Estrogen Receptor-positive Breast CancerPhase 1NCT01208441
RO4929097 and Letrozole in Treating Post-Menopausal Women With Hormone Receptor-Positive Stage II or Stage III Breast Cancer
A Phase 1 study testing letrozole, gamma-secretase/Notch signalling pathway inhibitor RO4929097 and therapeutic conventional surgery in people with Estrogen Receptor-positive Breast Cancer and HER2-negative Breast Cancer, run by National Cancer Institute (NCI) at 3 sites in United States.
Trial summary
This phase I trial is studying the side effects and best dose of RO4929097 when given together with letrozole in treating post-menopausal women with stage II or stage III breast cancer. RO4929097 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Estrogen Receptor-positive Breast Cancer, HER2-negative Breast Cancer, Progesterone Receptor-positive Breast Cancer
- What is being tested?
- letrozole, gamma-secretase/Notch signalling pathway inhibitor RO4929097 and therapeutic conventional surgery
- Type of treatment
- Pill or oral medicine, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 28 participants
- Where
- 3 sitesUnited States
- Study dates
- Nov 2010to Dec 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
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Pathologically confirmed invasive breast cancer
- Stage II or III disease (T2-T3, N0-2)
- No N3, T4 disease
- Estrogen receptor-positive (ER+) and/or progesterone receptor-positive (PR+)
- H score ≥ 10 or positivity ≥ 10%
- HER2 negative as determined by IHC (1 or 2+) or FISH (< 2.0+)
Show all 47Show fewer
- Bilateral disease allowed as long as all tumors are ER+ and ≥ 1 is T2-T3
- Patient must have disease that is palpable on physical exam and able to be imaged via breast ultrasound
- Defined as ≥ 1 T2 tumor > 2 cm
- Multifocal disease allowed provided that ≥ 1 of the tumors is > 2 cm
- No metastatic disease by CT scans of the chest, abdomen, and pelvis, a PET/CT bone scan, or nuclear medicine bone scan
- No inflammatory breast cancer or presence of breast tumor cells in the dermal lymphatics of the breast
- Post-menopausal meeting 1 of the following criteria:
- Bilateral oophorectomy
- Age ≥ 50 years and amenorrheic for > 12 months in the absence of chemotherapy, tamoxifen, toremifene, or ovarian suppression (spontaneous amenorrhea)
- ECOG performance status (PS) 0-2 (Karnofsky PS 60-100%)
- Life expectancy > 3 months
- ANC ≥ 1,000/mm³
- Platelet count ≥ 100,000/mm³
- Hemoglobin ≥ 9 g/dL
- Total bilirubin normal
- AST and ALT ≤ 2.5 times upper limit of normal
- Creatinine normal OR creatinine clearance ≥ 60 mL/min
- Baseline QTcF ≤ 470 msec
- No history of allergic reactions attributed to compounds of similar chemical or biologic composition to gamma secretase inhibitor RO4929097 or other agents used in the study
- No malabsorption syndrome or other condition that would interfere with intestinal absorption
- Able to swallow tablets
- Not serologically positive for hepatitis A, B, or C, or have a history of liver disease, other forms of hepatitis, or cirrhosis
- No uncontrolled electrolyte abnormalities including hypocalcemia, hypomagnesemia, hyponatremia, hypophosphatemia, or hypokalemia despite adequate electrolyte supplementation
- No uncontrolled intercurrent illness including, but not limited to, any of the following:
- Ongoing or active infection
- Symptomatic congestive heart failure
- Unstable angina pectoris
- History of torsades de pointes or other significant cardiac arrhythmia other than chronic, stable atrial fibrillation
- Psychiatric illness and/or social situations that would limit compliance with study requirements
- Recovered to < grade 2 CTCAE toxicities related to prior therapy
- No prior chemotherapy, hormonal therapy, radiotherapy, or biological therapy for breast cancer
- Prior treatment for non-melanoma skin cancer or carcinoma in situ of the cervix allowed
- No prior hormone therapy for ductal carcinoma in situ (DCIS)
- No other concurrent investigational agents
- No concurrent medications with narrow therapeutic indices that are metabolized by cytochrome P450 (CYP450), including warfarin sodium (Coumadin®)
- No concurrent medications that are strong inducers and/or inhibitors or substrates of CYP3A4
- Switching to alternative medications allowed
- No concurrent combination antiretroviral therapy for HIV-positive patients
- No concurrent antiarrhythmics or other medications known to prolong QTc
- No other concurrent anticancer agents or therapies
- No concurrent grapefruit juice
Who cannot join
None listed.
