Advanced Breast CancerPhase 1NCT00106145
A Notch Signalling Pathway Inhibitor for Patients With Advanced Breast Cancer (0752-014)
A Phase 1 study testing Comparator: MK0752, Notch Inhibitor, Comparator: MK0752, Notch Inhibitor - 450 mg and Comparator: MK0752, Notch Inhibitor - 3 days on, 4 off in people with Advanced Breast Cancer and Other Solid Tumors, run by Merck Sharp & Dohme LLC.
Trial summary
An investigational study to determine the safety/tolerability, and efficacy of a notch signaling pathway inhibitor in patients with metastatic or locally advanced breast cancer and other advanced solid tumors. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced Breast Cancer, Other Solid Tumors
- What is being tested?
- Comparator: MK0752, Notch Inhibitor, Comparator: MK0752, Notch Inhibitor - 450 mg and Comparator: MK0752, Notch Inhibitor - 3 days on, 4 off
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 103 participants
- Where
- No sites listed yet
- Study dates
- Apr 2005to Aug 2011
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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
- Women or men greater than or equal to 18 years of age
- ECOG status less than or equal to 2 (a measurement to determine your ability to perform daily activities)
- In Parts I, III, and IV, patient must have a histologically confirmed, metastatic or locally advanced solid tumor that has failed to respond to standard therapy, progressed despite standard therapy, or for which standard therapy does not exist. There is no limit on the number of prior treatment regimens
- In Part II, only breast cancer patients are eligible
- In Part V, only patients with Numb negative breast cancer (i.e., tumor shows Numb immunoreactivity in less than 10% of the neoplastic cells assessed) are eligible
- Patient has recovered from and is at least 2 weeks from previous antineoplastic therapy, including chemotherapy, biological therapy (including Herceptin), hormonal therapy, radiotherapy, or surgery
Who cannot join
- Patient has had an investigational treatment in the preceding 21 days
- Uncontrolled congestive heart failure or myocardial infarction (heart attack) within 3 months of study start
- History of hepatitis B or C or HIV
- Patient has the presence of clinically apparent central nervous system metastases or carcinomatous meningitis. Patients with CNS metastases who have completed a course of radiotherapy and are clinically stable in the judgment of the investigator are eligible
- Patients with "currently active" second malignancy, other than non-melanoma skin cancer, should not be enrolled. Patients are not considered to have a "currently active" malignancy if they have completed therapy for prior malignancy and are considered by their physician to be at <30% risk of relapse
About this study
Official title: A Phase I Study of MK0752, a Notch Inhibitor, in Patients With Metastatic or Locally Advanced Breast Cancer and Other Solid Tumors
An investigational study to determine the safety/tolerability, and efficacy of a notch signaling pathway inhibitor in patients with metastatic or locally advanced breast cancer and other advanced solid tumors.
- Conditions
- Advanced Breast Cancer, Other Solid Tumors
- Being tested
- Comparator: MK0752, Notch Inhibitor, Comparator: MK0752, Notch Inhibitor - 450 mg, Comparator: MK0752, Notch Inhibitor - 3 days on, 4 off, Comparator: MK0752, Notch Inhibitor - 1 day on, 6 off, Comparator: MK0752, Notch Inhibitor - 3 days on, 4 off 350 mg
- Keywords
- Advanced Breast Cancer, Solid Tumors, Advanced Solid Tumors
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Comparator: MK0752, Notch InhibitorDrug
Dose escalating beginning with rising dose levels of 300, 450, and 600 mg/day in a continuous dosing schedule.
Comparator: MK0752, Notch Inhibitor - 450 mgDrug
Dose 450 mg capsules daily for 28 day cycles.
Comparator: MK0752, Notch Inhibitor - 3 days on, 4 offDrug
Dose escalating in a repeating intermittent dosing schedule of 3 days on and 4 days off at rising dose levels of 450, 600, 800, 1000, 1200, and 1400 mg/day.
Comparator: MK0752, Notch Inhibitor - 1 day on, 6 offDrug
Dose escalating in a repeating intermittent dosing schedule of 1 day on/6 days off at rising dose levels of 600, 900, 1200, 1500, 1800, 2400, 3200 mg/day once weekly and then increase at 33% increments.
Comparator: MK0752, Notch Inhibitor - 3 days on, 4 off 350 mgDrug
Dose 350 mg capsules daily intermittent 3 days on/4 days off dosing. THIS DOSING SCHEDULE IS NO LONGER UNDER INVESTIGATION
| Study group | Role | What they receive |
|---|---|---|
| Part I - Arm 1 | Experimental | Not described Receives: Drug: Comparator: MK0752, Notch Inhibitor |
| Part II - Arm 1 | Experimental | Not described Receives: Drug: Comparator: MK0752, Notch Inhibitor - 450 mg |
| Part III - Arm 1 | Experimental | Not described Receives: Drug: Comparator: MK0752, Notch Inhibitor - 3 days on, 4 off |
| Part IV - Arm 1 | Experimental | Not described Receives: Drug: Comparator: MK0752, Notch Inhibitor - 1 day on, 6 off |
| Part V - Arm 1 | Experimental | Not described Receives: Drug: Comparator: MK0752, Notch Inhibitor - 3 days on, 4 off 350 mg |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety and tolerability; MTD will be established
Measured: Day 1 to Day 28
Secondary outcomes (1)
Overall tumor/disease response will be evaluated using RECIST criteria, radiographic and clinical evaluations
Measured: radigraphic evaluation = every 56 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Mar 2005 (estimated)
- Study startApr 2005
- Primary completionAug 2011
- Study completionAug 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Advanced Breast CancerStudies of the same condition, open and under way.
- More trials run by Merck Sharp & Dohme LLCThe 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
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 103 participants (actual)
Sponsor and investigators
- Lead sponsor
- Merck Sharp & Dohme LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Monitor, Study director, Merck Sharp & Dohme LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00106145
- Sponsor's protocol ID
- 0752-014
- Other IDs
- 2005_008
- Status last verified
- Jan 2015
- First submitted
- 21 Mar 2005
- Last updated
- 30 Jan 2015
- Results posted
- No
Publications
Krop I, Demuth T, Guthrie T, Wen PY, Mason WP, Chinnaiyan P, Butowski N, Groves MD, Kesari S, Freedman SJ, Blackman S, Watters J, Loboda A, Podtelezhnikov A, Lunceford J, Chen C, Giannotti M, Hing J, Beckman R, Lorusso P. Phase I pharmacologic and pharmacodynamic study of the gamma secretase (Notch) inhibitor MK-0752 in adult patients with advanced solid tumors. J Clin Oncol. 2012 Jul 1;30(19):2307-13. doi: 10.1200/JCO.2011.39.1540. Epub 2012 Apr 30.
PubMed 22547604
Study at a glance
From the registry record, last updated by the sponsor on 30 Jan 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Study of MK0752, a Notch Inhibitor, in Patients With Metastatic or Locally Advanced Breast Cancer and Other Solid Tumors
- ClinicalTrials.gov ID
- NCT00106145
- Acronym / sponsor ID
- 0752-014
- Conditions
- Advanced Breast Cancer, Other Solid Tumors
- Keywords
- Advanced Breast Cancer, Solid Tumors, Advanced Solid Tumors
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 103 participants (actual)
- Lead sponsor
- Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
- Study start
- Apr 2005
- Primary completion
- Aug 2011 (actual)
- Study completion
- Aug 2011 (actual)
- First posted
- 22 Mar 2005 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
An investigational study to determine the safety/tolerability, and efficacy of a notch signaling pathway inhibitor in patients with metastatic or locally advanced breast cancer and other advanced solid tumors.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Part I - Arm 1 | Experimental | Drug: Comparator: MK0752, Notch Inhibitor |
| Part II - Arm 1 | Experimental | Drug: Comparator: MK0752, Notch Inhibitor - 450 mg |
| Part III - Arm 1 | Experimental | Drug: Comparator: MK0752, Notch Inhibitor - 3 days on, 4 off |
| Part IV - Arm 1 | Experimental | Drug: Comparator: MK0752, Notch Inhibitor - 1 day on, 6 off |
| Part V - Arm 1 | Experimental | Drug: Comparator: MK0752, Notch Inhibitor - 3 days on, 4 off 350 mg |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Women or men greater than or equal to 18 years of age
- ECOG status less than or equal to 2 (a measurement to determine your ability to perform daily activities)
