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Akt Inhibitor MK-2206 and Anastrozole With or Without Goserelin Acetate in Treating Patients With Stage II-III Breast Cancer

This study is ongoing, but not recruiting participants.
Information provided by (Responsible Party):
National Cancer Institute (NCI) Identifier:
First received: January 23, 2013
Last updated: April 24, 2017
Last verified: April 2017
This phase II trial studies how well Akt inhibitor MK-2206 (MK-2206) and anastrozole with or without goserelin acetate works in treating patients with stage II-III breast cancer. MK-2206 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 anastrozole and goserelin acetate may fight breast cancer by blocking the use of estrogen by the tumor cells. Giving MK-2206, anastrozole, and goserelin acetate together may kill more tumor cells.

Condition Intervention Phase
Estrogen Receptor Positive
HER2/Neu Negative
Recurrent Breast Carcinoma
Stage IIA Breast Cancer
Stage IIB Breast Cancer
Stage IIIA Breast Cancer
Stage IIIB Breast Cancer
Stage IIIC Breast Cancer
Drug: Akt Inhibitor MK2206
Drug: Anastrozole
Drug: Goserelin Acetate
Other: Laboratory Biomarker Analysis
Procedure: Neoadjuvant Therapy
Other: Pharmacological Study
Procedure: Therapeutic Conventional Surgery
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: No masking
Primary Purpose: Treatment
Official Title: A Phase II Trial of Neoadjuvant MK-2206 in Combination With Either Anastrozole if Postmenopausal or Anastrozole and Goserelin if Premenopausal in Women With Clinical Stage 2 or 3 PIK3CA Mutant Estrogen Receptor Positive and HER2 Negative Invasive Breast Cancer

Resource links provided by NLM:

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Pathological complete response based on tumor Ki-67 value [ Time Frame: Up to day 17 of course 1 ]
    A ninety percent confidence interval for the true pathologic complete response rate will be calculated using the Duffy-Santer approach.

Secondary Outcome Measures:
  • Clinical response rate, estimated by the number of patients whose disease meets the WHO criteria of complete or partial response divided by the total number of eligible patients [ Time Frame: Up to 3 weeks following the last dose of Akt inhibitor MK-2206 ]
    A ninety percent confidence interval for the true clinical response rate will be calculated using the Duffy-Santer approach.

  • Incidence of adverse events, based on the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 [ Time Frame: Up to 60 days after completion of study treatment ]
    The maximum grade for each type of adverse event will be recorded for each patient, and frequency tables will be reviewed to determine patterns. Additionally, the relationship of the adverse event(s) to the study treatment will be taken into consideration.

  • Radiological response rate, estimated by the number of patients whose disease meets with WHO criteria for complete or partial response divided by the total number of eligible patients [ Time Frame: Up to 3 weeks following the last dose of Akt inhibitor MK-2206 ]
    A ninety percent confidence interval for the true radiographic response rate will be calculated using the Duffy-Santer approach.

Other Outcome Measures:
  • Change in Ki67 levels [ Time Frame: From 2 weeks of combination therapy with Akt inhibitor MK2206 and anastrozole (day 17 of course 1) to after 4 weeks of treatment with anastrozole alone ]
  • Percent change in the apoptotic index [ Time Frame: From 2 weeks of combination therapy with Akt inhibitor MK2206 and anastrozole (day 17 of course 1) to after 4 weeks of treatment with anastrozole alone ]
  • Proportion of patients whose Ki67 values is at most 10% [ Time Frame: From 2 weeks of combination therapy with Akt inhibitor MK2206 and anastrozole (day 17 of course 1) to after 4 weeks of treatment with anastrozole alone ]
    A 95% binomial confidence intervals will be constructed for the true proportion of patients whose pre Akt inhibitor MK2206 ki67 value is at most 10% as well as for the true proportion of patients with a C1D17 Ki67 value that is at most 10% among those patients whose pre Akt inhibitor MK2206 Ki67 was more than 10%.