Trial locations and contacts
3 sites in 1 country.
United States3 sites
University of Alabama at Birmingham
Birmingham, Alabama, 35294
Magee-Womens Hospital of UPMC
Pittsburgh, Pennsylvania, 15213
University of Pittsburgh Cancer Institute
Pittsburgh, Pennsylvania, 15232
About this study
Official title: A Phase Ib Neoadjuvant Study of the Gamma Secretase Inhibitor (RO4929097) in Combination With the Aromatase Inhibitor Letrozole in Post-Menopausal Women With Stage II/III Hormone Receptor-Positive Breast Cancer
This phase I trial is studying the side effects and best dose of RO4929097 when given together with letrozole in treating post-menopausal women with stage II or stage III breast cancer. RO4929097 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Estrogen can cause the growth of breast cancer cells. Hormone therapy using letrozole may fight breast cancer by blocking the use of estrogen by the tumor cells. Giving RO4929097 together with letrozole may be an effective treatment for breast cancer.
Read the detailed description
PRIMARY OBJECTIVES:
- To establish the maximum-tolerated dose and the recommended phase II dose of gamma-secretase inhibitor RO4929097 (RO4929097) in combination with letrozole in post-menopausal women with hormone receptor-positive stage II or III breast cancer.
II. To assess the safety of this regimen in these patients.
SECONDARY OBJECTIVES:
- To evaluate the pharmacokinetics of this regimen, taking into consideration the induction of CYP3A4, in these patients.
II. To characterize the pharmacodynamic effects of letrozole prior to and during administration of RO4929097 with attention to suppression of estradiol and estrone levels.
III. To describe the pharmacodynamic effects of letrozole with or without RO4929097 on the NOTCH pathway, proliferation, angiogenesis, stromal cell infiltration/pathways, and comprehensive genomic analysis in tumor tissue of these patients.
IV. To describe the response, including clinical complete or partial objective response, pathological complete response, and attainment of pathologic stage 0 or I status in these patients.
OUTLINE: This is a multicenter, dose-escalation study of gamma-secretase inhibitor RO4929097(RO4929097).
Patients receive oral letrozole once daily on days 1-21. Beginning in course 2, patients also receive oral RO4929097 on days 1-3, 8-10, and 15-18. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity.
Beginning 1 week after completion of neoadjuvant therapy, patients undergo surgery or tumor biopsy. Patients continue to receive oral letrozole once daily during surgery and for an additional 4 weeks.
Blood and tumor tissue samples are collected at baseline and periodically during study for pharmacokinetics, pharmacodynamics, and correlative studies.
After completion of study therapy, patients are followed up for 1 month and then every 6 months for 5 years.
- Conditions
- Estrogen Receptor-positive Breast Cancer, HER2-negative Breast Cancer, Progesterone Receptor-positive Breast Cancer, Stage II Breast Cancer, Stage IIIA Breast Cancer
- Being tested
- letrozole, gamma-secretase/Notch signalling pathway inhibitor RO4929097, therapeutic conventional surgery, breast biopsy, diagnostic laboratory biomarker analysis
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
letrozoleDrug
Also called CGS 20267, Femara, LTZ
gamma-secretase/Notch signalling pathway inhibitor RO4929097Drug
Also called R4733, RO4929097
therapeutic conventional surgeryProcedure or surgery
breast biopsyProcedure or surgery
Also called biopsy of breast
diagnostic laboratory biomarker analysisOther
Also called pharmacological studies
| Study group | Role | What they receive |
|---|---|---|
| Arm I | Experimental | Patients receive oral letrozole once daily on days 1-21. Beginning in course 2, patients also receive oral RO4929097 on days 1-3, 8-10, and 15-18. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity.
