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MK2206 in Treating Patients With Stage I, Stage II, or Stage III Breast Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01319539
Recruitment Status : Terminated (terminated early, due to toxicity)
First Posted : March 21, 2011
Results First Posted : August 1, 2017
Last Update Posted : August 30, 2017
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Tracking Information
First Submitted Date  ICMJE March 18, 2011
First Posted Date  ICMJE March 21, 2011
Results First Submitted Date  ICMJE October 14, 2016
Results First Posted Date  ICMJE August 1, 2017
Last Update Posted Date August 30, 2017
Study Start Date  ICMJE April 2011
Actual Primary Completion Date July 2013   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 5, 2017)
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).
Original Primary Outcome Measures  ICMJE
 (submitted: March 18, 2011)
Decrease in phospho-Akt (Ser473) levels in tissue after a pre-surgical intervention of MK2206
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 5, 2017)
  • Change in pS6 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).
  • Change in Ki-67 Expression [ 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).
Original Secondary Outcome Measures  ICMJE
 (submitted: March 18, 2011)
  • Relationship between MK2206 treatment and PI3K/AKT expression
  • Relationship between MK2206 and Ki-67 reduction
  • Safety and tolerability of MK2206 in patients with early-stage breast cancer
  • MK2206 effects on insulin growth-factor receptor pathway (i.e., fasting insulin, c-peptide, IGF-1, and IGFBP-1 and 3), as well as modulation of phospho-markers in peripheral blood mononuclear cells
  • Toxicity of MK2206
  • Biologic response to MK2206
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE MK2206 in Treating Patients With Stage I, Stage II, or Stage III Breast Cancer
Official Title  ICMJE Pre-surgical Evaluation of MK-2206 in Patients With Operable Invasive Breast Cancer
Brief 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.
Detailed Description

PRIMARY OBJECTIVES:

I. 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:

I. 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.

V. 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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Estrogen Receptor Negative
  • Estrogen Receptor Positive
  • HER2/Neu Negative
  • HER2/Neu Positive
  • Progesterone Receptor Negative
  • Progesterone Receptor Positive
  • Stage IA Breast Cancer
  • Stage IB Breast Cancer
  • Stage IIA Breast Cancer
  • Stage IIB Breast Cancer
  • Stage IIIA Breast Cancer
  • Stage IIIB Breast Cancer
  • Stage IIIC Breast Cancer
  • Triple-Negative Breast Carcinoma
Intervention  ICMJE
  • Drug: Akt Inhibitor MK2206
    Given PO
    Other Name: MK2206
  • Procedure: Therapeutic Conventional Surgery
    Undergo surgery
  • Other: Pharmacological Study
    Correlative studies
    Other Name: pharmacological studies
  • Other: Laboratory Biomarker Analysis
    Correlative studies
Study Arms  ICMJE Experimental: Treatment (Akt inhibitor MK2206)
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.
Interventions:
  • Drug: Akt Inhibitor MK2206
  • Procedure: Therapeutic Conventional Surgery
  • Other: Pharmacological Study
  • Other: Laboratory Biomarker Analysis
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: July 5, 2017)
12
Original Estimated Enrollment  ICMJE
 (submitted: March 18, 2011)
30
Actual Study Completion Date  ICMJE July 2013
Actual Primary Completion Date July 2013   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • 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%)
  • 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

Exclusion Criteria:

  • 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
  • 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
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01319539
Other Study ID Numbers  ICMJE NCI-2011-02513
NCI-2011-02513 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
CDR0000696821 ( Other Identifier: NCI )
AECM-AAAF3912 ( Other Identifier: Montefiore Medical Center - Moses Campus )
8740 ( Other Identifier: CTEP )
N01CM62204 ( U.S. NIH Grant/Contract )
P30CA013330 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party National Cancer Institute (NCI)
Study Sponsor  ICMJE National Cancer Institute (NCI)
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Kevin Kalinsky Montefiore Medical Center - Moses Campus
PRS Account National Cancer Institute (NCI)
Verification Date August 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP