PIK3CA Mutation Stratified Trial of MK-2206 in Recurrent or Advanced Endometrial Cancer
Phase: Phase 2
Diagnosis: GYN: Endometrial/Uterine Cancer
NCT ID: NCT01312753
(View complete trial on ClinicalTrials.gov)
DFCI Protocol ID: 10-258
MK-2206 is a drug that may stop cancer cells from growing. MK-2206 blocks a signal inside the cell that can cause abnormal cell growth. This drug has been used in other research studies and information from those studies suggests that this agent may help to keep cancer from growing in this research study. The investigators are looking to see how effective MK-2206 is in treating recurrent and metastatic endometrial cancer. Additionally, the investigators are looking to see if participants whose tumors contain a particular genetic make-up will have a better response to MK-2206. Participants' tumors will be tested for a mutation in a gene called PIK3CA, which makes a protein that helps cell to use energy and grow.
Dana-Farber Cancer Institute, Massachusetts General Hospital, Beth-Israel Deaconess Medical Center, Newton-Wellesley Hospital
Panagiotis Konstantinopoulos, MD,
Dana-Farber Cancer Institute
Mary Buss, MD,
Beth Israel Deaconess Medical Center
Michael Birrer, MD, PhD,
Massachusetts General Hospital
Caroline Block, MD,
Dana-Farber Cancer Institute:
Christin Whalen, 617-582-7738,
Beth-Israel Deaconess Medical Center:
Cancer Trials Call Center, 617-667-3060
Massachusetts General Hospital:
Cancer Trials Call Center, 877-789-6100
- Histologically confirmed recurrent or persistent endometrial carcinoma, which is
refractory to curative therapy or established treatments.
- 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 at least 10 mm
when measured by CT, MRI or caliper measurement by clinical exam; or at least 20 mm
when measured by chest x-ray. Lymph nodes must be at least 15 mm in short axis when
measured by CT or MRI.
- Patients must have had at least one prior chemotherapeutic regimen for management of
endometrial carcinoma. Initial treatment may include chemotherapy, chemotherapy and
radiation therapy, and/or consolidation/maintenance therapy.
- Patients must have not received any class of drugs targeted to the PI3K pathway
(including mTOR inhibitors) for management of recurrent or persistent disease.
- 18 years of age or greater
- Life expectancy of greater than 6 months
- ECOG performance status of 0, 1 or 2
- Normal organ and marrow function as outlined in the protocol
- Availability of formalin fixed paraffin embedded block of cancer tissue from the
original or most recent biopsy for mutational analysis
- Women of childbearing potential must use two forms of contraception prior to study
entry and for the duration of study participation.
- Toxicities of prior therapy (excepting alopecia) should be resolved to grade 1 or
lower per CTCAE version 4.
- Subjects with treated limited-stage basal cell or squamous cell carcinoma of the skin
or carcinoma in situ of the breast or cervix are eligible. Subjects with stage I or
II cancer treated with curative intent with no evidence of recurrent disease 5 years
following diagnosis are eligible.
- Patients must be able to tolerate oral medications and not have gastrointestinal
illnesses that would preclude absorption of MK-2206
- Participants who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for
nitrosoureas or mitomycin C) prior to entering the study or those who have not
recovered to Grade 1 or less from adverse events due to agents administered more than
4 weeks earlier.
- Participants may not be receiving any other study agents
- Participants with known brain metastases
- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to MK-2206
- Patients who require medications or substances that are strong inhibitors of inducers
of CYP 450 3A4
- Patients with diabetes or in risk of hyperglycemia should not be excluded, but the
hyperglycemia should be well controlled on oral agents before the patient enters the
- Baseline QTcF > 470msec
- 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
- Pregnant or breastfeeding women
- Patients who are unable to tolerate oral medication. Patients with signs and
symptoms of bowel obstruction or with uncontrolled, persistent diarrhea.
- HIV-positive individuals on combination antiretroviral therapy
- Patients may not use any natural herbal products or other "folk remedies" while on