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A Phase Ib Trial of MK-2206 (an AKT Inhibitor) in Combination With Endocrine Therapy in Patients With Hormone Receptor Positive Breast Cancer

Phase 1
18 Years
Not Enrolling
Carcinoma Breast Stage IV

Thank you

Trial Information

A Phase Ib Trial of MK-2206 (an AKT Inhibitor) in Combination With Endocrine Therapy in Patients With Hormone Receptor Positive Breast Cancer

The phase II portion of this trial will be listed under a separate NCT number.

Inclusion Criteria:

1. Patient must have clinical stage IV invasive mammary carcinoma, previously documented
by histological analysis, which is ER-positive and/or PR-positive by
immunohistochemistry (IHC), which had previous endocrine therapy in the metastatic
setting or had metastatic recurrence within 6 months of adjuvant endocrine therapy.
Patients may have either measurable or non-measurable disease, both are allowed. Any
number of prior hormone or chemotherapy agents are acceptable

2. Patient is female and ≥ 18 years of age on the day of signing informed consent

3. Patient must have performance status of 0 or 1 on the ECOG Performance Scale

4. Patient must have adequate organ function as indicated by the following laboratory


- Absolute neutrophil count (ANC) ≥ 1,500 /μL

- Platelets ≥ 100,000 /μL

- Hemoglobin ≥ 9 g/dL


-Serum creatinine or calculated creatinine clearance† - ≤ 1.5 x upper limit of normal
(ULN) OR ≥60 mL/min for patients with creatinine levels > 1.5 x institutional ULN


- Serum total bilirubin ≤ 1.5 x ULN OR direct bilirubin ≤ ULN for patients with
total bilirubin levels > 1.5 x ULN

- AST (SGOT) and ALT (SGPT) ≤ 2.5 x ULN or ≤5 x ULN in patients with known liver


- Prothrombin time (PT)/INR ≤ 1.2 x ULN

- Partial thromboplastin time (PTT) ≤ 1.2 x ULN


-HBA1C ≤ 8%

† Creatinine clearance should be calculated per institutional standard

‡ Fasting is defined as at least 8 hours without oral intake

5. Female patient of childbearing potential must have a negative serum or urine
pregnancy test β-hCG within 72 hours prior to receiving the first dose of study

6. Post-menopausal female subjects should be defined prior to protocol enrollment by any
of the following:

- Subjects at least 55 years of age

- Subjects under 55 years of age and amenorrheic for at least 12 months or
follicle-stimulating hormone (FSH) values ≥ 40 IU/L and estradiol levels < or
equal to 20IU/L

- Prior bilateral oophorectomy or prior radiation castration with amenorrhea for
at least 6 months

7. Patient, or the patient's legal representative, has voluntarily agreed to participate
by giving written informed consent

8. Patient is able to swallow capsules and has no surgical or anatomical condition that
will preclude the patient from swallowing and absorbing oral medications on an
ongoing basis

9. Patients may receive concurrent radiation therapy to painful bone metastases or areas
of impending bone fracture as long as radiation therapy is initiated prior to study
entry. Patients who have received prior radiotherapy must have recovered from any
toxicity induced by this treatment (toxicity grade ≤ 1)

Exclusion Criteria:

1. Patient who has had chemotherapy, radiotherapy, or biological therapy within 3 weeks
(6 weeks for nitrosoureas, mitomycin C or bevacizumab), or who has not recovered from
the adverse events due to previous agents administered more than 4 weeks prior to
Study Day 1. If the patient has residual toxicity from prior treatment,toxicity must
be ≤ Grade 1

2. Patients must be at least 4 weeks post major surgical procedure, and all surgical
wounds must be fully healed

3. Patient is currently participating or has participated in a study with an
investigational compound or device within 30 days of Study Day 1

