Estrogen Receptor NegativePhase 2NCT01319539
MK2206 in Treating Patients With Stage I, Stage II, or Stage III Breast Cancer
A Phase 2 study testing Akt Inhibitor MK2206, Therapeutic Conventional Surgery and Pharmacological Study in people with Estrogen Receptor Negative and Estrogen Receptor Positive, run by National Cancer Institute (NCI) at 3 sites in United States.
Trial summary
This phase II trial is studies how well Akt inhibitor MK2206 works in treating patients with stage I-III breast cancer that can be removed by surgery. Akt inhibitor MK2206 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 Negative, Estrogen Receptor Positive, HER2/Neu Negative
- What is being tested?
- Akt Inhibitor MK2206, Therapeutic Conventional Surgery and Pharmacological Study
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 3 sitesUnited States
- Study dates
- Apr 2011to Jul 2013
- Phase
- Phase 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
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients must have histologically-confirmed operable invasive breast cancer and have undergone core needle biopsy with an anticipated surgical resection for residual disease after enrollment
- Patients must have clinical stage I-III invasive breast (invasive tumor must be clinically at least >= T1c by radiograph or palpation)
- Patients must have available tissue from core biopsies for biomarker assessment; it is recommended that at least 4 cores be performed with 12 gauge (or smaller gauge) needles; this includes cores underneath ultrasound-guidance
- Patients are planning to undergo surgical treatment with either segmental resection or total mastectomy (required: 2 doses of weekly MK-2206 prior to surgery; the first dose will be at day -9 [+/- 1 day] and second dose at day -2 [+/- 1 day] in relation to surgery [day 0])
- Patients may have a history of contralateral breast cancer, provided there is no evidence of recurrence of the initial primary breast cancer
- Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 (Karnofsky >= 80%)
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- Leukocytes >= 3,000/ul within 28 days of registration
- Platelets >= 100,000 /uL within 28 days of registration
- Hemoglobin (Hgb) >= 9 g/dL within 28 days of registration
- Creatinine =< 1.5 x upper limit of normal (ULN) within 28 days of registration
- Prothrombin time (PT), partial thromboplastin time (PTT) =< 1.2 x ULN within 28 days of registration
- Total bilirubin =< 1.5 x ULN within 28 days of registration
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 2.5 x ULN within 28 days of registration
- Patients of childbearing potential must have a negative serum or urine pregnancy test beta-human chorionic gonadotropin (β-hCG) within 72 hours prior to receiving the first dose of study medication
- Women of childbearing potential and men must use two forms of contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, the patient should inform the treating physician immediately
- Patient must be able to swallow oral tablets
- Ability to understand and the willingness to sign a written informed consent document
- Patients must agree to biomarker assessment of pre-treatment diagnostic core biopsy tissue and the surgical resection tissue (i.e. excision or mastectomy); also, must agree to pre- and post-treatment fasting blood biomarker collection
Who cannot join
- Patients may not have any known evidence of distant metastatic disease (i.e., lung, liver, bone, or brain metastases) or locally recurrent breast cancer
- Patients with inflammatory breast cancer are not eligible
- Patients with prior chemotherapy or radiation therapy within 6 months of study entry are not eligible (i.e. patient who have received neoadjuvant therapy are not eligible)
- Patients may not be receiving any other investigational agents, including other inhibitors of PI3K, Akt, or mammalian target of rapamycin (mTOR)
- Men diagnosed with breast cancer
- Patients may not have a history of allergic reactions attributed to compounds of similar chemical or biologic composition to MK-2206 used in the study
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- Patients with known diabetes which is poorly controlled diabetes (hemoglobin A1c [HBA1C] >= 8%) should be excluded; if patient is taking metformin, must have been taking this medication for > 3 months, as metformin is thought to impact PI3K/Akt signaling
- Baseline corrected QT interval (QTc) > 470 msec will exclude patients from entry on study; patients with a baseline bundle branch block will be excluded
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
- Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with MK2206
- Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Columbia University Medical Center
New York, New York, 10032
Albert Einstein College of Medicine
The Bronx, New York, 10461
Montefiore Medical Center - Moses Campus
The Bronx, New York, 10467-2490
About this study
Official title: Pre-surgical Evaluation of MK-2206 in Patients With Operable Invasive Breast Cancer
This phase II trial is studies how well Akt inhibitor MK2206 works in treating patients with stage I-III breast cancer that can be removed by surgery. Akt inhibitor MK2206 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
Read the detailed description
PRIMARY OBJECTIVES:
- To assess for a decrease in phosphorylated (phospho)-protein kinase B (Akt) (Ser^473) levels in tissue after a pre-surgical trial of weekly MK2206 (Akt inhibitor MK2206) (2 doses) in patients with operable invasive breast cancer.
SECONDARY OBJECTIVES:
- To evaluate the effects of MK2206 on the immunohistochemical expression of other phosphatidylinositide 3-kinase (PI3K)/AKT pathway biomarkers on pre-and post-MK2206 tumor tissue, such as phospho-S6 kinase.
II. To assess modulation of PI3K/AKT signaling following MK2206 use with reverse-phase protein microarray analysis.
III. To explore whether phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (PIK3CA) mutations demonstrate different modulation of PI3K/Akt-pathway signaling as compared to tumors with loss of phosphatase and tensin homolog (PTEN).
IV. To explore whether MK2206 alters PI3K/Akt pathway signaling differently in hormone receptor-positive/human epidermal growth factor receptor (HER)2-negative tumors, as compared to triple-negative or HER2-positive breast cancers.
- To evaluate whether tumor proliferation, as measured by Ki-67 staining of breast tumor cells, is reduced in patients taking MK2206 pre-surgically and correlate Ki-67 modulation with changes in PI3K/AKT signaling.
VI. To determine safety and tolerability of MK2206 in patients with early-stage breast cancer.
VII. To collect fasting blood for evaluation of predictive markers of drug effect, such as markers in the insulin growth-factor receptor pathway (i.e., fasting insulin, c-peptide, insulin-like growth factor [IGF]-1, and IGF binding protein [BP]-1 and 3), as well as modulation of phospho-markers in peripheral blood mononuclear cells.
OUTLINE:
Patients receive Akt inhibitor MK2206 orally (PO) on days -9 and -2, and undergo segmental resection or total mastectomy on day 0.
After completion of study treatment, patients are followed up for 4 weeks.
- Conditions
- Estrogen Receptor Negative, Estrogen Receptor Positive, HER2/Neu Negative, HER2/Neu Positive, Progesterone Receptor Negative, Progesterone Receptor Positive
- Being tested
- Akt Inhibitor MK2206, Therapeutic Conventional Surgery, Pharmacological Study, Laboratory Biomarker Analysis
- Medical subject headings
- Breast Neoplasms, Triple Negative Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Akt Inhibitor MK2206Drug
Also called MK2206
Given PO
Therapeutic Conventional SurgeryProcedure or surgery
Undergo surgery
Also called pharmacological studies
Correlative studies
Laboratory Biomarker AnalysisOther
Correlative studies
| Study group | Role | What they receive |
|---|---|---|
| Treatment (Akt inhibitor MK2206) | Experimental | Patients receive Akt inhibitor MK2206 PO on days -9 and -2, and undergo segmental resection or total mastectomy (therapeutic conventional surgery) on day 0. Patient samples will be processed for pharmacological study and laboratory biomarker analysis. Receives: Drug: Akt Inhibitor MK2206; Procedure: Therapeutic Conventional Surgery; Other: Pharmacological Study; Other: Laboratory Biomarker Analysis |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in pAKT Levels
This is designed to evaluate response to therapy - comparing changes within group (example: invasive pre-MK-2206-treated core versus post-MK-2206-treated surgical tissue).
Measured: Baseline, 2 weeks (Day 0 - surgery)
Secondary outcomes (2)
Change in pS6 Levels
This is designed to evaluate response to therapy - comparing changes within group (example: invasive pre-MK-2206-treated core versus post-MK-2206-treated surgical tissue).
Measured: Baseline, 2 weeks (Day 0 - surgery)
Change in Ki-67 Expression
This is designed to evaluate response to therapy - comparing changes within group (example: invasive pre-MK-2206-treated core versus post-MK-2206-treated surgical tissue).
Measured: Baseline, 2 weeks (Day 0 - surgery)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Mar 2011 (estimated)
- Study startApr 2011
- Primary completionJul 2013
- Study completionJul 2013
Why it stopped: terminated early, due to toxicity
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.
- Other trials for Estrogen Receptor NegativeStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Kevin Kalinsky, Principal investigator, Montefiore Medical Center - Moses Campus
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01319539
- Sponsor's protocol ID
- NCI-2011-02513
- Other IDs
- NCI-2011-02513, CDR0000696821, AECM-AAAF3912, 8740, N01CM62204, P30CA013330
- Status last verified
- Aug 2017
- First submitted
- 18 Mar 2011
- Last updated
- 30 Aug 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 30 Aug 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pre-surgical Evaluation of MK-2206 in Patients With Operable Invasive Breast Cancer
- ClinicalTrials.gov ID
- NCT01319539
- Acronym / sponsor ID
- NCI-2011-02513
- Conditions
- Estrogen Receptor Negative, Estrogen Receptor Positive, HER2/Neu Negative, HER2/Neu Positive, Progesterone Receptor Negative, Progesterone Receptor Positive
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: terminated early, due to toxicity
- Enrolment
- 12 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- Apr 2011
- Primary completion
- Jul 2013 (actual)
- Study completion
- Jul 2013 (actual)
- First posted
- 21 Mar 2011 (estimated)
- Results
- Posted 1 Aug 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This phase II trial is studies how well Akt inhibitor MK2206 works in treating patients with stage I-III breast cancer that can be removed by surgery. Akt inhibitor MK2206 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
Detailed description
PRIMARY OBJECTIVES:
- To assess for a decrease in phosphorylated (phospho)-protein kinase B (Akt) (Ser^473) levels in tissue after a pre-surgical trial of weekly MK2206 (Akt inhibitor MK2206) (2 doses) in patients with operable invasive breast cancer.
SECONDARY OBJECTIVES:
- To evaluate the effects of MK2206 on the immunohistochemical expression of other phosphatidylinositide 3-kinase (PI3K)/AKT pathway biomarkers on pre-and post-MK2206 tumor tissue, such as phospho-S6 kinase.
II. To assess modulation of PI3K/AKT signaling following MK2206 use with reverse-phase protein microarray analysis.
III. To explore whether phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (PIK3CA) mutations demonstrate different modulation of PI3K/Akt-pathway signaling as compared to tumors with loss of phosphatase and tensin homolog (PTEN).
IV. To explore whether MK2206 alters PI3K/Akt pathway signaling differently in hormone receptor-positive/human epidermal growth factor receptor (HER)2-negative tumors, as compared to triple-negative or HER2-positive breast cancers.
- To evaluate whether tumor proliferation, as measured by Ki-67 staining of breast tumor cells, is reduced in patients taking MK2206 pre-surgically and correlate Ki-67 modulation with changes in PI3K/AKT signaling.
VI. To determine safety and tolerability of MK2206 in patients with early-stage breast cancer.
VII. To collect fasting blood for evaluation of predictive markers of drug effect, such as markers in the insulin growth-factor receptor pathway (i.e., fasting insulin, c-peptide, insulin-like growth factor [IGF]-1, and IGF binding protein [BP]-1 and 3), as well as modulation of phospho-markers in peripheral blood mononuclear cells.
OUTLINE:
Patients receive Akt inhibitor MK2206 orally (PO) on days -9 and -2, and undergo segmental resection or total mastectomy on day 0.
After completion of study treatment, patients are followed up for 4 weeks.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (Akt inhibitor MK2206) | Experimental | Drug: Akt Inhibitor MK2206, Procedure: Therapeutic Conventional Surgery, Other: Pharmacological Study, Other: Laboratory Biomarker AnalysisPatients receive Akt inhibitor MK2206 PO on days -9 and -2, and undergo segmental resection or total mastectomy (therapeutic conventional surgery) on day 0. Patient samples will be processed for pharmacological study and laboratory biomarker analysis. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- Patients must have histologically-confirmed operable invasive breast cancer and have undergone core needle biopsy with an anticipated surgical resection for residual disease after enrollment
- Patients must have clinical stage I-III invasive breast (invasive tumor must be clinically at least >= T1c by radiograph or palpation)
- Patients must have available tissue from core biopsies for biomarker assessment; it is recommended that at least 4 cores be performed with 12 gauge (or smaller gauge) needles; this includes cores underneath ultrasound-guidance
- Patients are planning to undergo surgical treatment with either segmental resection or total mastectomy (required: 2 doses of weekly MK-2206 prior to surgery; the first dose will be at day -9 [+/- 1 day] and second dose at day -2 [+/- 1 day] in relation to surgery [day 0])
- Patients may have a history of contralateral breast cancer, provided there is no evidence of recurrence of the initial primary breast cancer
Key exclusion criteria (11 listed)
- Patients may not have any known evidence of distant metastatic disease (i.e., lung, liver, bone, or brain metastases) or locally recurrent breast cancer
- Patients with inflammatory breast cancer are not eligible
- Patients with prior chemotherapy or radiation therapy within 6 months of study entry are not eligible (i.e. patient who have received neoadjuvant therapy are not eligible)
- Patients may not be receiving any other investigational agents, including other inhibitors of PI3K, Akt, or mammalian target of rapamycin (mTOR)
- Men diagnosed with breast cancer
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 |
|---|---|---|
| Akt Inhibitor MK2206Also: MK2206Given PO | Drug | Treatment (Akt inhibitor MK2206) |
| Therapeutic Conventional SurgeryUndergo surgery | Procedure or surgery | Treatment (Akt inhibitor MK2206) |
| Pharmacological StudyAlso: pharmacological studiesCorrelative studies | Other | Treatment (Akt inhibitor MK2206) |
| Laboratory Biomarker AnalysisCorrelative studies | Other | Treatment (Akt inhibitor MK2206) |
Primary outcome
Change in pAKT Levels
Time frame: Baseline, 2 weeks (Day 0 - surgery)
This is designed to evaluate response to therapy - comparing changes within group (example: invasive pre-MK-2206-treated core versus post-MK-2206-treated surgical tissue).
2 secondary outcomes
Change in pS6 Levels
Time frame: Baseline, 2 weeks (Day 0 - surgery)
Change in Ki-67 Expression
Time frame: Baseline, 2 weeks (Day 0 - surgery)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Aug 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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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.
Kevin Kalinsky principal investigator
Montefiore Medical Center - Moses Campus
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Akt Inhibitor MK2206, Therapeutic Conventional Surgery and Pharmacological Study in people with Estrogen Receptor Negative and Estrogen Receptor Positive, 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 18 inclusion and 11 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 Aug 2017. 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 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 1 Aug 2017). 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?
Change in pAKT Levels (time frame: Baseline, 2 weeks (Day 0 - surgery)). 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 Aug 2017.