Beginning 1 week after completion of neoadjuvant therapy, patients undergo surgery or tumor biopsy. Patients continue to receive oral letrozole once daily during surgery and for an additional 4 weeks. Receives: Drug: letrozole; Drug: gamma-secretase/Notch signalling pathway inhibitor RO4929097; Procedure: therapeutic conventional surgery; Procedure: breast biopsy; Other: diagnostic laboratory biomarker analysis; Other: pharmacological study |
What is being measured
The primary outcome is the main question the study is designed to answer.
MTD defined as the dose level at which no more than 1 of 6 patients experience a DLT, and the dose below that at which at least 2/6 patients have DLT according to NCI CTCAE version 4.0
Measured: 21 days
Secondary outcomes (20)
Measurement of NOTCH 1 and 4, activated NOTCH (ICN), Hey 1 and NOTCH ligands (DLL4 and Jagged 1)
All measurements are continuous. Descriptive statistics will be calculated to summarize change of each measurement from the baseline value. A two-sided Wilcoxon signed rank test will be used to compare each measurement at a specific time to the baseline value.
Measured: Baseline
Measurement of NOTCH 1 and 4, activated NOTCH (ICN), Hey 1 and NOTCH ligands (DLL4 and Jagged 1)
All measurements are continuous. Descriptive statistics will be calculated to summarize change of each measurement from the baseline value. A two-sided Wilcoxon signed rank test will be used to compare each measurement at a specific time to the baseline value.
Measured: 21 days
Measurement of NOTCH 1 and 4, activated NOTCH (ICN), Hey 1 and NOTCH ligands (DLL4 and Jagged 1)
All measurements are continuous. Descriptive statistics will be calculated to summarize change of each measurement from the baseline value. A two-sided Wilcoxon signed rank test will be used to compare each measurement at a specific time to the baseline value.
Measured: 42 days
Measurement of NOTCH 1 and 4, activated NOTCH (ICN), Hey 1 and NOTCH ligands (DLL4 and Jagged 1)
All measurements are continuous. Descriptive statistics will be calculated to summarize change of each measurement from the baseline value. A two-sided Wilcoxon signed rank test will be used to compare each measurement at a specific time to the baseline value.
Measured: At time of surgery
Genomic analysis of RNA transcriptome, mirco-RNA transcriptome, and DNA methylation
All measurements are continuous. Descriptive statistics will be calculated to summarize change of each measurement from the baseline value. A two-sided Wilcoxon signed rank test will be used to compare each measurement at a specific time to the baseline value. For the analysis of the gene expression data, the overall false discovery rate (FDR), which is defined as the expected portion of false positives, will be controlled at 20% to generate a list of genes for further investigation.
Measured: Baseline
Genomic analysis of RNA transcriptome, mirco-RNA transcriptome, and DNA methylation
All measurements are continuous. Descriptive statistics will be calculated to summarize change of each measurement from the baseline value. A two-sided Wilcoxon signed rank test will be used to compare each measurement at a specific time to the baseline value. For the analysis of the gene expression data, the overall FDR, which is defined as the expected portion of false positives, will be controlled at 20% to generate a list of genes for further investigation.
Measured: 21 days
Genomic analysis of RNA transcriptome, mirco-RNA transcriptome, and DNA methylation
All measurements are continuous. Descriptive statistics will be calculated to summarize change of each measurement from the baseline value. A two-sided Wilcoxon signed rank test will be used to compare each measurement at a specific time to the baseline value. For the analysis of the gene expression data, the overall FDR, which is defined as the expected portion of false positives, will be controlled at 20% to generate a list of genes for further investigation.
