PIK3CA Mutation Stratified Trial of MK-2206 in Recurrent or Advanced Endometrial Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Massachusetts General Hospital
Memorial Sloan-Kettering Cancer Center
M.D. Anderson Cancer Center
Information provided by (Responsible Party):
Panagiotis Konstantinopoulos, MD, PhD, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier:
NCT01312753
First received: December 30, 2010
Last updated: February 10, 2014
Last verified: February 2014
  Purpose

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.

Based on results from the initial cohort in MK2206, an independent cohort of patients with endometrial serous histology has been added to this study.


Condition Intervention Phase
Endometrial Cancer
Drug: MK-2206
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II, 2-Stage, 2-Arm PIK3CA Mutation Stratified Trial of MK-2206 in Recurrent or Advanced Endometrial Cancer

Resource links provided by NLM:


Further study details as provided by Dana-Farber Cancer Institute:

Primary Outcome Measures:
  • Activity [ Time Frame: 2 years ] [ Designated as safety issue: No ]

    For 'Two-Stage Designs within PIK3CA-Defined Strata":To assess the activity of MK-2206 in this patient population classified by 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.

    For "Single-stage Design within High-Grade Serous Histology": To evaluate the efficacy of MK2206 in patients with serous tumors using a composite endpoint of complete and partial response by RECIST and progression-free interval of 6 months or longer.



Secondary Outcome Measures:
  • Progression-Free Survival [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    To determine the duration of progression-free survival.

  • Toxicity [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
    To determine the nature and degree of toxicity of MK-2206 as assessed by version 4 of the NCI CTCAE in these cohorts of patients.

  • Overall Survival [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    To determine the duration of overall survival

  • Biomarkers [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    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.

  • Target Inhibition [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    To explore the development of feed-back loop activation (post-treatment biopsy biomarker analysis) and target inhibition using MK-2206 via analysis of pretreatment and post-treatment biopsies in select patients enrolled in the trial.


Estimated Enrollment: 90
Study Start Date: March 2011
Estimated Primary Completion Date: January 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: PIK3CA Mutation
Tumors harbor PIK3CA mutation. 135 mg MK-2206 tablets, orally dosed weekly.
Drug: MK-2206
135 mg MK-2206 tablets, orally dosed weekly.
Experimental: PIK3CA Wildtype
Tumor is PIK3CA wildtype. 135 mg MK-2206 tablets, orally dosed weekly.
Drug: MK-2206
135 mg MK-2206 tablets, orally dosed weekly.
Experimental: High-Grade Serous Histology
Based on results from the initial cohort in MK2206, an independent cohort of patients with endometrial serous histology has been added to this study. 135 mg MK-2206 tablets, orally dosed weekly.
Drug: MK-2206
135 mg MK-2206 tablets, orally dosed weekly.

Detailed Description:
  • Participants will take the study drug, MK-2206, orally once a week. Each treatment cycle lasts four weeks (28 days). Participants will be asked to complete a drug diary stating when they took each dose and to give a reason if they did not take the drug. At the end of each cycle, participants will be asked to return the pill bottles and all of the remaining pills before starting the next cycle.
  • At the beginning of each cycle the following procedures and tests will be performed: physical exam, evaluation of performance status, blood samples. Once a week for the first two cycles the following procedures and tests will be performed: participant will be called at home by a member of the study team to record any health problems, including side effects from the study drugs and blood samples.
  • A CT scan or MRI of the chest, stomach area, and pelvis will be performed every 2 cycles to see if the cancer is increasing, decreasing, or staying the same size.
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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 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

Exclusion Criteria:

  • 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 trial
  • 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 study requirements.
  • 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 study
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01312753

Locations
United States, Massachusetts
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02215
Massachusetts General Hospital
Boston, Massachusetts, United States, 02214
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States, 02115
Newton-Wellesley Hospital
Newton, Massachusetts, United States, 02462
United States, New York
Memorial Sloan-Kettering
New York, New York, United States
United States, Texas
MD Anderson Cancer Center
Houston, Texas, United States
Sponsors and Collaborators
Dana-Farber Cancer Institute
Massachusetts General Hospital
Memorial Sloan-Kettering Cancer Center
M.D. Anderson Cancer Center
Investigators
Principal Investigator: Panagiotis Konstantinopoulos, MD Dana-Farber Cancer Institute
  More Information

No publications provided

Responsible Party: Panagiotis Konstantinopoulos, MD, PhD, Prinicipal Investigator, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier: NCT01312753     History of Changes
Other Study ID Numbers: 10-258
Study First Received: December 30, 2010
Last Updated: February 10, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Dana-Farber Cancer Institute:
PIK3CA mutation
PIK3CA wildtype
MK-2206
High grade
Serous

Additional relevant MeSH terms:
Endometrial Neoplasms
Uterine Neoplasms
Genital Neoplasms, Female
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Uterine Diseases
Genital Diseases, Female

ClinicalTrials.gov processed this record on August 20, 2014