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Trial · Interventional

TerminatedPhase 2Results postedRegistry data

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

NCTNCT01776008 (opens ClinicalTrials.gov in a new tab)Other idNCI-2013-00080Other idNCI-2013-00080Other idMC1139Other idMC1139

Overview

Status
Terminated
Phase
Phase 2
Enrollment
16 participants (actual)
Sponsor
National Cancer Institute (NCI) · Nih
Design
Allocation not applicable · Open label (no masking)
Countries
1 country

United States

Start
Jan 2013
Primary completion
May 2015
Completion
5 May 2015
First posted
25 Jan 2013 (estimated)
Last update posted
8 May 2018
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

Timeline

1 trial · 1 stopped early · 1 with posted results

  • Completed
  • Ongoing
  • Not yet recruiting
  • Stopped
  • Estimated dates (est.)
  • Results posted
2013201420152016
  1. Ph 2

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

    NCT01776008

    Jan 2013 to 5 May 2015

    Terminated

Registry summary

Text and fields below are the sponsor's entries at ClinicalTrials.gov, shown as posted.

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.

Interventions

  • Akt Inhibitor MK2206Drug
  • AnastrozoleDrug
  • Goserelin AcetateDrug
  • Laboratory Biomarker AnalysisOther
  • Neoadjuvant TherapyProcedure
  • Pharmacological StudyOther
  • Therapeutic Conventional SurgeryProcedure

Arms1

  • 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.

Primary outcomes1

Outcomes the sponsor listed as primary.

  1. Pathological Complete Response Rate

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

    Registry description

    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.

Secondary outcomes(3)
  1. Clinical Response Rate

    Time frame · Baseline to end of Cycle 4 (28 day cycles)

    Registry description

    The Clinical response rate is estimated by the number of patients whose disease meets the WHO criteria of complete or partial response based on physical examination divided by the total number of eligible patients. Complete Response (CR) is defined as the disappearance of all known disease based on measurements taken at the completion of neo-adjuvant therapy. Partial Response (PR) is defined as a 50% or greater decrease in the product of the bi-dimensional measurements of the lesion (total tumor size) between the pre-treatment measurements and the measurements taken at the completion of neo-adjuvant therapy. A ninety percent confidence interval for the true clinical response rate will be calculated using the Duffy-Santer approach.

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

    Time frame · Baseline to end of Cycle 4 (28 day cycles)

    Registry description

    The maximum grade for each type of adverse event will be recorded for each patient, and frequency tables will be reviewed to determine patterns. For this endpoint, we are reporting the number of patients that reported a grade 3 or higher graded adverse event during neoadjuvent treatment. A complete list of all reported adverse events is in the Adverse Events section of the report.

  3. Radiological Response Rate

    Time frame · Baseline and completion of cycle 4 (28 day cycles)

    Registry description

    The Clinical response rate is estimated by the number of patients whose disease meets the WHO criteria of complete or partial response based on radiographic evaluation (mammogram or ultrasound) divided by the total number of eligible patients. Complete Response (CR) is defined as the disappearance of all known disease based on measurements taken at the completion of neo-adjuvant therapy. Partial Response (PR) is defined as a 50% or greater decrease in the product of the bi-dimensional measurements of the lesion (total tumor size) between the pre-treatment measurements and the measurements taken at the completion of neo-adjuvant therapy. A ninety percent confidence interval for the true clinical response rate will be calculated using the Duffy-Santer approach.

Posted results

Values are shown as posted at ClinicalTrials.gov, with their units. PepBank has not converted, pooled or compared them.

Primary outcome results

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

Pathological Complete Response Rate

GroupValue (participants)
Treatment (MK2206, Anastrozole, Goserelin Acetate)0
Secondary and other outcome results(7)
Secondary outcome· Baseline to end of Cycle 4 (28 day cycles)

Clinical Response Rate

GroupValue
Treatment (MK2206, Anastrozole, Goserelin Acetate)not posted
Secondary outcomeCount of participants· 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

GroupValue (Participants)
Treatment (MK2206, Anastrozole, Goserelin Acetate)6
Secondary outcome· Baseline and completion of cycle 4 (28 day cycles)

Radiological Response Rate

GroupValue
Treatment (MK2206, Anastrozole, Goserelin Acetate)not posted
Other pre specified outcome· 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

Change in Ki67 Levels

GroupValue
Treatment (MK2206, Anastrozole, Goserelin Acetate)not posted
Other pre specified outcome· 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

GroupValue
Treatment (MK2206, Anastrozole, Goserelin Acetate)not posted
Other pre specified outcome· 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%

GroupValue
Treatment (MK2206, Anastrozole, Goserelin Acetate)not posted
Other pre specified outcome· At baseline, following 4 weeks of anastrozole alone, day 1 of course 3, and at pre-surgery

Serum Estradiol Levels

GroupValue
Treatment (MK2206, Anastrozole, Goserelin Acetate)not posted

Adverse events, as posted

Adverse events as posted: participants affected out of participants at risk, by group
GroupDeathsSerious eventsOther events
Treatment (MK2206, Anastrozole, Goserelin Acetate)Patients receive 150 mg Akt inhibitor MK-2206 PO on days 2, 9, 16, and 23; 1 mg anastrozole PO daily on days 1-28; and 3.6 mg 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.0 / 161 / 1616 / 16

Each cell reads participants affected / participants at risk, as the registry posted them.

Registry data comes from ClinicalTrials.gov. Study results come from studies, not from the registry. How PepBank works

Studies0

Studies that cite this trial.

No study cites this trial.

Eligibility

Who could join, as posted.

Sex
Female
Age
from 18 Years
Healthy volunteers
Not accepted
Inclusion and exclusion criteria, as posted
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

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