Paclitaxel, Carboplatin, and Bevacizumab or Paclitaxel, Carboplatin, and Temsirolimus or Ixabepilone, Carboplatin, and Bevacizumab in Treating Patients With Stage III, Stage IV, or Recurrent Endometrial Cancer
Endometrial Adenocarcinoma, Endometrial Adenosquamous Carcinoma, Endometrial Clear Cell Adenocarcinoma
About this trial
This is an interventional treatment trial for Endometrial Adenocarcinoma
Eligibility Criteria
Inclusion Criteria:
Patients must have measurable stage III, measurable stage IVA, stage IVB (with or without measurable disease) or recurrent (with or without measurable disease) endometrial carcinoma
- 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, clear cell adenocarcinoma, mixed epithelial carcinoma, adenocarcinoma not otherwise specified (N.O.S.), mucinous adenocarcinoma, squamous cell carcinoma, and transitional cell carcinoma
- 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 Gynecologic Oncology Group (GOG) performance status of 0, 1, or 2
- Patients must not be eligible for a higher priority 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
- Absolute neutrophil count (ANC) greater than or equal to 1,500/mcl equivalent to Common Terminology Criteria (CTCAE v3.0) grade 1
- Platelets greater than or equal to 100,000/mcl
- Creatinine less than or equal to 1.5 times institutional upper limit normal (ULN), CTCAE v3.0 grade 1
- Bilirubin less than or equal to 1.5 x ULN (CTCAE v3.0 grade 1)
- Serum glutamic oxaloacetic transaminase (SGOT) and serum glutamate pyruvate transaminase (SGPT) less than or equal to 2.5 x ULN (CTCAE v3.0 grade 1)
- Alkaline phosphatase less than or equal to 2.5 x ULN (CTCAE v3.0 grade 1)
Urine protein creatinine (UPC) ratio must be < 1.0 gram (gm); if UPC ratio >= 1, collection of 24-hour urine measurement of urine protein is recommended (24-hour urine protein level must be < 1000 mg for patient enrollment)
UPC ratio of spot urine is an estimation of the 24 urine protein excretion
- A UPC ratio of 1 is roughly equivalent to a 24-hour urine protein of 1 gm
- Prothrombin time (PT) such that international normalized ratio (INR) is =< 1.5 x ULN (or an in-range INR, usually between 2 and 3, if a patient is on a stable dose of therapeutic warfarin) and a partial thromboplastin time (PTT) =< 1.5 x ULN
- Fasting cholesterol less than 300 mg/dL (CTCAE v3.0 grade 1)
- Fasting triglycerides =< 2.5 x ULN (CTCAE v3.0 grade 1)
- Patients must NOT have received prior chemotherapy or targeted therapy, including chemotherapy used for radiation sensitization for treatment of endometrial carcinoma
- Patients must NOT have received prior therapy with bevacizumab or other VEGF pathway targeted therapy; patients must NOT have received prior therapy with temsirolimus, everolimus, ridaforolimus, sirolimus, or any other PI3K/ v-akt murine thymoma viral oncogene homolog 1 (AKT)/mammalian target of rapamycins (mTor) pathway targeted therapy
- Patients may have receive prior radiation therapy for treatment of endometrial carcinoma; prior radiation therapy may have included pelvic radiation therapy, extended field pelvic/para-aortic radiation therapy, and/or intravaginal brachytherapy; all radiation therapy must be completed at least 4 weeks prior to the first date of study therapy; the prior radiation field, radiation dose, number of fractions and prior radiation start and stop dates must be provided on the Fast Fact Sheet (FFS) at registration
- Patients may have received prior hormonal therapy for treatment of endometrial carcinoma; all hormonal therapy must be discontinued at least one week prior to the first date of study therapy
- Patients must have signed an approved informed consent and authorization permitting release of personal health information
Exclusion Criteria:
- Patients with a history of other invasive malignancies, with the exception of non-melanoma skin cancer, and other specific malignancies as noted below, 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 therapy
- Patients who have received prior radiotherapy to any portion of the abdominal cavity or pelvis OTHER THAN for the treatment of endometrial cancer within the last three years are excluded; prior radiation for localized cancer of the breast, head and neck, or skin is permitted, provided that it was completed more than three years prior to registration, and the patient remains free of recurrent or metastatic disease