4. Patient has known active CNS metastases and/or carcinomatous meningitis. However,
patients with CNS metastases who have completed a course of therapy would be eligible
for the study provided they are clinically stable for at least 1 month prior to entry
as defined as: (1) no evidence of new or enlarging CNS metastasis (2)off steroids
that are used to minimize surrounding brain edema

5. Patient has a primary central nervous system tumor

6. Patient has known hypersensitivity to the components of study drug or its analogs

7. Patient has a history or current evidence of clinically significant heart disease

- Clinically significant congestive heart failure, unstable angina pectoris,

- Clinically significant cardiac arrhythmia,

- history or current evidence of a myocardial infarction during the last 6
months,and/or a current ECG tracing that is abnormal in the opinion of the
treating Investigator,

- baseline QTc prolongation > 450 msec (Bazett's Formula). Medications included in
Arizona CERT Lists 1 and 2 (Appendix D) must be excluded. The concomitant use of
drugs that are associated with increased risk for QT prolongation should be
avoided in patients with congenital long QT syndrome (Appendix D, Arizona CERT
List 3). Similarly, the concomitant use of drugs that are weakly associated with
QT prolongation should be generally avoided (Appendix D, Arizona CERT List 4).
Arizona CERT List 3 and 4 drugs should be used at the discretion of the
Investigator and restricted where applicable. Any therapy given with these drugs
should be used with caution, and patients receiving these medications should be
carefully monitored.

8. Patient with evidence of clinically significant bradycardia (HR <50), or a history of
clinically significant bradyarrhythmias such as sick sinus syndrome, 2nd degree AV
block (Mobitz Type 2), or patients taking beta blockers, non-dihydropyridine calcium
channel blockers, or digoxin

9. Patient with uncontrolled hypertension (i.e., 160/90 mHg SiBP). Patients who are
controlled on antihypertensive medication will be allowed to enter the study

10. Patient at significant risk for hypokalemia (e.g., patients on high dose diuretics,
or with recurrent diarrhea)

11. Patient with poorly controlled diabetes defined as HbA1C > 8%

12. Patient has a history or current evidence of any condition, therapy, or lab
abnormality that might confound the results of the study, interfere with the
patient's participation for the full duration of the study, or is not in the best
interest of the patient to participate, in the opinion of the treating Investigator

13. Patient has known psychiatric or substance abuse disorders that would interfere with
cooperation with the requirements of the trial

14. Patient is, at the time of signing informed consent, a regular user (including
"recreational use") of any illicit drugs or had a recent history (within the last
year) of drug or alcohol abuse

15. Patient is pregnant or breastfeeding, or expecting to conceive or father children
within the projected duration of the study

16. Patient is known to be Human Immunodeficiency Virus (HIV)-positive

17. Patient has known history of Hepatitis B or C or active Hepatitis A Experimental
agent: MK-2206

18. Patient has symptomatic ascites or pleural effusion. A patient who is clinically
stable following treatment for these conditions is eligible

19. Patient is receiving treatment with oral corticosteroids (note: inhaled
corticosteroids are permitted)

Type of Study:


Study Design:

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Tolerability of MK-2206 given in combination with exemestane +/- goserelin in pre-and-post-menopausal patients with hormone receptor positive metastatic breast cancer, as measured by maximum tolerated dose (MTD).

Outcome Description:

The maximum tolerated dose will be defined as the highest dose tested in which a DLT is experienced by 0 out of 3 or 1 out of 6 patients among the dose levels.

Outcome Time Frame:

Completion of chemotherapy in last cohort

Safety Issue:


Principal Investigator

Vandana Abramson, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Vanderbilt-Ingram Cancer Center


United States: Food and Drug Administration

Study ID:




Start Date:

January 2011

Completion Date:

December 2012

Related Keywords:

  • Carcinoma Breast Stage IV
  • Breast Neoplasms
  • Carcinoma



Vanderbilt-Ingram Cancer Center Nashville, Tennessee  37232-6838