Akt Inhibitor MK2206 in Treating Patients With Recurrent or Advanced Endometrial Cancer



Status:Active, not recruiting
Conditions:Cervical Cancer
Therapuetic Areas:Oncology
Healthy:No
Age Range:18 - Any
Updated:6/16/2016
Start Date:March 2011

Use our guide to learn which trials are right for you!

A Phase II, 2-Stage, 2-Arm PIK3CA Mutation Stratified Trial of MK-2206 in Recurrent or Advanced Endometrial Cancer

This phase II trial studies how well Akt inhibitor MK2206 works in treating patients with
recurrent or advanced endometrial cancer. Akt inhibitor MK2206 may stop the growth of tumor
cells by blocking some of the enzymes needed for cell growth.

PRIMARY OBJECTIVES:

I. To assess the activity of MK-2206 (Akt inhibitor MK2206) in patients with recurrent or
persistent endometrial cancer classified by phosphoinositide-3-kinase catalytic alpha
(PIK3CA) mutation. Activity will be ascertained by the proportion of patients who survive
progression-free for at least 6 months after initiating therapy or who have objective tumor
response.

II. To evaluate the efficacy of MK2206 in patients with serous tumors using a composite
endpoint of complete and partial response by Response Evaluation Criteria In Solid Tumors
(RECIST) and progression-free interval of 6 months or longer.

SECONDARY OBJECTIVES:

I. To determine the duration of progression-free survival and overall survival. II. To
determine the nature and degree of toxicity of MK-2206 as assessed by version 4 of the
National Cancer Institute (NCI) Common Terminology Criteria For Adverse Events (CTCAE) in
these cohorts of patients.

III. To explore the associations between select biomarkers and response to MK-2206 such as
progression-free survival, objective tumor response, and overall survival as well as patient
characteristics such as histological cell type.

IV. To explore the development of feed-back loop activation (post-treatment biopsy biomarker
analysis) and target inhibition using MK-2206 via analysis of pre-treatment and
post-treatment biopsies in select patients enrolled in the trial.

V. To determine the duration of progression-free and overall survival, following initiation
of therapy with MK-2206.

VI. To determine the toxicities of MK-2206, as assessed with the revised NCI CTCAE version
4.

VII. To explore the association between select biomarkers and response to MK-2206 such as
progression-free survival, objective tumor response.

OUTLINE:

Patients receive Akt inhibitor MK2206 orally (PO) once weekly. Courses repeat every 28 days
in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 3 years.

Inclusion Criteria:

- Participants must have histologically confirmed recurrent or persistent high grade
endometrial carcinoma with a serous component, which is refractory to curative
therapy or established treatments; histologic confirmation of the original primary
tumor is required

- All patients must have measurable disease as defined by RECIST 1.1; measurable
disease is defined as at least one lesion that can be accurately measured in at least
one dimension (longest diameter to be recorded); each lesion must be >= 10 mm when
measured by computed tomography (CT), magnetic resonance imaging (MRI) or caliper
measurement by clinical exam; or >= 20 mm when measured by chest x-ray; lymph nodes
must be >= 15 mm in short axis when measured by CT or MRI

- Patients must have had one prior chemotherapeutic regimen for management of
endometrial carcinoma initial treatment may include chemotherapy, chemotherapy and
radiation therapy, and/or consolidation/maintenance therapy; chemotherapy
administered in conjunction with primary radiation as a radio-sensitizer WILL be
counted as a systemic chemotherapy regimen

- Patients are allowed to receive, but are not required to receive, one additional
prior treatment regimen (including a single chemotherapeutic, a combination of
chemotherapeutics, or an anti-angiogenic drug such as bevacizumab) for management of
their recurrent or persistent disease; prior hormonal therapy is allowed and does not
count towards this prior regimen

- Patients must have NOT received any class of drugs targeted to the PI3K pathway (such
has PI3K inhibitors or mTOR inhibitors) for management of recurrent or persistent
disease

- Life expectancy of greater than 6 months

- Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 50%)

- Absolute neutrophil count >= 1,500/mcL

- Platelets >= 100,000/mcL

- Total bilirubin within normal institutional limits

- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase
[SGOT])/alanine aminotransferase (ALT) (serum glutamic pyruvate transaminase [SGPT])
=< 2.5 x institutional upper limit of normal

- Creatinine within normal institutional limits or creatinine clearance >= 60
mL/min/1.73 m^2 for subjects with creatinine levels about institutional normal

- Hemoglobin A1c (HgA1c) =< 7.5% and fasting blood glucose less than 130mg/dL

- Availability of a formalin fixed paraffin embedded (FFPE) block of cancer tissue from
the original or most recent biopsy for mutational analysis