- In Parts I, III, and IV, patient must have a histologically confirmed, metastatic or locally advanced solid tumor that has failed to respond to standard therapy, progressed despite standard therapy, or for which standard therapy does not exist. There is no limit on the number of prior treatment regimens
- In Part II, only breast cancer patients are eligible
- In Part V, only patients with Numb negative breast cancer (i.e., tumor shows Numb immunoreactivity in less than 10% of the neoplastic cells assessed) are eligible
Key exclusion criteria (5 listed)
- Patient has had an investigational treatment in the preceding 21 days
- Uncontrolled congestive heart failure or myocardial infarction (heart attack) within 3 months of study start
- History of hepatitis B or C or HIV
- Patient has the presence of clinically apparent central nervous system metastases or carcinomatous meningitis. Patients with CNS metastases who have completed a course of radiotherapy and are clinically stable in the judgment of the investigator are eligible
- Patients with "currently active" second malignancy, other than non-melanoma skin cancer, should not be enrolled. Patients are not considered to have a "currently active" malignancy if they have completed therapy for prior malignancy and are considered by their physician to be at <30% risk of relapse
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 |
|---|---|---|
| Comparator: MK0752, Notch InhibitorDose escalating beginning with rising dose levels of 300, 450, and 600 mg/day in a continuous dosing schedule. | Drug | Part I - Arm 1 |
| Comparator: MK0752, Notch Inhibitor - 450 mgDose 450 mg capsules daily for 28 day cycles. | Drug | Part II - Arm 1 |
| Comparator: MK0752, Notch Inhibitor - 3 days on, 4 offDose escalating in a repeating intermittent dosing schedule of 3 days on and 4 days off at rising dose levels of 450, 600, 800, 1000, 1200, and 1400 mg/day. | Drug | Part III - Arm 1 |
| Comparator: MK0752, Notch Inhibitor - 1 day on, 6 offDose escalating in a repeating intermittent dosing schedule of 1 day on/6 days off at rising dose levels of 600, 900, 1200, 1500, 1800, 2400, 3200 mg/day once weekly and then increase at 33% increments. | Drug | Part IV - Arm 1 |
| Comparator: MK0752, Notch Inhibitor - 3 days on, 4 off 350 mgDose 350 mg capsules daily intermittent 3 days on/4 days off dosing. THIS DOSING SCHEDULE IS NO LONGER UNDER INVESTIGATION | Drug | Part V - Arm 1 |
Primary outcome
Safety and tolerability; MTD will be established
Time frame: Day 1 to Day 28
1 secondary outcome
Overall tumor/disease response will be evaluated using RECIST criteria, radiographic and clinical evaluations
Time frame: radigraphic evaluation = every 56 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Jan 2015.
- Results publication: PubMed 22547604Krop I, Demuth T, Guthrie T, Wen PY, Mason WP, Chinnaiyan P, Butowski N, Groves MD, Kesari S, Freedman SJ, Blackman S, Watters J, Loboda A, Podtelezhnikov A, Lunceford J, Chen C, Giannotti M, Hing J, Beckman R, Lorusso P. Phase I pharmacologic and pharmacodynamic study of the gamma secretase (Notch) inhibitor MK-0752 in adult patients with advanced solid tumors. J Clin Oncol. 2012 Jul 1;30(19):2307-13. doi: 10.1200/JCO.2011.39.1540. Epub 2012 Apr 30.
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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.
Medical Monitor study director
Merck Sharp & Dohme LLC
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Comparator: MK0752, Notch Inhibitor, Comparator: MK0752, Notch Inhibitor - 450 mg and Comparator: MK0752, Notch Inhibitor - 3 days on, 4 off in people with Advanced Breast Cancer and Other Solid Tumors, run by Merck Sharp & Dohme LLC.
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 5 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 30 Jan 2015. Status can change between updates, so confirm with the study contact before making plans.
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 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.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Safety and tolerability; MTD will be established (time frame: Day 1 to Day 28). 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 NCT00106145, 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 30 Jan 2015.