiarrheaGastrointestinal disorders | 2/30 |
| DyspneaRespiratory, thoracic and mediastinal disorders | 2/30 |
| HypersensitivityGeneral disorders | 2/30 |
| Infection, Lung (pneumonia)Respiratory, thoracic and mediastinal disorders | 2/30 |
| Abdominal painGastrointestinal disorders | 1/30 |
| Alanine aminotransferase increasedInvestigations | 1/30 |
| Allergic rhinitisRespiratory, thoracic and mediastinal disorders | 1/30 |
| Autoimmune disorderImmune system disorders | 1/30 |
| BronchospasmRespiratory, thoracic and mediastinal disorders | 1/30 |
| Event | MK-0752 |
|---|---|
| FatigueGeneral disorders | 20/30 |
| NauseaGastrointestinal disorders | 15/30 |
| HemoglobinBlood and lymphatic system disorders | 11/30 |
| DiarrheaGastrointestinal disorders | 10/30 |
| HyperglycemiaMetabolism and nutrition disorders | 10/30 |
| Nail changesSkin and subcutaneous tissue disorders | 10/30 |
| HypocalcemiaMetabolism and nutrition disorders | 9/30 |
| HypokalemiaMetabolism and nutrition disorders | 9/30 |
| Alkaline phosphatase increasedInvestigations | 8/30 |
| Peripheral sensory neuropathyNervous system disorders | 8/30 |
| Age, Categorical(Participants) | MK-0752 and Docetaxel |
|---|---|
| <=18 years | 0 |
| Between 18 and 65 years | 25 |
| >=65 years | 5 |
| Sex: Female, Male(Participants) | MK-0752 and Docetaxel |
|---|---|
| Female | 30 |
| Male | 0 |
| Region of Enrollment(participants) | MK-0752 and Docetaxel |
|---|---|
| United States | 30 |
| Metastatic sites (multiple sites possible)(Participants) | MK-0752 and Docetaxel |
|---|---|
| Bone | 12 |
| Lung/Pleura | 16 |
| Liver | 13 |
| Lymph Nodes | 11 |
| Skin | 5 |
| Other | 7 |
| Number of Metastatic Sites(participants) | MK-0752 and Docetaxel |
|---|---|
| 0 | 4 |
| 1 | 6 |
| 2 | 6 |
| >=3 | 14 |
| Tumor Hormone Receptor Status(Participants) | MK-0752 and Docetaxel |
|---|---|
| ER positive/or PgR positive | 18 |
| ER negative and PgR negative | 12 |
| HER-2/neu status(Participants) | MK-0752 and Docetaxel |
|---|---|
| Negative | 28 |
| Positive | 2 |
| Prior Therapy For Metastatic Disease(Participants) | MK-0752 and Docetaxel |
|---|---|
| None | 7 |
| Chemotherapy | 7 |
| Hormonal Therapy | 0 |
| Chemotherapy and Hormonal Therapy | 16 |
1 further baseline measures are reported on the registry.
The record gives a start of Mar 2008, a primary completion of Jan 2010 and a completion of Oct 2012. It does not say whether these dates are actual or estimated.
Results were first posted in Apr 2014, 4 years 3 months after primary completion.
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This study is completed, as verified in Feb 2014. You cannot join it, but the record below documents what was studied.
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Studies of the drugs tested here: MK-0752 · Docetaxel · Pegfilgrastim
University of Michigan Rogel Cancer Center →