Measured: 42 days
Genomic analysis of RNA transcriptome, mirco-RNA transcriptome, and DNA methylation
All measurements are continuous. Descriptive statistics will be calculated to summarize change of each measurement from the baseline value. A two-sided Wilcoxon signed rank test will be used to compare each measurement at a specific time to the baseline value. For the analysis of the gene expression data, the overall FDR, which is defined as the expected portion of false positives, will be controlled at 20% to generate a list of genes for further investigation.
Measured: At time of surgery
Measurement of cell proliferation (Ki-67)
All measurements are continuous. Descriptive statistics will be calculated to summarize change of each measurement from the baseline value. A two-sided Wilcoxon signed rank test will be used to compare each measurement at a specific time to the baseline value.
Measured: Baseline
Measurement of cell proliferation (Ki-67)
All measurements are continuous. Descriptive statistics will be calculated to summarize change of each measurement from the baseline value. A two-sided Wilcoxon signed rank test will be used to compare each measurement at a specific time to the baseline value.
Measured: 21 days
Measurement of cell proliferation (Ki-67)
All measurements are continuous. Descriptive statistics will be calculated to summarize change of each measurement from the baseline value. A two-sided Wilcoxon signed rank test will be used to compare each measurement at a specific time to the baseline value.
Measured: 42 days
Measurement of cell proliferation (Ki-67)
All measurements are continuous. Descriptive statistics will be calculated to summarize change of each measurement from the baseline value. A two-sided Wilcoxon signed rank test will be used to compare each measurement at a specific time to the baseline value.
Measured: At time of surgery
Measurement of appoptosis (TUNEL and activated caspase)
All measurements are continuous. Descriptive statistics will be calculated to summarize change of each measurement from the baseline value. A two-sided Wilcoxon signed rank test will be used to compare each measurement at a specific time to the baseline value.
Measured: Baseline
Measurement of appoptosis (TUNEL and activated caspase)
All measurements are continuous. Descriptive statistics will be calculated to summarize change of each measurement from the baseline value. A two-sided Wilcoxon signed rank test will be used to compare each measurement at a specific time to the baseline value.
Measured: 21 days
Measurement of appoptosis (TUNEL and activated caspase)
All measurements are continuous. Descriptive statistics will be calculated to summarize change of each measurement from the baseline value. A two-sided Wilcoxon signed rank test will be used to compare each measurement at a specific time to the baseline value.
Measured: 42 days
Measurement of appoptosis (TUNEL and activated caspase)
All measurements are continuous. Descriptive statistics will be calculated to summarize change of each measurement from the baseline value. A two-sided Wilcoxon signed rank test will be used to compare each measurement at a specific time to the baseline value.
Measured: At time of surgery
Measurement of angiogenesis (VEGF and CD31)
All measurements are continuous. Descriptive statistics will be calculated to summarize change of each measurement from the baseline value. A two-sided Wilcoxon signed rank test will be used to compare each measurement at a specific time to the baseline value.
Measured: Baseline
Measurement of angiogenesis (VEGF and CD31)
All measurements are continuous. Descriptive statistics will be calculated to summarize change of each measurement from the baseline value. A two-sided Wilcoxon signed rank test will be used to compare each measurement at a specific time to the baseline value.
Measured: 21 days
Measurement of angiogenesis (VEGF and CD31)
All measurements are continuous. Descriptive statistics will be calculated to summarize change of each measurement from the baseline value. A two-sided Wilcoxon signed rank test will be used to compare each measurement at a specific time to the baseline value.
Measured: 42 days
Measurement of angiogenesis (VEGF and CD31)
All measurements are continuous. Descriptive statistics will be calculated to summarize change of each measurement from the baseline value. A two-sided Wilcoxon signed rank test will be used to compare each measurement at a specific time to the baseline value.
