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

NCT01776008 | Terminated Phase 2 Results DMC

• 6 other identifiers: NCI-2013-00080MC11399170N01CM00071N01CM00099P30CA015083
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 8

Brief Summary

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.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• Pathological Complete Response Rate

  Any woman whose Ki67 value ≤10% on cycle 1 day 17 of combination treatment who does not receive alternative treatment prior to surgery and has no histologic evidence of invasive tumor cells in the surgical breast specimen and the axillary lymph nodes is considered to have a pathological complete response (pCR). A ninety percent confidence interval for the true pathologic complete response rate will be calculated using the Duffy-Santer approach.

  At time of surgery (up to 3 weeks after 4, 28-day cycles)

Secondary Outcomes (3)

• Clinical Response Rate

  Baseline to end of Cycle 4 (28 day cycles)

• Incidence of Adverse Events, Based on the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0

  Baseline to end of Cycle 4 (28 day cycles)

• Radiological Response Rate

  Baseline and completion of cycle 4 (28 day cycles)

Other Outcomes (5)

• Change in Ki67 Levels

  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

  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%

  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

Study Arms (1)

Treatment (MK2206, anastrozole, goserelin acetate)

EXPERIMENTAL

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; Drug: Anastrozole; Drug: Goserelin Acetate; Other: Laboratory Biomarker Analysis; Procedure: Neoadjuvant Therapy; Other: Pharmacological Study; Procedure: Therapeutic Conventional Surgery

Interventions

Akt Inhibitor MK2206 DRUG

Given PO

Also known as: MK2206

Treatment (MK2206, anastrozole, goserelin acetate)

Anastrozole DRUG

Given PO

Also known as: Anastrazole, Arimidex, ICI D1033, ICI-D1033, ZD-1033

Treatment (MK2206, anastrozole, goserelin acetate)

Goserelin Acetate DRUG

Given SC

Also known as: ZDX, Zoladex

Treatment (MK2206, anastrozole, goserelin acetate)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (MK2206, anastrozole, goserelin acetate)

Neoadjuvant Therapy PROCEDURE

Given before standard-care surgery

Also known as: Induction Therapy, Neoadjuvant, Preoperative Therapy

Treatment (MK2206, anastrozole, goserelin acetate)

Pharmacological Study OTHER

Correlative studies

Treatment (MK2206, anastrozole, goserelin acetate)

Therapeutic Conventional Surgery PROCEDURE

Undergo standard-care surgery

Treatment (MK2206, anastrozole, goserelin acetate)

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (8)

Mayo Clinic in Arizona

Scottsdale, Arizona, 85259, United States

Location

University of Chicago Comprehensive Cancer Center

Chicago, Illinois, 60637, United States

Location

University of Iowa/Holden Comprehensive Cancer Center

Iowa City, Iowa, 52242, United States

Location

Johns Hopkins University/Sidney Kimmel Cancer Center

Baltimore, Maryland, 21287, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Metro Minnesota Community Oncology Research Consortium

Saint Louis Park, Minnesota, 55416, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

University of Wisconsin Hospital and Clinics

Madison, Wisconsin, 53792, United States

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

MK 2206; Anastrozole; Goserelin; Neoadjuvant Therapy

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Nitriles; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Gonadotropin-Releasing Hormone; Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins; Combined Modality Therapy; Therapeutics

Results Point of Contact

• Title: Cynthia Ma, M.D., Ph.D.
• Organization: Washington University School of Medicine

cma@dom.wustl.edu

Study Officials

• Cynthia Ma

  Mayo Clinic Cancer Center P2C

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 23, 2013
• First Posted: January 25, 2013
• Study Start: January 1, 2013
• Primary Completion: May 1, 2015
• Study Completion: May 5, 2015
• Last Updated: May 8, 2018
• Results First Posted: May 8, 2018

Record last verified: 2018-04

Locations

US (8)