- 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; should a patient become pregnant or suspect she is
pregnant while she is participating in this study, she should inform the treating
physician immediately

- Toxicities of prior therapy (excepting alopecia) should be resolved to =< grade 1 per
the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4

- MK-2206 is an oral medication; patients must be able to tolerate oral medications and
not have gastrointestinal illnesses that would preclude absorption of MK-2206

- Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

- Participants who have had chemotherapy or radiotherapy within 3 weeks (6 weeks for
nitrosoureas or mitomycin C) prior to entering the study or those who have not
recovered to =< grade 1 (excepting alopecia) from adverse events (as per the revised
NCI CTCAE version 4) due to agents administered more than 3 weeks earlier

- Participants may not be receiving any other study agents

- Participants with known brain metastases should be excluded from this clinical trial
because of their poor prognosis and because they often develop progressive neurologic
dysfunction that would confound the evaluation of neurologic and other adverse
events; should patients develop brain metastases while on trial and have clinical
benefit from MK-2206 otherwise, patients may continue on drug after clinical
management of the brain metastases with the permission of the principal investigator.
MK-2206 should be restarted between 3 and 6 weeks after the last radiation treatment

- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to MK-2206

- Patients requiring any medications or substances that are strong inhibitors or
inducers of CYP 450 3A4 are ineligible

- Preclinical studies demonstrated the potential of MK-2206 for induction of
hyperglycemia in all preclinical species tested; patients with diabetes or in risk
for hyperglycemia should not be excluded from trials with MK-2206, but the
hyperglycemia should be well controlled on oral agents before the patient enters the
trial. HgbA1c > 7.5% or fasting glucose greater than 130mg/dL will exclude patients
from entry on study; patients requiring insulin for control of their hyperglycemia
are excluded from entry on this study

- Preclinical studies indicated transient changes in QTc interval during MK-2206
treatment; prolongation of QTc interval is potentially a safety concern while on
MK-2206 therapy; cardiovascular: baseline QTcF > 450 msec (male) or QTcF > 470 msec
(female) will exclude patients from entry on study

- Due to a high incidence of bradycardia by Holter monitor, preexisting bundle branch
block or baseline bradycardia due to cardiac disease will exclude patients from
treatment with MK-2206

- 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; mother with MK-2206 breastfeeding should
be discontinued if the mother is treated with MK-2206; these potential risks may also
apply to other agents used in this study

- MK-2206 is an oral medication; patients who are unable to tolerate oral medication
are not eligible; patients with signs and symptoms of bowel obstruction or with
uncontrolled, persistent diarrhea will be excluded

- Individuals with a history of a different malignancy are ineligible except for the
following circumstances. Individuals with a history of other malignancies are
eligible if they have been disease-free for at least 5 years and are deemed by the
investigator to be at low risk for recurrence of that malignancy. Individuals with
the following cancers are eligible if diagnosed and treated within the past 5 years:
breast cancer in situ, cervical cancer in situ, and basal cell or squamous cell
carcinoma of the skin

- Human immunodeficiency virus (HIV)-positive individuals on combination antiretroviral
therapy are ineligible

- Patients may not use natural herbal products or other "folk remedies" while
participating in this study
We found this trial at
7
sites
Houston, Texas 77030
?
mi
from
Houston, TX
Click here to add this to my saved trials
330 Brookline Ave
Boston, Massachusetts 02215
617-667-7000
Beth Israel Deaconess Medical Center Beth Israel Deaconess Medical Center (BIDMC) is one of the...
?
mi
from
Boston, MA
Click here to add this to my saved trials
450 Brookline Ave
Boston, Massachusetts 2215
617-632-3000
Dana-Farber Cancer Institute Since it’s founding in 1947, Dana-Farber has been committed to providing adults...
?
mi
from
Boston, MA
Click here to add this to my saved trials
55 Fruit St
Boston, Massachusetts 02114
(617) 724-4000
Massachusetts General Hospital Cancer Center An integral part of one of the world
?
mi
from
Boston, MA
Click here to add this to my saved trials
Charlestown, Massachusetts 02129
?
mi
from
Charlestown, MA
Click here to add this to my saved trials
1275 York Ave
New York, New York 10021
(212) 639-2000
Memorial Sloan Kettering Cancer Center Memorial Sloan Kettering Cancer Center — the world's oldest and...
?
mi
from
New York, NY
Click here to add this to my saved trials
2014 Washington St
Newton, Massachusetts 02462
(617) 243-6000
Newton-Wellesley Hospital A comprehensive medical center located right in Newton on Washington Street, Newton-Wellesley Hospital...
?
mi
from
Newton, MA
Click here to add this to my saved trials