Measured: At time of surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Sep 2010 (estimated)
- Study startNov 2010
- Primary completionDec 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Estrogen Receptor-positive Breast CancerStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 28 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Shannon Puhalla, Principal investigator, University of Pittsburgh
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01208441
- Sponsor's protocol ID
- NCI-2011-02487
- Other IDs
- NCI-2011-02487, UPCI-09-080, CDR0000683397, UPCI 09-080, 8554, U01CA099168
- Status last verified
- Sep 2013
- First submitted
- 23 Sep 2010
- Last updated
- 30 Sep 2013
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 30 Sep 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase Ib Neoadjuvant Study of the Gamma Secretase Inhibitor (RO4929097) in Combination With the Aromatase Inhibitor Letrozole in Post-Menopausal Women With Stage II/III Hormone Receptor-Positive Breast Cancer
- ClinicalTrials.gov ID
- NCT01208441
- Acronym / sponsor ID
- NCI-2011-02487
- Conditions
- Estrogen Receptor-positive Breast Cancer, HER2-negative Breast Cancer, Progesterone Receptor-positive Breast Cancer, Stage II Breast Cancer, Stage IIIA Breast Cancer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Terminated
- Enrolment
- 28 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- Nov 2010
- Primary completion
- Dec 2011 (actual)
- First posted
- 24 Sep 2010 (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.
This phase I trial is studying the side effects and best dose of RO4929097 when given together with letrozole in treating post-menopausal women with stage II or stage III breast cancer. RO4929097 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Estrogen can cause the growth of breast cancer cells. Hormone therapy using letrozole may fight breast cancer by blocking the use of estrogen by the tumor cells. Giving RO4929097 together with letrozole may be an effective treatment for breast cancer.
Detailed description
PRIMARY OBJECTIVES:
- To establish the maximum-tolerated dose and the recommended phase II dose of gamma-secretase inhibitor RO4929097 (RO4929097) in combination with letrozole in post-menopausal women with hormone receptor-positive stage II or III breast cancer.
II. To assess the safety of this regimen in these patients.
SECONDARY OBJECTIVES:
- To evaluate the pharmacokinetics of this regimen, taking into consideration the induction of CYP3A4, in these patients.
II. To characterize the pharmacodynamic effects of letrozole prior to and during administration of RO4929097 with attention to suppression of estradiol and estrone levels.
III. To describe the pharmacodynamic effects of letrozole with or without RO4929097 on the NOTCH pathway, proliferation, angiogenesis, stromal cell infiltration/pathways, and comprehensive genomic analysis in tumor tissue of these patients.
IV. To describe the response, including clinical complete or partial objective response, pathological complete response, and attainment of pathologic stage 0 or I status in these patients.
OUTLINE: This is a multicenter, dose-escalation study of gamma-secretase inhibitor RO4929097(RO4929097).
Patients receive oral letrozole once daily on days 1-21. Beginning in course 2, patients also receive oral RO4929097 on days 1-3, 8-10, and 15-18. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity.
Beginning 1 week after completion of neoadjuvant therapy, patients undergo surgery or tumor biopsy. Patients continue to receive oral letrozole once daily during surgery and for an additional 4 weeks.
Blood and tumor tissue samples are collected at baseline and periodically during study for pharmacokinetics, pharmacodynamics, and correlative studies.
