Trametinib With or Without GSK2141795 in Treating Patients With Recurrent or Persistent Endometrial Cancer

Completed · Phase 1

Conditions studied: Endometrial Adenocarcinoma, Endometrial Clear Cell Adenocarcinoma, Endometrial Mixed Cell Adenocarcinoma, Endometrial Serous Adenocarcinoma, Endometrial Undifferentiated Carcinoma, Recurrent Uterine Corpus Cancer

In brief

This randomized phase I trial studies how well trametinib with or without GSK 2141795 (protein kinase B \[Akt\] inhibitor GSK2141795) works in treating patients with endometrial cancer that has come back (recurrent) or does not go to remission despite treatment (persistent). Trametinib and Akt inhibitor GSK2141795 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known whether trametinib is a more effective treatment for endometrial cancer when given with or without ATK inhibitor GSK2141795.

Key facts

Study ID

NCT01935973

Run by

National Cancer Institute (NCI)

People needed

26

Starts

2013-09-30

Expected to finish

2015-09-08

Last updated by the study team

2020-10-14

Who can join

Age: 18 and older. Sex: female. Healthy volunteers: not accepted.

You may qualify if…

• 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, uterine clear cell carcinoma, and adenocarcinoma not otherwise specified (N.O.S.)
• Formalin-fixed, paraffin-embedded tumor tissue must be submitted to Baylor College of Medicine (BCM) - Cancer Genetics Laboratory for Clinical Laboratory Improvement Amendments (CLIA)-certified KRAS mutation testing; results must be reported on the eligibility checklist during registration in order to receive treatment assignment
• Note: if CLIA-certified KRAS mutation tumor testing is available from local or other source (e.g., Foundation Medicine) this report can be submitted to Statistical and Data Center (SDC) to meet this requirement
• All patients must have measurable disease; measurable disease is defined by Response Evaluation Criteria in Solid Tumors (RECIST) (version 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 at least one "target lesion" to be used to assess response on this protocol as defined by RECIST version 1.1; 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
• Gynecologic Oncology Group (GOG) performance status of 0 or 1
• Recovery from effects of recent surgery, radiotherapy, or chemotherapy
• Patients should be free of active infection requiring antibiotics (with the exception of uncomplicated urinary tract infection [UTI])
• Any hormonal therapy directed at the malignant tumor must be discontinued at least one week prior to registration
• 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
• Any prior radiation therapy must be discontinued at least four weeks prior to registration
• 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)
• 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
• 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 mammalian target of rapamycin (mTor) inhibitors (e.g., everolimus, temsirolimus) is NOT allowed; prior therapy with MEK inhibitors (e.g., AZD6244 or selumetinib) is NOT allowed
• Absolute neutrophil count (ANC) >= 1,500/mcl
• Platelets >= 100,000/mcl
• Hemoglobin >= 9 g/dl
• Creatinine =< 1.5 x institutional/laboratory upper limit of normal (ULN) OR calculated creatinine clearance (Cockcroft-Gault formula) >= 50 ml/min OR 24-hour urine creatinine clearance >= 50 ml/min
• Bilirubin =< 1.5 x ULN
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x ULN
• Alkaline phosphatase =< 2.5 x ULN
• Albumin >= 2.5 g/dL