- Patients who have received prior chemotherapy for any abdominal or pelvic tumor within the last three years are excluded; patients may have received prior adjuvant chemotherapy for localized breast cancer, provided that it was completed more than three years prior to registration, and that the patient remains free of recurrent or metastatic disease
- Patients with serious, non-healing wound, ulcer, or bone fracture; this includes history of abdominal/pelvic fistula, gastrointestinal perforation or intra-abdominal abscess within 3 months prior to the first date of study therapy; patients with underlying lesions that caused the fistula or perforation in the past that have not been corrected
- Patients with active bleeding or pathologic conditions that carry high risk of bleeding, such as known bleeding disorder, coagulopathy, or tumor involving major vessels
- Patients with history or evidence upon physical examination of central nervous system (CNS) disease, including primary brain tumor, seizures not controlled with standard medical therapy or any brain metastases
Patients with clinically significant cardiovascular disease; this includes:
- Uncontrolled hypertension, defined as systolic > 150 mm Hg or diastolic > 90 mm Hg
- Myocardial infarction or unstable angina within 6 months of the first date of study therapy
- New York Heart Association (NYHA) class II or greater congestive heart failure
- History of serious ventricular arrhythmia (i.e., ventricular tachycardia or ventricular fibrillation) or cardiac arrhythmias requiring anti-arrhythmic medications (except for atrial fibrillation that is well controlled with anti-arrhythmic medication)
- CTCAE grade 2 or greater peripheral vascular disease.
- History of cerebrovascular accident (CVA, stroke), transient ischemic attack (TIA) or subarachnoid hemorrhage within six months of the first date of study therapy.
- Aortic aneurysm and/or history of aortic dissection
- Patients with known hypersensitivity to Chinese hamster ovary cell products or other recombinant human or humanized antibodies
Patients undergoing invasive procedures as defined below:
- Major surgical procedure, open biopsy or significant traumatic injury within 28 days prior to the first date of bevacizumab or temsirolimus therapy
- Major surgical procedure anticipated during the course of the study.
- Minor surgical procedures, fine needle aspirates, or core biopsies within 7 days prior to the first date of study therapy
- Patients with known prior history of interstitial pneumonitis
- Patients with CTCAE v. 3, grade 2 or greater hypoxemia
- Patients with CTCAE v. 3, grade 2 or greater dyspnea
- Patients must not have uncontrolled diabetes, and must not have baseline hemoglobin A1C (HgbA1C) > 8
- Patients with peripheral neuropathy > CTCAE v.3, grade 1
- Patients who are pregnant or nursing
Sites / Locations
- Saint Joseph's Hospital and Medical Center
- Mayo Clinic in Arizona
- University of Arizona Cancer Center-North Campus
- Providence Saint Joseph Medical Center/Disney Family Cancer Center
- John Muir Medical Center-Concord Campus
- UC San Diego Moores Cancer Center
- UCLA / Jonsson Comprehensive Cancer Center
- Palo Alto Medical Foundation-Gynecologic Oncology
- UC San Diego Medical Center - Hillcrest
- San Diego VA Medical Center
- UCSF Medical Center-Mount Zion
- John Muir Medical Center-Walnut Creek
- UCHealth University of Colorado Hospital
- Rocky Mountain Gynecologic Oncology PC
- Hartford Hospital
- Smilow Cancer Hospital Care Center at Saint Francis
- The Hospital of Central Connecticut
- Yale University
- Beebe Medical Center
- Christiana Care Health System-Christiana Hospital
- MedStar Washington Hospital Center
- Morton Plant Hospital
- Mayo Clinic in Florida
- University of Miami Miller School of Medicine-Sylvester Cancer Center
- AdventHealth Orlando
- Orlando Health Cancer Institute
- Central Georgia Gynecologic Oncology
- Memorial Health University Medical Center
- Pali Momi Medical Center