After completion of study therapy, patients are followed up for 1 month and then every 6 months for 5 years.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Arm I | Experimental | Drug: letrozole, Drug: gamma-secretase/Notch signalling pathway inhibitor RO4929097, Procedure: therapeutic conventional surgery, Procedure: breast biopsy, Other: diagnostic laboratory biomarker analysis, Other: pharmacological studyPatients receive oral letrozole once daily on days 1-21. Beginning in course 2, patients also receive oral RO4929097 on days 1-3, 8-10, and 15-18. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Beginning 1 week after completion of neoadjuvant therapy, patients undergo surgery or tumor biopsy. Patients continue to receive oral letrozole once daily during surgery and for an additional 4 weeks. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (47 listed)
- Pathologically confirmed invasive breast cancer
- Bilateral disease allowed as long as all tumors are ER+ and ≥ 1 is T2-T3
- Patient must have disease that is palpable on physical exam and able to be imaged via breast ultrasound
- No metastatic disease by CT scans of the chest, abdomen, and pelvis, a PET/CT bone scan, or nuclear medicine bone scan
- No inflammatory breast cancer or presence of breast tumor cells in the dermal lymphatics of the breast
Key exclusion criteria (0 listed)
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 |
|---|---|---|
| letrozoleAlso: CGS 20267, Femara, LTZ | Drug | Arm I |
| gamma-secretase/Notch signalling pathway inhibitor RO4929097Also: R4733, RO4929097 | Drug | Arm I |
| therapeutic conventional surgery | Procedure or surgery | Arm I |
| breast biopsyAlso: biopsy of breast | Procedure or surgery | Arm I |
| diagnostic laboratory biomarker analysis | Other | Arm I |
| pharmacological studyAlso: pharmacological studies | Other | Arm I |
Primary outcome
MTD defined as the dose level at which no more than 1 of 6 patients experience a DLT, and the dose below that at which at least 2/6 patients have DLT according to NCI CTCAE version 4.0
Time frame: 21 days
20 secondary outcomes
Measurement of NOTCH 1 and 4, activated NOTCH (ICN), Hey 1 and NOTCH ligands (DLL4 and Jagged 1)
Time frame: Baseline
Measurement of NOTCH 1 and 4, activated NOTCH (ICN), Hey 1 and NOTCH ligands (DLL4 and Jagged 1)
Time frame: 21 days
Measurement of NOTCH 1 and 4, activated NOTCH (ICN), Hey 1 and NOTCH ligands (DLL4 and Jagged 1)
Time frame: 42 days
Measurement of NOTCH 1 and 4, activated NOTCH (ICN), Hey 1 and NOTCH ligands (DLL4 and Jagged 1)
Time frame: At time of surgery
Genomic analysis of RNA transcriptome, mirco-RNA transcriptome, and DNA methylation
Time frame: Baseline
Genomic analysis of RNA transcriptome, mirco-RNA transcriptome, and DNA methylation
Time frame: 21 days
Genomic analysis of RNA transcriptome, mirco-RNA transcriptome, and DNA methylation
Time frame: 42 days
Genomic analysis of RNA transcriptome, mirco-RNA transcriptome, and DNA methylation
Time frame: At time of surgery
Measurement of cell proliferation (Ki-67)
Time frame: Baseline
Measurement of cell proliferation (Ki-67)
Time frame: 21 days
Measurement of cell proliferation (Ki-67)
Time frame: 42 days
Measurement of cell proliferation (Ki-67)
Time frame: At time of surgery
Measurement of appoptosis (TUNEL and activated caspase)
Time frame: Baseline
Measurement of appoptosis (TUNEL and activated caspase)
Time frame: 21 days
Measurement of appoptosis (TUNEL and activated caspase)
Time frame: 42 days
Measurement of appoptosis (TUNEL and activated caspase)
Time frame: At time of surgery
Measurement of angiogenesis (VEGF and CD31)
Time frame: Baseline
Measurement of angiogenesis (VEGF and CD31)
Time frame: 21 days
Measurement of angiogenesis (VEGF and CD31)
Time frame: 42 days
Measurement of angiogenesis (VEGF and CD31)
Time frame: At time of surgery
Results and safety
The study was stopped early. Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Sep 2013.
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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.
Shannon Puhalla principal investigator
University of Pittsburgh
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing letrozole, gamma-secretase/Notch signalling pathway inhibitor RO4929097 and therapeutic conventional surgery in people with Estrogen Receptor-positive Breast Cancer and HER2-negative Breast Cancer, run by National Cancer Institute (NCI) 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 47 inclusion and 0 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: stopped early, as of the sponsor's last update on 30 Sep 2013. 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 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 was stopped early. Results are not available in the source record.
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?
MTD defined as the dose level at which no more than 1 of 6 patients experience a DLT, and the dose below that at which at least 2/6 patients have DLT according to NCI CTCAE version 4.0 (time frame: 21 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 Sep 2013.