Phase I/II Study of MK-0752 Followed by Docetaxel in Advanced or Metastatic Breast Cancer
Phase I/II Trial of MK-0752 Followed by Docetaxel in Locally Advanced or Metastatic Breast Cancer: A Study by the Stem Cell Clinical Consortium
1 other identifier
interventional
30
1 country
3
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_1
Started Mar 2008
Longer than P75 for phase_1
3 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
March 1, 2008
CompletedFirst Submitted
Initial submission to the registry
March 24, 2008
CompletedFirst Posted
Study publicly available on registry
March 27, 2008
CompletedPrimary Completion
Last participant's last visit for primary outcome
January 1, 2010
CompletedStudy Completion
Last participant's last visit for all outcomes
October 1, 2012
CompletedResults Posted
Study results publicly available
April 4, 2014
CompletedApril 4, 2014
February 1, 2014
1.8 years
March 24, 2008
August 9, 2013
February 24, 2014
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
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.
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
Study Arms (1)
MK-0752, Docetaxel, Pegfilgrastim
EXPERIMENTALMK-0752, Docetaxel, Pegfilgrastim in combination with escalating doses of MK-0752
Interventions
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
Eligibility Criteria
You may qualify if:
- Men or women with metastatic (Stage IV) breast cancer, or with locally advanced breast cancer (Stages IIIA \> 10 cm, or Stages IIIB and IIIC) that did not respond to first-line anthracycline-based chemotherapy, for whom docetaxel is a recommended therapy
- Presence of measurable or evaluable disease
- Adequate organ function
- Ability to swallow intact study drug capsules
- Zubrod Performance Status of 0-1 with at least a 3 month life expectancy
- Appropriate time must have elapsed since prior anti-neoplastic therapy with resolution of acute toxicity
You may not qualify if:
- Concurrent treatment with hormonal therapy intended to treat cancer
- Radiotherapy within 7 days prior to first dose
- Symptomatic central nervous system, and/or epidural metastases or symptomatic carcinomatous meningitis or with radiation treatment completed within the past 8 weeks
- Serious comorbid illness which will limit the ability of the patient to safely receive anticancer treatment
- Patients who are pregnant or nursing
- Confounding factors present to provide misinterpretation of data (i.e., concurrent malignancy)
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- University of Michigan Rogel Cancer Centerlead
- Baylor College of Medicinecollaborator
- Ohio State Universitycollaborator
- Dana-Farber Cancer Institutecollaborator
- Weill Medical College of Cornell Universitycollaborator
- Merck Sharp & Dohme LLCcollaborator
Study Sites (3)
Dana Farber Cancer Institute
Boston, Massachusetts, 02115, United States
University of Michigan Cancer Center
Ann Arbor, Michigan, 48109, United States
Baylor College of Medicine
Houston, Texas, 77030, United States
Related Publications (1)
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.
PMID: 23340294RESULT
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Anne F. Schott, MD
- Organization
- University of Michigan
Study Officials
- PRINCIPAL INVESTIGATOR
Anne Schott, MD
The University of Michigan Comprehensive Cancer Center
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- No
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Principal Investigator
Study Record Dates
First Submitted
March 24, 2008
First Posted
March 27, 2008
Study Start
March 1, 2008
Primary Completion
January 1, 2010
Study Completion
October 1, 2012
Last Updated
April 4, 2014
Results First Posted
April 4, 2014
Record last verified: 2014-02