- Hawaii Cancer Care Inc - Waterfront Plaza
- Queen's Medical Center
- Straub Clinic and Hospital
- University of Hawaii Cancer Center
- Queen's Cancer Center - Kuakini
- The Cancer Center of Hawaii-Liliha
- Kapiolani Medical Center for Women and Children
- Wilcox Memorial Hospital and Kauai Medical Clinic
- Maui Memorial Medical Center
- Pacific Cancer Institute of Maui
- Saint Alphonsus Cancer Care Center-Boise
- Northwestern University
- Rush University Medical Center
- University of Chicago Comprehensive Cancer Center
- Advocate Sherman Hospital
- Hinsdale Hematology Oncology Associates Incorporated
- Sudarshan K Sharma MD Limited-Gynecologic Oncology
- Elkhart Clinic
- Michiana Hematology Oncology PC-Elkhart
- Elkhart General Hospital
- Ascension Saint Vincent Indianapolis Hospital
- Community Howard Regional Health
- IU Health La Porte Hospital
- Michiana Hematology Oncology PC-Mishawaka
- Saint Joseph Regional Medical Center-Mishawaka
- Michiana Hematology Oncology PC-Plymouth
- Memorial Hospital of South Bend
- Michiana Hematology Oncology PC-South Bend
- South Bend Clinic
- Northern Indiana Cancer Research Consortium
- Michiana Hematology Oncology PC-Westville
- McFarland Clinic - Ames
- Medical Oncology and Hematology Associates-West Des Moines
- Mercy Cancer Center-West Lakes
- Iowa Methodist Medical Center
- Iowa-Wide Oncology Research Coalition NCORP
- Medical Oncology and Hematology Associates-Des Moines
- Mercy Medical Center - Des Moines
- Mission Cancer and Blood - Laurel
- Iowa Lutheran Hospital
- University of Iowa/Holden Comprehensive Cancer Center
- Methodist West Hospital
- Mercy Medical Center-West Lakes
- Cancer Center of Kansas - Chanute
- Cancer Center of Kansas - Dodge City
- Cancer Center of Kansas - El Dorado
- Cancer Center of Kansas - Fort Scott
- Cancer Center of Kansas-Independence
- University of Kansas Cancer Center
- Cancer Center of Kansas-Kingman
- Lawrence Memorial Hospital
- Cancer Center of Kansas-Liberal
- Cancer Center of Kansas - McPherson
- Cancer Center of Kansas - Newton
- Cancer Center of Kansas - Parsons
- Cancer Center of Kansas - Pratt
- Cancer Center of Kansas - Salina
- Cancer Center of Kansas - Wellington
- Associates In Womens Health
- Cancer Center of Kansas-Wichita Medical Arts Tower
- Ascension Via Christi Hospitals Wichita
- Cancer Center of Kansas - Wichita
- Wichita NCI Community Oncology Research Program
- Cancer Center of Kansas - Winfield
- Baptist Health Lexington
- University of Kentucky/Markey Cancer Center
- The James Graham Brown Cancer Center at University of Louisville
- Maine Medical Center-Bramhall Campus
- Greater Baltimore Medical Center
- Sinai Hospital of Baltimore
- MedStar Franklin Square Medical Center/Weinberg Cancer Institute
- Christiana Care - Union Hospital
- Baystate Medical Center
- UMass Memorial Medical Center - Memorial Division
- Michigan Cancer Research Consortium NCORP
- Saint Joseph Mercy Hospital
- Beaumont Hospital - Dearborn
- Ascension Saint John Hospital
- Hurley Medical Center
- Genesys Regional Medical Center-West Flint Campus
- Allegiance Health
- Bronson Methodist Hospital
- West Michigan Cancer Center
- Borgess Medical Center
- Sparrow Hospital
- Trinity Health Saint Mary Mercy Livonia Hospital
- Lakeland Hospital Niles
- Saint Joseph Mercy Oakland
- Lake Huron Medical Center
- William Beaumont Hospital-Royal Oak
- Ascension Saint Mary's Hospital
- Lakeland Medical Center Saint Joseph
- Marie Yeager Cancer Center
- Saint John Macomb-Oakland Hospital
- Mayo Clinic in Rochester
- Saint Dominic-Jackson Memorial Hospital
- University of Mississippi Medical Center
- Singing River Hospital
- MU Health - University Hospital/Ellis Fischel Cancer Center
- Delbert Day Cancer Institute at PCRMC
- SSM Health Saint Louis University Hospital
- Washington University School of Medicine
- Cancer Research for the Ozarks NCORP
- Mercy Hospital Springfield
- CoxHealth South Hospital
- Nebraska Methodist Hospital
- Women's Cancer Center of Nevada
- Center of Hope at Renown Medical Center
- Renown Regional Medical Center
- Cooper Hospital University Medical Center
- Morristown Medical Center
- Virtua Memorial
- Rutgers New Jersey Medical School
- Saint Luke's Hospital-Warren Campus
- Overlook Hospital
- Virtua Voorhees
- University of New Mexico Cancer Center
- Southwest Gynecologic Oncology Associates Inc
- Women's Cancer Care Associates LLC
- Island Gynecologic Oncology
- State University of New York Downstate Medical Center
- Roswell Park Cancer Institute
- New York Hospital Medical Center of Queens
- Memorial Sloan Kettering Cancer Center
- Stony Brook University Medical Center
- Hope Women's Cancer Centers-Asheville
- Cone Health Cancer Center at Alamance Regional
- Carolinas Medical Center/Levine Cancer Institute
- Novant Health Presbyterian Medical Center
- Duke University Medical Center
- Wake Forest University Health Sciences
- Summa Health System - Akron Campus
- Cleveland Clinic Akron General
- University of Cincinnati Cancer Center-UC Medical Center
- Case Western Reserve University
- MetroHealth Medical Center
- Cleveland Clinic Cancer Center/Fairview Hospital
- Cleveland Clinic Foundation
- Ohio State University Comprehensive Cancer Center
- Riverside Methodist Hospital
- Miami Valley Hospital
- Kettering Medical Center
- Hillcrest Hospital Cancer Center
- UH Seidman Cancer Center at Lake Health Mentor Campus
- University of Oklahoma Health Sciences Center
- Oklahoma Cancer Specialists and Research Institute-Tulsa
- Jefferson Abington Hospital
- Lehigh Valley Hospital-Cedar Crest
- Geisinger Medical Center
- Geisinger Medical Center-Cancer Center Hazleton
- Penn State Milton S Hershey Medical Center
- Pennsylvania Hospital
- Fox Chase Cancer Center
- Geisinger Medical Group
- Reading Hospital
- Geisinger Wyoming Valley/Henry Cancer Center
- Women and Infants Hospital
- Medical University of South Carolina
- South Carolina Oncology Associates PA
- Sanford Cancer Center Oncology Clinic
- Avera Cancer Institute
- Sanford USD Medical Center - Sioux Falls
- Vanderbilt University/Ingram Cancer Center
- Parkland Memorial Hospital
- Clements University Hospital
- UT Southwestern/Simmons Cancer Center-Dallas
- University of Texas Medical Branch
- Lyndon Baines Johnson General Hospital
- M D Anderson Cancer Center
- Scott and White Memorial Hospital
- University of Vermont Medical Center
- University of Virginia Cancer Center
- Virginia Oncology Associates-Hampton
- Virginia Oncology Associates - Lake Wright
- Virginia Commonwealth University/Massey Cancer Center
- Carilion Clinic Gynecological Oncology
- PeaceHealth Medical Group PC
- Harrison HealthPartners Hematology and Oncology-Bremerton
- Harrison Medical Center
- Providence Regional Cancer Partnership
- Skagit Regional Health Cancer Care Center
- Harrison HealthPartners Hematology and Oncology-Poulsbo
- Pacific Gynecology Specialists
- FHCC South Lake Union
- Fred Hutchinson Cancer Research Center
- Kaiser Permanente Washington
- Swedish Medical Center-First Hill
- University of Washington Medical Center - Northwest
- University of Washington Medical Center - Montlake
- Olympic Medical Cancer Care Center
- Cancer Care Northwest - Spokane South
- MultiCare Deaconess Cancer and Blood Specialty Center - Downtown
- MultiCare Tacoma General Hospital
- Saint Joseph Medical Center
- Providence Saint Mary Regional Cancer Center
- Wenatchee Valley Hospital and Clinics
- Gundersen Lutheran Medical Center
- University of Wisconsin Carbone Cancer Center
- Aurora Saint Luke's Medical Center
- Medical College of Wisconsin
- Aurora Sinai Medical Center
- Vince Lombardi Cancer Clinic - Oshkosh
- Vince Lombardi Cancer Clinic-Sheboygan
- Aurora West Allis Medical Center
Arms of the Study
Arm 1
Arm 2
Arm 3
Experimental
Experimental
Experimental
Arm I (paclitaxel, carboplatin, bevacizumab)
Arm II (paclitaxel, carboplatin, temsirolimus)
Arm III (ixabepilone, carboplatin, bevacizumab)
Patients receive paclitaxel IV over 3 hours, carboplatin IV over 30 minutes, and bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity.
Patients receive paclitaxel IV over 3 hours and carboplatin IV over 30 minutes on day 1 and temsirolimus IV over 30 minutes on days 1 and 8. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity.
Patients receive ixabepilone IV over 1 hour, carboplatin IV over 30 minutes, and bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity.