Translational Companion Protocol to GOG229O
This trial is active, not recruiting.
|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|
|Boston, MA||Dana Farber Cancer Institute||no longer recruiting|
|St Louis, MO||Washington University||no longer recruiting|
|New York, NY||Memorial Sloan Kettering Cancer Center||no longer recruiting|
|Houston, TX||University of Texas MD Anderson Cancer Center||no longer recruiting|
Impact of Trametinib Alone or in Combination with GSK2141795 on RAF-MEK-ERK and PI3K Pathway Signaling
time frame: 28 days
Comparison of Pre-Treatment to Post-Treatment Changes in Biomarker Expression
time frame: Between Day 3 and Day 5
Male or female participants at least 18 years old.
- Patients must be enrolled on GOG0229O.
- 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.).
- 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.
- 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.
- 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.
- 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.
- Patients must have a GOG Performance Status of 0 or 1.
- 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).
- 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 mTor inhibitors (e.g., everolimus, temsirolimus) is NOT allowed. Prior therapy with MEK inhibitors (e.g., AZD6244 or selumetinib) is NOT allowed.
- 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 </=1.5 x ULN OR calculated creatinine clearance (Cockcroft-Gault formula) >/=50 ml/min OR 24-hour urine creatinine clearance >/=50 ml/min d) Hepatic function: Bilirubin </=1.5 x ULN; AST and ALT </=2.5 x ULN; Alkaline phosphatase </= 2.5 x ULN; Albumin >/=2.5g/dL e) Endocrine function: Fasting glucose < 160 mg/dL; Hemoglobin A1C (HbA1C) </= 8; TSH within institutional/laboratory normal limits f) Cardiac function: Left ventricular ejection fraction (LVEF) greater than or equal to LLN by ECHO or MUGA g) Coagulation Factors: International normalized ratio (INR) and partial thromboplastin time (PTT) </=1.5 x ULN
- All prior treatment-related toxicities must be CTCAE v4 grade </=1 (except alopecia) at the time of randomization.
- Patients with abnormal fasting glucose values >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) </=8% at screening.
- Patients must be able to swallow and retain orally-administered medication and must not have any clinically significant gastrointestinal abnormalities that may alter absorption such as malabsorption syndrome or major resection of the stomach or bowels.
- The effects of trametinib on the developing human fetus are unknown. For this reason and because MEK inhibitors as well as GSK2141795 are known to be teratogenic, women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Women of child-bearing potential must have a negative serum pregnancy test within 14 days prior to randomization. Should a woman become pregnant or suspect she is pregnant while she is participating in this study, she should inform her treating physician immediately.
- Patients must be 18 years or older. Because no dosing or adverse event data are currently available on the use of trametinib in combination with GSK2141795 in patients <18 years of age, children are excluded from this study, but will be eligible for future pediatric trials.
- Patients must have signed an approved informed consent and authorization permitting release of personal health information.
- 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 uterine clear cell, mucinous, squamous, transitional cell, 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 five years. Patients are also excluded if their previous cancer treatment contraindicates this protocol therapy.
- Use of other investigational drugs within 28 days (or five half-lives, whichever is shorter; with a minimum of 14 days from the last dose) preceding the first dose of trametinib and during the study.
- Patients with history or evidence upon physical exam of central nervous system disease (CNS), including primary brain tumor or seizures not controlled with standard medical therapy. Symptomatic or untreated leptomeningeal or brain metastasis or spinal cord compression.
- Patients who are pregnant or nursing.
- Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to the study drug or dimethyl sulfoxide (DMSO). To date there are no known FDA approved drugs chemically related to the investigational study drugs.
- Patients with gastrointestinal conditions that might predispose for drug intolerability or poor drug absorption (e.g., inability to take oral medication or a requirement for IV alimentation, prior surgical procedures affecting absorption, malabsorption syndrome, and active peptic ulcer disease) are excluded. Subjects with ulcerative colitis, inflammatory bowel disease, or a partial or complete small bowel obstruction are also excluded, as are any patients who cannot swallow the capsule whole. Capsules must not be crushed or chewed; naso-gastric or G-tube administration is not allowed.
- Known Hepatitis B Virus (HBV) or Hepatitis C Virus (HCV) infection (unless cleared) will be excluded.
- Current use of a prohibited medication. The following medications or non-drug therapies are prohibited: a)Other anti-cancer therapy while on study treatment. (Note: megestrol [Megace] if used as an appetite stimulant is allowed). b) 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. c) Because the composition, PK, and metabolism of many herbal supplements are unknown, 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).
- History or current evidence/risk of Retinal Vein Occlusion (RVO) or Central Serous Retinopathy (CSR): History of RVO or CSR, or predisposing factors to RVO or CSR (e.g. uncontrolled glaucoma or ocular hypertension, uncontrolled systemic disease such as hypertension, diabetes mellitus, or history of hyper viscosity or hyper coagulability syndromes); Visible retinal pathology as assessed by ophthalmic exam that is considered a risk factor for RVO or CSR such as: Evidence of new optic disc cupping; Evidence of new visual field defects on automated perimetry; Intraocular pressure > 21 mm Hg as measured by tonography
- 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
- 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
- History of interstitial lung disease or pneumonitis
|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.|
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