This trial is active, not recruiting.

Condition endometrial cancer
Treatment blood draw and biopsy
Sponsor M.D. Anderson Cancer Center
Collaborator National Cancer Institute (NCI)
Start date August 2014
End date August 2019
Trial size 25 participants
Trial identifier NCT02093546, 2013-1029


The goal of this study is to check the effect of trametinib alone and when given with GSK2141795 on biomarkers in patients with persistent or recurrent endometrial cancer. Biomarkers are found in the blood/tissue and may be related to your reaction or response to the study drug.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Observational model cohort
Time perspective prospective
Participant undergoes blood draw and biopsy prior to start of therapy. After 28 days of therapy, a blood draw and an additional biopsy of the same site obtained prior to beginning cycle 2. Blood draw obtained at first tumor assessment point at pre-cycle 3 and at progression. Participants undergo an additional blood draw at 72 hours after initiation of therapy. Participants offered an optional biopsy of the same site at 72 hours after initiation of therapy and at progression of disease. If participant undergoes biopsy at any timepoint during trial as part of standard of care treatment, tissue used for protocol assessment.
blood draw and biopsy
Participant undergoes tumor biopsy to check for biomarkers during screening and at Day 28. Blood drawn to test for biomarkers and CTCs between Day 3 and Day 5 and at Day 56.

Primary Outcomes

Impact of Trametinib Alone or in Combination with GSK2141795 on RAF-MEK-ERK and PI3K Pathway Signaling
time frame: 28 days

Secondary Outcomes

Comparison of Pre-Treatment to Post-Treatment Changes in Biomarker Expression
time frame: Between Day 3 and Day 5

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion Criteria: 1. Patients must be enrolled on GOG0229O. 2. Patients must have recurrent or persistent endometrial carcinoma, which is refractory to curative therapy or established treatments. Histologic confirmation of the original primary tumor is required. Patients with the following histologic epithelial cell types are eligible: Endometrioid adenocarcinoma, serous adenocarcinoma, undifferentiated carcinoma, mixed epithelial carcinoma, and adenocarcinoma not otherwise specified (N.O.S.). 3. Patients must have tissue available for molecular analysis. This can be tissue obtained at time of current recurrence or archival tissue from primary diagnosis or recurrence. 4. All patients must have measurable disease. Measurable disease is defined by Response Evaluation Criteria in Solid Tumors (RECIST). 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 CT, 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. Measurable disease lesions must be amenable to pre- and post- treatment biopsy. 5. Patients must have at least one "target lesion" to be used to assess response on this protocol as defined by RECIST. Tumors within a previously irradiated field will be designated as "non-target" lesions unless progression is documented or a biopsy is obtained to confirm persistence at least 90 days following completion of radiation therapy. 6. Patients must not be eligible for a higher priority Gynecologic Oncology Group (GOG) protocol, if one exists. In general, this would refer to any active GOG Phase III protocol or Rare Tumor protocol for the same patient population. 7. Patients must have a GOG Performance Status of 0 or 1. 8. Recovery from effects of recent surgery, radiotherapy, or chemotherapy a) Patients should be free of active infection requiring antibiotics (with the exception of uncomplicated UTI) b)Any hormonal therapy directed at the malignant tumor must be discontinued at least one week prior to registration c) Any other prior therapy directed at the malignant tumor, including chemotherapy and immunotherapy, must be discontinued at least three weeks prior to registration. Any investigational agent must be discontinued at least 30 days prior to registration d) Any prior radiation therapy must be discontinued at least four weeks prior to registration e) At least 4 weeks must have elapsed since the patient underwent any major surgery (e.g., major: laparotomy, laparoscopy) There is no delay in treatment for minor procedures (e.g., tumor core biopsy). 9. Patients must have had one prior chemotherapeutic regimen for management of endometrial carcinoma. Initial treatment may include chemotherapy, chemotherapy and radiation therapy, 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 cytotoxic regimen for management of recurrent or persistent disease. 10. Patients MAY HAVE received non-cytotoxic (biologic or targeted) agent(s) as part of initial treatment and/or for management of recurrent or persistent disease, with the below stated exceptions (see NOTE below). Prior hormonal therapy is allowed, but must be discontinued at least one week prior to registration. NOTE: Prior therapy with PI3K inhibitors, AKT inhibitors and/or mTor inhibitors (e.g., everolimus, temsirolimus) is NOT allowed. Prior therapy with MEK inhibitors (e.g., AZD6244 or selumetinib) is NOT allowed. 11. Patients must have adequate: a) Upper limit of normal (ULN) = institutional/laboratory upper limit of normal LLN = institutional/laboratory lower limit of normal b) Bone marrow function: Absolute neutrophil count (ANC) >/=1,500/mcl; Platelets >/=100,000/mcl; Hemoglobin >/=9 g/dl c) Renal function: Creatinine /=50 ml/min OR 24-hour urine creatinine clearance >/=50 ml/min d) Hepatic function: Bilirubin /=2.5g/dL e) Endocrine function: Fasting glucose < 160 mg/dL; Hemoglobin A1C (HbA1C) 160mg/dL at screening will be excluded. In addition, patients with Type 1 diabetes will also be excluded; however, patients with Type 2 diabetes will be allowed if diagnosed >/=6 months prior to enrollment, and if presenting with regular hemoglobin A1C (HbA1C) 21 mm Hg as measured by tonography 13. History or evidence of cardiovascular risk including any of the following: LVEF< LLN; A QT interval corrected for heart rate using the Bazett's formula QTcB >/= 480 msec; History or evidence of current clinically significant uncontrolled arrhythmias (exception: patients with controlled atrial fibrillation for >30 days prior to randomization are eligible); History of acute coronary syndromes (including myocardial Infarction and unstable angina), coronary angioplasty, or stenting within 6 months prior to randomization; History or evidence of current >/= Class II congestive heart failure as defined by the New York Heart Association (NYHA) functional classification system; Treatment-refractory hypertension defined as a blood pressure of systolic >140 mmHg or diastolic >90 mmHg which cannot be controlled by anti-hypertensive therapy; Known cardiac metastases; Subject with intra-cardiac defibrillator or pacemaker 14. 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 15. History of interstitial lung disease or pneumonitis

Additional Information

Official title A Translational Companion Protocol to GOG229O: A Randomized Phase II Study With a Safety Lead-in to Assess the Antitumor Efficacy of the MEK Inhibitor Trametinib Alone or in Combination With GSK2141795, an AKT Inhibitor, in Patients With Recurrent or Persistent Endometrial Cancer
Principal investigator Shannon Westin, MD
Description Study Visits: The following tests and procedures will be performed during your regular study visits while on GOG02290: During screening and at Day 28 (+/- 3 days): - You will have a tumor biopsy to check for biomarkers. - Blood (about 3 tablespoons) will be drawn to test for biomarkers and circulating tumor cells (CTCs). Biomarkers are found in the blood/tissue and may be related to your reaction to the study drug. CTC testing checks how many tumor cells are in the blood. Between Day 3 and Day 5 and at Day 56 (+/-3 days): -Blood (about 3 tablespoons) will be drawn to test for biomarkers and CTCs. Length of Study: After blood and biopsy samples have been collected, your participation in this study will be over. This is an investigational study. Up to 40 participants will be enrolled in this multicenter study. Up to 25 will take part at MD Anderson.
Trial information was received from ClinicalTrials.gov and was last updated in October 2016.
Information provided to ClinicalTrials.gov by M.D. Anderson Cancer Center.