You may not qualify if…

• Patients who have had prior therapy with GSK2141795 or any other PI3K/AKT/MTOR pathway inhibitor
• Patients who have prior therapy with trametinib or any other MEK inhibitor
• Patients who have mucinous, squamous, sarcomas, or carcinosarcomas
• Patient with a history of other invasive malignancies, with the exception of non-melanoma skin cancer are excluded if there is any evidence of other malignancy being present within the last three years; patients are also excluded if their previous cancer treatment contraindicates this protocol eligibility
• Patients with symptomatic or untreated leptomeningeal or brain metastasis or spinal cord compression
• Patients with a history of interstitial lung disease or pneumonitis
• Patients with known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to the trametinib, GSK2141795 or dimethyl sulfoxide (DMSO)
• Current use of a prohibited medication; the following medications or non-drug therapies are prohibited:
• Other anti-cancer therapy while on study treatment
• Concurrent treatment with bisphosphonates is permitted; however, treatment must be initiated prior to the first dose of study therapy; prophylactic use of bisphosphonates in patients without bone disease is not permitted, except for the treatment of osteoporosis
• The concurrent use of all herbal supplements is prohibited during the study (including, but not limited to, St. John's Wort, kava, ephedra [ma huang], gingko biloba, dehydroepiandrosterone [DHEA], yohimbe, saw palmetto, or ginseng)
• Drugs that potently inhibit cytochrome P450 family 3, subfamily A, polypeptide 4 (CYP3A4) should be prohibited or used with caution; drugs which are strong inducers of CYP3A and may result in lower exposures of GSK2141795 should also be prohibited; drugs that are substrates of CYP3A4 or cytochrome P450 family 2, subfamily C, polypeptide 8 (CYP2C8) with a narrow therapeutic index may be prohibited; drugs that are sensitive substrates of CYP3A4 or CYP2C8 should be used with caution
• Caution should be exercised when dosing trametinib concurrently with medications with narrow therapeutic windows that are substrates of CYP2C8; drugs that potently inhibit or induce CYP3A4 should be administered with caution
• Because the lists of these agents are constantly changing, it is important to regularly consult a frequently-updated list such as http://medicine.iupui.edu/clinpharm/ddis/table.aspx; medical reference texts such as the Physicians' Desk Reference may also provide this information; as part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product
• The following medications (including but not limited to) are prohibited during the study:
• PROHIBITED-highly sensitive and/or low therapeutic index
• Cisapride
• Pimozide
• Astemizole
• Rosuvastatin, sulfasalazine
• PROHIBITED-strong inducers/inhibitors of CYP3A4
• Clarithromycin, telithromycin, rifamycin class agents (e.g., rifampin, rifabutin, rifapentine), troleandomycin
• Itraconazole, ketoconazole
• Nefazodone
• Atazanavir, delavirdine, indinavir, lopinavir, nelfinavir, ritonavir, saquinavir, nevirapine

Where it is running

• Hartford Hospital — Hartford, Connecticut, United States
• The Hospital of Central Connecticut — New Britain, Connecticut, United States
• Augusta University Medical Center — Augusta, Georgia, United States
• University of Chicago Comprehensive Cancer Center — Chicago, Illinois, United States
• University of Kentucky/Markey Cancer Center — Lexington, Kentucky, United States
• Johns Hopkins University/Sidney Kimmel Cancer Center — Baltimore, Maryland, United States
• Washington University School of Medicine — St Louis, Missouri, United States
• University of New Mexico Cancer Center — Albuquerque, New Mexico, United States
• Memorial Sloan Kettering Cancer Center — New York, New York, United States
• Carolinas Medical Center/Levine Cancer Institute — Charlotte, North Carolina, United States
• Case Western Reserve University — Cleveland, Ohio, United States
• Cleveland Clinic Foundation — Cleveland, Ohio, United States
• Ohio State University Comprehensive Cancer Center — Columbus, Ohio, United States
• Hillcrest Hospital Cancer Center — Mayfield Heights, Ohio, United States
• University of Oklahoma Health Sciences Center — Oklahoma City, Oklahoma, United States
• Thomas Jefferson University Hospital — Philadelphia, Pennsylvania, United States
• Fox Chase Cancer Center — Philadelphia, Pennsylvania, United States
• Women and Infants Hospital — Providence, Rhode Island, United States
• Medical University of South Carolina — Charleston, South Carolina, United States
• M D Anderson Cancer Center — Houston, Texas, United States
• University of Virginia Cancer Center — Charlottesville, Virginia, United States
• Virginia Commonwealth University/Massey Cancer Center — Richmond, Virginia, United States

Full record on ClinicalTrials.gov

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