Metastatic Breast CancerPhase 1/2NCT00645333
Phase I/II Study of MK-0752 Followed by Docetaxel in Advanced or Metastatic Breast Cancer
A Phase 1/2 study testing MK-0752, Docetaxel, Pegfilgrastim in people with Metastatic Breast Cancer, run by University of Michigan Rogel Cancer Center at 3 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Breast Cancer
- What is being tested?
- MK-0752, Docetaxel, Pegfilgrastim
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 3 sitesUnited States
- Study dates
- Mar 2008to Oct 2012
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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)
Trial locations and contacts
3 sites in 1 country.
United States3 sites
University of Michigan Cancer Center
Ann Arbor, Michigan, 48109
Dana Farber Cancer Institute
Boston, Massachusetts, 02115
Baylor College of Medicine
Houston, Texas, 77030
About this study
Official title: 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
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.
Read the detailed description
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.
- Conditions
- Metastatic Breast Cancer
- Being tested
- MK-0752, Docetaxel, Pegfilgrastim
- Keywords
- breast cancer, Phase I clinical trial, cancer stem cells, agents with other mechanisms of action, Notch inhibitors
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MK-0752, Docetaxel, PegfilgrastimDrug
Also called Taxotere, Neulasta
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
| Study group | Role | What they receive |
|---|---|---|
| MK-0752, Docetaxel, Pegfilgrastim | Experimental | MK-0752, Docetaxel, Pegfilgrastim in combination with escalating doses of MK-0752 Receives: Drug: MK-0752, Docetaxel, Pegfilgrastim |
What is being measured
The primary outcome is the main question the study is designed to answer.
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:
- Non-hematologic toxicity Grade ≥3 by the NCI CTCAE version 3.0.
- ANC<1000 for more than 7 days despite use of pegfilgrastim.
- Platelet count <25,000 for more than 7 days, or associated with bleeding, or less than 10,000 at any time.
Measured: 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.
Measured: Up to 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Mar 2008 (estimated)
- Study startMar 2008
- Primary completionJan 2010
- Study completionOct 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Metastatic Breast CancerStudies of the same condition, open and under way.
- More trials run by University of Michigan Rogel Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Michigan Rogel Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- Baylor College of Medicine, Ohio State University, Dana-Farber Cancer Institute, Weill Medical College of Cornell University, Merck Sharp & Dohme LLC
- Responsible party
- Principal investigator, Ann Schott, MD, University of Michigan Rogel Cancer Center
- Investigators
- Anne Schott, MD, Principal investigator, The University of Michigan Comprehensive Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00645333
- Sponsor's protocol ID
- UMCC 2006.119
- Status last verified
- Feb 2014
- First submitted
- 24 Mar 2008
- Last updated
- 4 Apr 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 23340294
Study at a glance
From the registry record, last updated by the sponsor on 4 Apr 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT00645333
- Acronym / sponsor ID
- UMCC 2006.119
- Conditions
- Metastatic Breast Cancer
- Keywords
- breast cancer, Phase I clinical trial, cancer stem cells, agents with other mechanisms of action, Notch inhibitors
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- University of Michigan Rogel Cancer CenterUniversity, hospital or other
- Collaborators
- Baylor College of Medicine, Ohio State University, Dana-Farber Cancer Institute, Weill Medical College of Cornell University, Merck Sharp & Dohme LLC
- Study start
- Mar 2008
- Primary completion
- Jan 2010 (actual)
- Study completion
- Oct 2012 (actual)
- First posted
- 27 Mar 2008 (estimated)
- Results
- Posted 4 Apr 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| MK-0752, Docetaxel, Pegfilgrastim | Experimental | Drug: MK-0752, Docetaxel, PegfilgrastimMK-0752, Docetaxel, Pegfilgrastim in combination with escalating doses of MK-0752 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (6 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MK-0752, Docetaxel, PegfilgrastimAlso: Taxotere, NeulastaMK-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 | Drug | MK-0752, Docetaxel, Pegfilgrastim |
Primary outcome
Dose Limiting Toxicity (DLT)
Time frame: first 21 days
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.
Maximum Tolerated Dose (MTD)
Time frame: Up to 3 years
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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Apr 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 23340294Schott 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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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Anne Schott, MD principal investigator
The University of Michigan Comprehensive Cancer Center
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing MK-0752, Docetaxel, Pegfilgrastim in people with Metastatic Breast Cancer, run by University of Michigan Rogel Cancer Center at 3 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Apr 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 4 Apr 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Dose Limiting Toxicity (DLT) (time frame: first 21 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00645333, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Apr 2014.