  • Serum estradiol levels [ Time Frame: At baseline, following 4 weeks of anastrozole alone, day 1 of course 3, and at pre-surgery ]
  • The pharmacodynamic effect of Akt inhibitor MK2206 in combination with anastrozole on the PI3K pathway activities, assessed by phosphoroproteomics and immunohistochemistry analysis on serial tumor biopsies [ Time Frame: Up to 3 weeks following the last dose of Akt inhibitor MK-2206 ]

Enrollment: 16
Study Start Date: January 2013
Primary Completion Date: December 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (MK2206, anastrozole, goserelin acetate)
Patients receive Akt inhibitor MK-2206 PO on days 2, 9, 16, and 23; anastrozole PO daily on days 1-28; and goserelin acetate SC on day 1 (premenopausal patients only). Treatment repeats every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity.
Drug: Akt Inhibitor MK2206
Given PO
Other Name: MK2206
Drug: Anastrozole
Given PO
Other Names:
  • Anastrazole
  • Arimidex
  • ICI D1033
  • ICI-D1033
  • ZD-1033
Drug: Goserelin Acetate
Given SC
Other Names:
  • ZDX
  • Zoladex
Other: Laboratory Biomarker Analysis
Correlative studies
Procedure: Neoadjuvant Therapy
Given before standard-care surgery
Other Names:
  • Induction Therapy
  • Neoadjuvant
  • Preoperative Therapy
Other: Pharmacological Study
Correlative studies
Procedure: Therapeutic Conventional Surgery
Undergo standard-care surgery

  Show Detailed Description


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Clinical T2-T4c, any N, M0 invasive ER+ (Allred score of 6-8) and HER2 negative (0 or 1+ by immunohistochemistry [IHC] or fluorescence in situ hybridization [FISH] negative for amplification) breast cancer, by American Joint Committee on Cancer (AJCC) 7th edition clinical staging, with the goal being surgery to completely excise the tumor in the breast and the lymph node;

    • Note: if the patient has invasive or ductal carcinoma in situ (DCIS) in the contralateral breast the patient is not eligible for this study
  • >= 1 measurable lesion that is palpable, its size can be measured by bi-dimensional tape, ruler or caliper technique, and the minimum size of the largest tumor diameter is greater than 2.0 cm by imaging or physical examination
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2
  • Life expectancy > 4 months
  • Leukocytes >= 3,000/mcL
  • Absolute neutrophil count >= 1,500/mcL
  • Platelets >= 100,000/mcL
  • Total bilirubin =< upper limit of normal (ULN)
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional ULN
  • Creatinine =< ULN OR creatinine clearance >= 60 mL/min/1.73 m^2 for patients with creatinine above institutional normal
  • Patient with diabetes mellitus: fasting glucose =< 120 mg/dL and hemoglobin A1c (HbA1c) =< 8%
  • Negative serum pregnancy test =< 7 days prior to pre-registration for women of childbearing potential
  • Ability to understand and the willingness to sign a written informed consent document
  • Patient is postmenopausal or premenopausal

    • NOTE: postmenopausal women, verified by

      • Bilateral surgical oophorectomy, or
      • No spontaneous menses >= 1 year or
      • No menses for < 1 year with follicle stimulating hormone (FSH) and estradiol levels in postmenopausal range, according to institutional standards or
    • Premenopausal women, verified by:

      • Regular menses or
      • FSH and estradiol levels in premenopausal range, according to institutional standards
  • Willingness to provide biologic samples for PIK3CA sequencing and correlative studies
  • Positive for PIK3CA mutation based on central laboratory testing
  • In premenopausal women, serum estradiol level in postmenopausal range =< 7 days prior to registration

Exclusion Criteria:

  • Any of the following for treatment of this cancer including:

    • Surgery
    • Radiation therapy
    • Chemotherapy
    • Biotherapy
    • Hormonal therapy
    • Investigational agent prior to study entry
  • Receiving any other investigational agents
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to MK-2206 or other agents used in this study
  • Prior axillary lymph node sampling (sentinel lymph node biopsy or axillary lymph node dissection); NOTE: fine needle aspiration (FNA) of axillary lymph node is acceptable
  • Invasive cancer or DCIS in the contralateral breast
  • Receiving any medications or substances that are strong inhibitors or inducers of cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP450 3A4);

    • NOTE: oxidative metabolism of MK-2206 in human liver microsomes is catalyzed primarily by CYP3A4, although direct glucuronidation also occurs; at least 7 days washout period is required in patients who were previously taking strong inhibitors or inducers of CYP.450 3A4; patients who are currently taking moderate inhibitors or inducers of CYP450 3A4 are encouraged to switch to other medications that do not interact with CYP450 3A4
  • Corrected QT interval (QTc) prolongation (defined as a QTc interval > 480 msec) or other significant electrocardiogram (ECG) abnormalities
  • Receiving any medications or substances with risk of torsades de pointes; Note: medications or substances on the list "Drugs with Risk of Torsades de Pointes" are prohibited; medications or substances on the list "Drugs with Possible or Conditional Risk of Torsades de Pointes" may be used while on study with extreme caution and careful monitoring
  • Uncontrolled intercurrent illness including, but not limited to:

    • Ongoing or active infection
    • Symptomatic congestive heart failure
    • Unstable angina pectoris
    • Uncontrolled symptomatic cardiac arrhythmia
    • Psychiatric illness/social situations that would limit compliance with study requirements
  • Any of the following:

    • Pregnant women
    • Nursing women
    • Women of childbearing potential who are unwilling to employ adequate contraception
    • NOTE: breastfeeding should be discontinued if the mother is treated with MK-2206; women of childbearing potential 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
  • Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy; NOTE: HIV-positive patients on combination antiretroviral therapy are ineligible; in addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy
  • Evidence of inflammatory cancer (clinical presentation of skin erythema involving more than one third of the breast or pathological evidence of dermal lymphatic involvement)
  • Patients with known metastatic disease are excluded
  • Current use of therapeutic anticoagulation therapy
  • Previous excisional biopsy of the breast cancer
  • Any condition (e.g., gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for intravenous [IV] alimentation, prior surgical procedures affecting absorption) that impairs patients ability to swallow MK-2206 tablets
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT01776008

United States, Arizona
Mayo Clinic in Arizona
Scottsdale, Arizona, United States, 85259
United States, Illinois
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, United States, 60637
United States, Iowa
University of Iowa/Holden Comprehensive Cancer Center
Iowa City, Iowa, United States, 52242
United States, Maryland
Johns Hopkins University/Sidney Kimmel Cancer Center
Baltimore, Maryland, United States, 21287
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
Metro Minnesota Community Oncology Research Consortium
Saint Louis Park, Minnesota, United States, 55416
United States, Missouri
Washington University School of Medicine
Saint Louis, Missouri, United States, 63110
United States, Wisconsin
University of Wisconsin Hospital and Clinics
Madison, Wisconsin, United States, 53792
Sponsors and Collaborators
National Cancer Institute (NCI)
Principal Investigator: Cynthia Ma Mayo Clinic Cancer Center P2C
  More Information

Responsible Party: National Cancer Institute (NCI) Identifier: NCT01776008     History of Changes
Other Study ID Numbers: NCI-2013-00080
NCI-2013-00080 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
MC1139 ( Other Identifier: Mayo Clinic Cancer Center P2C )
9170 ( Other Identifier: CTEP )
N01CM00071 ( US NIH Grant/Contract Award Number )
N01CM00099 ( US NIH Grant/Contract Award Number )
P30CA015083 ( US NIH Grant/Contract Award Number )
Study First Received: January 23, 2013
Last Updated: April 24, 2017

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Aromatase Inhibitors
Steroid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Estrogen Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs processed this record on April 28, 2017