AKT-estäjän, ipatasertibin, lisäämisen testaus hormonaalisella lääkkeellä Megestroliasetaatilla toistuvien tai metastasoituneiden kohdun limakalvosyöpien varalta
Vaihe IB ja satunnaistettu vaihe II megestroliasetaatilla ipatasertibin kanssa tai ilman sitä uusiutuvassa tai metastasoituneessa endometrioidisyövässä
This phase Ib/II trial tests the safety, side effects, best dose, and effectiveness of the combination of ipatasertib with megestrol acetate to megestrol acetate alone in patients with endometrial cancer that has come back (recurrent) or has spread to other places in the body (metastatic). Ipatasertib may stop the growth of tumor cells and may kill them by blocking some of the enzymes needed for cell growth. Megestrol acetate lowers the amount of estrogen and also blocks the use of estrogen made by the body. This may help stop the growth of tumor cells that need estrogen to grow. The combination of ipatasertib and megestrol acetate may be more effective in treating endometrial cancer than megestrol acetate alone.
Tutkimuksen yleiskatsaus
Tila
Ehdot
Yksityiskohtainen kuvaus
PRIMARY OBJECTIVES:
I. Determine the toxicity of ipatasertib in combination with megestrol acetate in women with metastatic grade 1-2 endometrioid endometrial cancer and establish the recommended phase II dose. (Phase I) II. Compare the progression free survival of the combination of ipatasertib with megestrol acetate to megestrol acetate alone among women with metastatic grade 1-2 endometrioid adenocarcinoma of the endometrium. (Phase II) III. Compare the toxicity of the combination of ipatasertib with megestrol acetate to megestrol acetate alone. (Phase II)
SECONDARY OBJECTIVES:
I. Compare objective response rate per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 between the two arms.
II. Examine the pharmacokinetics of ipatasertib + megestrol acetate to assess potential drug-drug interactions.
III. Assess the association between biomarkers and response to therapy.
EXPLORATORY OBJECTIVE:
I. Explore whether pS6/total S6 and pPRAS40/total PRAS40 expression is impacted by the use of ipatasertib and megestrol acetate.
OUTLINE: This is a phase Ib, dose de-escalation study of ipatasertib followed by a phase II study.
PHASE Ib: Patients receive megestrol acetate orally (PO) once daily (QD) on days 1-28 and ipatasertib PO QD on days 1-21 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo a computed tomography (CT) or magnetic resonance imaging (MRI) during screening, on study, and during follow-up. Patients also undergo collection of blood samples throughout the trial.
PHASE II: Patients are randomized to 1 of 2 arms.
ARM I: Patients receive megestrol acetate PO QD on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo a CT or MRI during screening, on study, and during follow-up. Patients also undergo collection of blood samples throughout the trial.
ARM II: Patients receive megestrol acetate PO QD on days 1-28 and ipatasertib PO QD on days 1-21 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo a CT or MRI during screening, on study, and during follow-up. Patients also undergo collection of blood samples throughout the trial.
After completion of study treatment, patients are followed up at 30 days for the phase I study. Patients are followed up every 3 months for 2 years, then every 6 months for 3 years for the phase II study.
Opintotyyppi
Ilmoittautuminen (Arvioitu)
Vaihe
- Vaihe 2
- Vaihe 1
Yhteystiedot ja paikat
Opiskelupaikat
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Arizona
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Tucson, Arizona, Yhdysvallat, 85719
- Banner University Medical Center - Tucson
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Tucson, Arizona, Yhdysvallat, 85719
- University of Arizona Cancer Center-North Campus
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Arkansas
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Fayetteville, Arkansas, Yhdysvallat, 72703
- Highlands Oncology Group - Fayetteville
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Rogers, Arkansas, Yhdysvallat, 72758
- Highlands Oncology Group - Rogers
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Springdale, Arkansas, Yhdysvallat, 72762
- Highlands Oncology Group
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California
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Sacramento, California, Yhdysvallat, 95817
- University of California Davis Comprehensive Cancer Center
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Colorado
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Aurora, Colorado, Yhdysvallat, 80045
- UCHealth University of Colorado Hospital
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Florida
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Gainesville, Florida, Yhdysvallat, 32610
- UF Health Cancer Institute - Gainesville
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N. Venice, Florida, Yhdysvallat, 34275
- Sarasota Memorial Hospital-Venice
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Sarasota, Florida, Yhdysvallat, 34239
- Sarasota Memorial Hospital
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Sarasota, Florida, Yhdysvallat, 34239
- Florida Cancer Specialists - Sarasota Downtown
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Sarasota, Florida, Yhdysvallat, 34239
- FPG - Surgical Oncology Clinics Gynecologic Oncology Surgery
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Venice, Florida, Yhdysvallat, 34275
- Florida Cancer Specialists - Venice Pinebrook
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Georgia
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Augusta, Georgia, Yhdysvallat, 30912
- Augusta University Medical Center
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Idaho
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Boise, Idaho, Yhdysvallat, 83706
- Saint Alphonsus Cancer Care Center-Boise
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Boise, Idaho, Yhdysvallat, 83712
- Saint Luke's Cancer Institute - Boise
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Caldwell, Idaho, Yhdysvallat, 83605
- Saint Alphonsus Cancer Care Center-Caldwell
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Coeur d'Alene, Idaho, Yhdysvallat, 83814
- Kootenai Health - Coeur d'Alene
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Fruitland, Idaho, Yhdysvallat, 83619
- Saint Luke's Cancer Institute - Fruitland
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Meridian, Idaho, Yhdysvallat, 83642
- Saint Luke's Cancer Institute - Meridian
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Nampa, Idaho, Yhdysvallat, 83687
- Saint Alphonsus Cancer Care Center-Nampa
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Nampa, Idaho, Yhdysvallat, 83687
- Saint Luke's Cancer Institute - Nampa
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Post Falls, Idaho, Yhdysvallat, 83854
- Kootenai Clinic Cancer Services - Post Falls
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Sandpoint, Idaho, Yhdysvallat, 83864
- Kootenai Clinic Cancer Services - Sandpoint
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Illinois
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Chicago, Illinois, Yhdysvallat, 60611
- Northwestern University
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Chicago, Illinois, Yhdysvallat, 60612
- University of Illinois
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Danville, Illinois, Yhdysvallat, 61832
- Carle at The Riverfront
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DeKalb, Illinois, Yhdysvallat, 60115
- Northwestern Medicine Cancer Center Kishwaukee
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Decatur, Illinois, Yhdysvallat, 62526
- Decatur Memorial Hospital
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Decatur, Illinois, Yhdysvallat, 62526
- Cancer Care Specialists of Illinois - Decatur
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Effingham, Illinois, Yhdysvallat, 62401
- Crossroads Cancer Center
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Effingham, Illinois, Yhdysvallat, 62401
- Carle Physician Group-Effingham
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Geneva, Illinois, Yhdysvallat, 60134
- Northwestern Medicine Cancer Center Delnor
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Grayslake, Illinois, Yhdysvallat, 60030
- Northwestern Medicine Grayslake Outpatient Center
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Lake Forest, Illinois, Yhdysvallat, 60045
- Northwestern Medicine Lake Forest Hospital
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Mattoon, Illinois, Yhdysvallat, 61938
- Carle Physician Group-Mattoon/Charleston
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O'Fallon, Illinois, Yhdysvallat, 62269
- Cancer Care Center of O'Fallon
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Orland Park, Illinois, Yhdysvallat, 60462
- Northwestern Medicine Orland Park
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Springfield, Illinois, Yhdysvallat, 62702
- Southern Illinois University School of Medicine
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Springfield, Illinois, Yhdysvallat, 62702
- Springfield Clinic
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Springfield, Illinois, Yhdysvallat, 62781
- Springfield Memorial Hospital
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Urbana, Illinois, Yhdysvallat, 61801
- Carle Cancer Center
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Warrenville, Illinois, Yhdysvallat, 60555
- Northwestern Medicine Cancer Center Warrenville
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Indiana
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Carmel, Indiana, Yhdysvallat, 46032
- IU Health North Hospital
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Fort Wayne, Indiana, Yhdysvallat, 46845
- Parkview Regional Medical Center
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Goshen, Indiana, Yhdysvallat, 46526
- Goshen Center for Cancer Care
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Indianapolis, Indiana, Yhdysvallat, 46202
- Indiana University/Melvin and Bren Simon Cancer Center
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South Bend, Indiana, Yhdysvallat, 46601
- Memorial Hospital of South Bend
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Iowa
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Ankeny, Iowa, Yhdysvallat, 50023
- UI Health Care Mission Cancer and Blood - Ankeny Clinic
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Des Moines, Iowa, Yhdysvallat, 50309
- Iowa Methodist Medical Center
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Des Moines, Iowa, Yhdysvallat, 50309
- UI Health Care Mission Cancer and Blood - Des Moines Clinic
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Iowa City, Iowa, Yhdysvallat, 52242
- University of Iowa/Holden Comprehensive Cancer Center
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Kansas
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Kansas City, Kansas, Yhdysvallat, 66160
- University of Kansas Cancer Center
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Overland Park, Kansas, Yhdysvallat, 66211
- University of Kansas Hospital-Indian Creek Campus
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Westwood, Kansas, Yhdysvallat, 66205
- University of Kansas Hospital-Westwood Cancer Center
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Maine
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Augusta, Maine, Yhdysvallat, 04330
- Harold Alfond Center for Cancer Care
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Scarborough, Maine, Yhdysvallat, 04074
- MaineHealth Maine Medical Center- Scarborough
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Maryland
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Bethesda, Maryland, Yhdysvallat, 20889-5600
- Walter Reed National Military Medical Center
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Michigan
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Ann Arbor, Michigan, Yhdysvallat, 48109
- University of Michigan Rogel Cancer Center
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Battle Creek, Michigan, Yhdysvallat, 49017
- Bronson Battle Creek
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Grand Rapids, Michigan, Yhdysvallat, 49503
- Trinity Health Grand Rapids Hospital
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Grand Rapids, Michigan, Yhdysvallat, 49503
- Corewell Health Grand Rapids Hospitals - Butterworth Hospital
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Kalamazoo, Michigan, Yhdysvallat, 49007
- West Michigan Cancer Center
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Kalamazoo, Michigan, Yhdysvallat, 49007
- Bronson Methodist Hospital
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Kalamazoo, Michigan, Yhdysvallat, 49009
- Beacon Kalamazoo Cancer Center
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Muskegon, Michigan, Yhdysvallat, 49444
- Trinity Health Muskegon Hospital
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Niles, Michigan, Yhdysvallat, 49120
- Corewell Health Lakeland Hospitals - Niles Hospital
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Norton Shores, Michigan, Yhdysvallat, 49444
- Cancer and Hematology Centers of Western Michigan - Norton Shores
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Reed City, Michigan, Yhdysvallat, 49677
- Corewell Health Reed City Hospital
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Saint Joseph, Michigan, Yhdysvallat, 49085
- Corewell Health Lakeland Hospitals - Marie Yeager Cancer Center
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Saint Joseph, Michigan, Yhdysvallat, 49085
- Corewell Health Lakeland Hospitals - Saint Joseph Hospital
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Traverse City, Michigan, Yhdysvallat, 49684
- Munson Medical Center
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Wyoming, Michigan, Yhdysvallat, 49519
- University of Michigan Health - West
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Minnesota
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Coon Rapids, Minnesota, Yhdysvallat, 55433
- Mercy Hospital
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Edina, Minnesota, Yhdysvallat, 55435
- Fairview Southdale Hospital
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Minneapolis, Minnesota, Yhdysvallat, 55407
- Abbott-Northwestern Hospital
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Minneapolis, Minnesota, Yhdysvallat, 55455
- University of Minnesota/Masonic Cancer Center
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Saint Louis Park, Minnesota, Yhdysvallat, 55416
- Park Nicollet Clinic - Saint Louis Park
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Saint Paul, Minnesota, Yhdysvallat, 55101
- Regions Hospital
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Saint Paul, Minnesota, Yhdysvallat, 55102
- United Hospital
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Woodbury, Minnesota, Yhdysvallat, 55125
- Minnesota Oncology Hematology PA-Woodbury
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Missouri
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Columbia, Missouri, Yhdysvallat, 65212
- MU Health - University Hospital/Ellis Fischel Cancer Center
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Jefferson City, Missouri, Yhdysvallat, 65109
- MU Health Care Goldschmidt Cancer Center
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Kansas City, Missouri, Yhdysvallat, 64154
- University of Kansas Cancer Center - North
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Springfield, Missouri, Yhdysvallat, 65804
- Mercy Hospital Springfield
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St Louis, Missouri, Yhdysvallat, 63141
- Mercy Hospital Saint Louis
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St Louis, Missouri, Yhdysvallat, 63128
- Mercy Hospital South
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Montana
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Anaconda, Montana, Yhdysvallat, 59711
- Community Hospital of Anaconda
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Billings, Montana, Yhdysvallat, 59101
- Billings Clinic Cancer Center
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Bozeman, Montana, Yhdysvallat, 59715
- Bozeman Health Deaconess Hospital
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Great Falls, Montana, Yhdysvallat, 59405
- Benefis Sletten Cancer Institute
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Missoula, Montana, Yhdysvallat, 59804
- Community Medical Center
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New Jersey
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Camden, New Jersey, Yhdysvallat, 08103
- Cooper Hospital University Medical Center
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New Mexico
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Albuquerque, New Mexico, Yhdysvallat, 87106
- University of New Mexico Cancer Center
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New York
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Rochester, New York, Yhdysvallat, 14642
- University of Rochester
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Syracuse, New York, Yhdysvallat, 13210
- State University of New York Upstate Medical University
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The Bronx, New York, Yhdysvallat, 10461
- Montefiore Medical Center-Einstein Campus
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The Bronx, New York, Yhdysvallat, 10467
- Montefiore Medical Center - Moses Campus
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The Bronx, New York, Yhdysvallat, 10461
- Montefiore Medical Center-Weiler Hospital
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North Carolina
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Chapel Hill, North Carolina, Yhdysvallat, 27599
- UNC Lineberger Comprehensive Cancer Center
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Charlotte, North Carolina, Yhdysvallat, 28203
- Carolinas Medical Center/Levine Cancer Institute
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Concord, North Carolina, Yhdysvallat, 28025
- Atrium Health Cabarrus/LCI-Concord
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Ohio
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Akron, Ohio, Yhdysvallat, 44304
- Summa Health System - Akron Campus
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Beachwood, Ohio, Yhdysvallat, 44122
- UHHS-Chagrin Highlands Medical Center
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Centerville, Ohio, Yhdysvallat, 45459
- Miami Valley Hospital South
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Chardon, Ohio, Yhdysvallat, 44024
- Geauga Hospital
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Cincinnati, Ohio, Yhdysvallat, 45220
- Good Samaritan Hospital - Cincinnati
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Cleveland, Ohio, Yhdysvallat, 44106
- Case Western Reserve University
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Cleveland, Ohio, Yhdysvallat, 44195
- Cleveland Clinic Foundation
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Columbus, Ohio, Yhdysvallat, 43214
- Riverside Methodist Hospital
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Columbus, Ohio, Yhdysvallat, 43210
- Ohio State University Comprehensive Cancer Center
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Dayton, Ohio, Yhdysvallat, 45409
- Miami Valley Hospital
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Dayton, Ohio, Yhdysvallat, 45415
- Miami Valley Hospital North
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Franklin, Ohio, Yhdysvallat, 45005-1066
- Atrium Medical Center-Middletown Regional Hospital
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Greenville, Ohio, Yhdysvallat, 45331
- Miami Valley Cancer Care and Infusion
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Mentor, Ohio, Yhdysvallat, 44060
- UH Seidman Cancer Center at Lake Health Mentor Campus
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Troy, Ohio, Yhdysvallat, 45373
- Upper Valley Medical Center
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Westlake, Ohio, Yhdysvallat, 44145
- UH Seidman Cancer Center at Saint John Medical Center
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Oklahoma
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Oklahoma City, Oklahoma, Yhdysvallat, 73104
- University of Oklahoma Health Sciences Center
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Tulsa, Oklahoma, Yhdysvallat, 74146
- Oklahoma Cancer Specialists and Research Institute-Tulsa
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Oregon
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Ontario, Oregon, Yhdysvallat, 97914
- Saint Alphonsus Cancer Care Center-Ontario
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Portland, Oregon, Yhdysvallat, 97213
- Providence Portland Medical Center
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Portland, Oregon, Yhdysvallat, 97225
- Providence Saint Vincent Medical Center
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Pennsylvania
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Jefferson Hills, Pennsylvania, Yhdysvallat, 15025
- Jefferson Hospital
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Monroeville, Pennsylvania, Yhdysvallat, 15146
- Forbes Hospital
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Philadelphia, Pennsylvania, Yhdysvallat, 19107
- Thomas Jefferson University Hospital
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Pittsburgh, Pennsylvania, Yhdysvallat, 15212
- Allegheny General Hospital
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Pittsburgh, Pennsylvania, Yhdysvallat, 15224
- West Penn Hospital
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Wexford, Pennsylvania, Yhdysvallat, 15090
- Wexford Health and Wellness Pavilion
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Willow Grove, Pennsylvania, Yhdysvallat, 19090
- Asplundh Cancer Pavilion
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Rhode Island
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Providence, Rhode Island, Yhdysvallat, 02905
- Women and Infants Hospital
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South Carolina
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Charleston, South Carolina, Yhdysvallat, 29425
- Medical University of South Carolina
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Tennessee
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Nashville, Tennessee, Yhdysvallat, 37232
- Vanderbilt University/Ingram Cancer Center
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Texas
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Dallas, Texas, Yhdysvallat, 75235
- Parkland Memorial Hospital
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Dallas, Texas, Yhdysvallat, 75390
- UT Southwestern/Simmons Cancer Center-Dallas
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Fort Worth, Texas, Yhdysvallat, 76104
- UT Southwestern/Simmons Cancer Center-Fort Worth
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Houston, Texas, Yhdysvallat, 77026-1967
- Lyndon Baines Johnson General Hospital
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Houston, Texas, Yhdysvallat, 77030
- UT MD Anderson Cancer Center
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Houston, Texas, Yhdysvallat, 77030
- Memorial Hermann Texas Medical Center
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Richardson, Texas, Yhdysvallat, 75080
- UT Southwestern Clinical Center at Richardson/Plano
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Utah
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Salt Lake City, Utah, Yhdysvallat, 84112
- Huntsman Cancer Institute/University of Utah
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Virginia
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Charlottesville, Virginia, Yhdysvallat, 22908
- University of Virginia Cancer Center
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Richmond, Virginia, Yhdysvallat, 23235
- VCU Massey Cancer Center at Stony Point
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Richmond, Virginia, Yhdysvallat, 23298
- VCU Massey Comprehensive Cancer Center
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Roanoke, Virginia, Yhdysvallat, 24033
- Carilion Roanoke Memorial Hospital
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Washington
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Edmonds, Washington, Yhdysvallat, 98026
- Swedish Cancer Institute-Edmonds
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Issaquah, Washington, Yhdysvallat, 98029
- Swedish Cancer Institute-Issaquah
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Seattle, Washington, Yhdysvallat, 98122
- Swedish Medical Center-First Hill
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West Virginia
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Charleston, West Virginia, Yhdysvallat, 25304
- Vandalia Health/CAMC Institute for Academic Medicine
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Wisconsin
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Madison, Wisconsin, Yhdysvallat, 53792
- University of Wisconsin Carbone Cancer Center - University Hospital
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Madison, Wisconsin, Yhdysvallat, 53718
- University of Wisconsin Carbone Cancer Center - Eastpark Medical Center
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Milwaukee, Wisconsin, Yhdysvallat, 53226
- Medical College of Wisconsin
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Osallistumiskriteerit
Kelpoisuusvaatimukset
Opintokelpoiset iät
Hyväksyy terveitä vapaaehtoisia
Sukupuolet, jotka voivat opiskella
Kuvaus
Inclusion Criteria:
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Patients must have grade 1 or 2 recurrent or metastatic endometrioid endometrial cancer
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Patients must have measurable disease according to RECIST version (v)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 CT or MRI. Lymph nodes must be >= 15 mm in short axis when measured by CT or MRI. Previously irradiated lesions can be considered as measurable disease only if progressive disease has been unequivocally documented at that site since radiation
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Patients may have received unlimited prior lines of therapy. If patient received prior hormonal therapy (e.g., megestrol acetate, medroxyprogesterone acetate, aromatase inhibitor, tamoxifen, fulvestrant) it must have completed at least 6 months prior to registration
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Age >= 18
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Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1 or 2
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Platelets >= 100,000/mcl within 14 days prior to registration
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Absolute neutrophil count (ANC) >= 1,500/mcl within 14 days prior to registration
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Hemoglobin >= 9 g/dL within 14 days prior to registration
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Glomerular filtration rate (GFR) >= 60 mL/min/1.73m^2 measured using Cockcroft-Gault equation or the estimated glomerular filtration rate from the Modification of Diet in Renal Disease Study within 14 days prior to registration
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Total bilirubin =< 1.5 x the upper limit of normal (ULN) within 14 days prior to registration
- Patients with known Gilbert syndrome who have bilirubin =< 3 x ULN may be enrolled
-
Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 3 x institutional ULN within 14 days prior to registration
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Albumin >= 3 g/dL within 14 days prior to registration
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Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better
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The effects of ipatasertib on the developing human fetus are unknown. For this reason and because AKT inhibitor agents as well as other therapeutic agents used in this trial are known to be teratogenic, participants of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) during study therapy and for 28 days following the last dose of study therapy. Should a participant become pregnant or suspect pregnancy while participating in this study, they should inform their treating physician immediately
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Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
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For patients with known human immunodeficiency virus (HIV), hepatitis B virus (HBV), and/or hepatitis C virus (HCV) infection:
- HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months of registration are eligible for this trial
- Patients with evidence of chronic hepatitis B virus (HBV) infection must have an undetectable HBV viral load on suppressive therapy, if indicated
- Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
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Patients with treated brain metastases are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression
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Patients must be able to swallow and retain oral medications and not have gastrointestinal illnesses that would preclude absorption of megestrol acetate or ipatasertib as judged by the treating physician
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The patient or a legally authorized representative must provide study-specific informed consent prior to study entry and, for patients treated in the United States (U.S.), authorization permitting release of personal health information
Exclusion Criteria:
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Patients who have had prior treatment with an AKT inhibitor (Prior treatment with PI3K or mTOR inhibitors is allowed)
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Patients who have received treatment with strong CYP3A inhibitors or inducers within 14 days or 5 drug-elimination half-lives, whichever is longer, prior to study registration
- Because the lists of these agents are constantly changing, it is important to regularly consult a frequently-updated medical reference. 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
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Patients with diabetes either requiring insulin therapy or with a baseline fasting glucose > 160 mg/dL and/or high glycosylated hemoglobin A1c (HbA1c) (> 8), suggesting poorly controlled diabetes. Fasting is defined as abstaining from food and drink (with the exception of water) for at least 8 hours
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Patients who require chronic corticosteroid therapy of > 10 mg of prednisone per day or an equivalent dose of other anti-inflammatory corticosteroids or immunosuppressant agents for a chronic disease
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Patients with grade 2 or greater uncontrolled or untreated hypercholesterolemia (> 300 mg/dL) or hypertriglyceridemia (> 300 mg/dL)
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Patients with a history of known or active inflammatory bowel disease (e.g., Crohn disease and ulcerative colitis) or active bowel inflammation (e.g., diverticulitis)
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Patients with a history of or presence of an abnormal electrocardiogram (ECG) that is clinically significant in the investigator's opinion (including complete left bundle branch block, second- or third-degree heart block, or evidence of prior myocardial infarction)
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Patients with known clinically significant history of liver disease consistent with Child-Pugh class B or C, including active viral or other hepatitis, current drug or alcohol abuse, or cirrhosis
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Patients with lung disease: Grade 2 or greater pneumonitis, grade 2 or greater interstitial lung disease, idiopathic pulmonary fibrosis, cystic fibrosis, aspergillosis, active tuberculosis, or history of opportunistic infections (pneumocystis pneumonia or cytomegalovirus pneumonia) within the past 6 months
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No active infection requiring parenteral antibiotics
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Women who are pregnant or unwilling to discontinue nursing
Opintosuunnitelma
Miten tutkimus on suunniteltu?
Suunnittelun yksityiskohdat
- Ensisijainen käyttötarkoitus: Hoito
- Jako: Satunnaistettu
- Inventiomalli: Rinnakkaistehtävä
- Naamiointi: Ei mitään (avoin tarra)
Aseet ja interventiot
Osallistujaryhmä / Arm |
Interventio / Hoito |
|---|---|
|
Kokeellinen: Phase Ib (megestrol acetate, ipatasertib)
Patients receive megestrol acetate PO QD on days 1-28 and ipatasertib PO QD on days 1-21 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo a CT or MRI during screening, on study, and during follow-up. Patients also undergo collection of blood samples throughout the trial. |
Undergo blood sample collection
Muut nimet:
Undergo MRI
Muut nimet:
Undergo CT scan
Muut nimet:
Given PO
Muut nimet:
Given PO
Muut nimet:
|
|
Active Comparator: Phase II (megestrol acetate)
Arm I: Patients receive megestrol acetate PO QD on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo a CT or MRI during screening, on study, and during follow-up. Patients also undergo collection of blood samples throughout the trial. |
Undergo blood sample collection
Muut nimet:
Undergo MRI
Muut nimet:
Undergo CT scan
Muut nimet:
Given PO
Muut nimet:
|
|
Kokeellinen: Phase II (megestrol acetate, ipatasertib)
Arm II: Patients receive megestrol acetate PO QD on days 1-28 and ipatasertib PO QD on days 1-21 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo a CT or MRI during screening, on study, and during follow-up. Patients also undergo collection of blood samples throughout the trial. |
Undergo blood sample collection
Muut nimet:
Undergo MRI
Muut nimet:
Undergo CT scan
Muut nimet:
Given PO
Muut nimet:
Given PO
Muut nimet:
|
Mitä tutkimuksessa mitataan?
Ensisijaiset tulostoimenpiteet
Tulosmittaus |
Toimenpiteen kuvaus |
Aikaikkuna |
|---|---|---|
|
Incidence of adverse events (AEs) (Phase Ib)
Aikaikkuna: Up to 5 years
|
To determine frequency and severity of adverse events for all dose combinations of megestrol acetate plus ipatasertib. Descriptive statistics will be used to summarize AEs. These analyses will focus on individuals who initiated their assigned treatment and will summarize maximum grade of AEs occurring during treatment classified by Common Toxicity Criteria (CTC) category. The primary summary of AEs will present counts and percentages, regardless of whether the AE was attributed to any of the study agents. |
Up to 5 years
|
|
Maximum tolerated dose for phase II (Phase Ib)
Aikaikkuna: Up to 5 years
|
Descriptive statistics will be used to summarize AEs. These analyses will focus on individuals who initiated their assigned treatment and will summarize maximum grade of AEs occurring during treatment classified by CTC category. The primary summary of AEs will present counts and percentages, regardless of whether the AE was attributed to any of the study agents. |
Up to 5 years
|
|
Progression free survival (PFS) (Phase II)
Aikaikkuna: From study entry to time of progression or death, whichever occurs first, or date of last contact if neither progression nor death has occurred, assessed up to 5 years
|
Compare PFS of the combination of ipatasertib with megestrol acetate to megestrol acetate alone among women with recurrent/metastatic endometrioid adenocarcinoma of the endometrium. A product-limit method will be used to estimate the cumulative distribution of PFS duration for each of the study treatments used in this population. |
From study entry to time of progression or death, whichever occurs first, or date of last contact if neither progression nor death has occurred, assessed up to 5 years
|
|
Incidence of AEs (Phase II)
Aikaikkuna: Up to 5 years
|
Summarize the toxicity/adverse events of the combination of ipatasertib with megestrol acetate and megestrol acetate alone. Adverse events will be categorized using Common Terminology Criteria for Adverse Events version 5.0. |
Up to 5 years
|
Toissijaiset tulostoimenpiteet
Tulosmittaus |
Toimenpiteen kuvaus |
Aikaikkuna |
|---|---|---|
|
Pharmacokinetics of ipatasertib + megestrol acetate (Phase Ib)
Aikaikkuna: On cycle 1, day 8
|
Examine the pharmacokinetics of ipatasertib + megestrol acetate to assess potential drug-drug interactions. This data will be summarized descriptively. |
On cycle 1, day 8
|
|
Objective response rate (Phase II)
Aikaikkuna: Up to 5 years
|
Response is defined as complete response or partial response (CR+PR) evaluated by Response Evaluation Criteria in Solid Tumors version 1.1. A logistic model will be used to estimate the relative odds of responding (CR+PR) to megestrol acetate + ipatasertib relative to megestrol acetate alone after adjusting for prior progesterone therapy. |
Up to 5 years
|
|
Biomarkers (Phase II)
Aikaikkuna: Up to 5 years
|
The association between biomarkers and response to therapy will be assessed. Integrated biomarker endpoints include: PTEN immunohistochemistry, estrogen receptor and progesterone receptor, whole exome sequencing, ribonucleic acid sequencing. Proportional hazards models will be used to examine the prognostic association of integrated biomarkers with PFS; and interactions between markers and treatment arm will be used to examine the markers' predictive association with PFS. |
Up to 5 years
|
Muut tulostoimenpiteet
Tulosmittaus |
Toimenpiteen kuvaus |
Aikaikkuna |
|---|---|---|
|
pS6/total S6 and pPRAS40/total PRAS40 expression (Phase II)
Aikaikkuna: Up to 5 years
|
Exploratory objectives include assessing whether pS6/total S6 and pPRAS40/total PRAS40 expression is impacted by the use of ipatasertib and megestrol acetate. Exploratory biomarker results will be provided to the NRG Oncology Statistical and Data Management Center for analysis. |
Up to 5 years
|
Yhteistyökumppanit ja tutkijat
Sponsori
Yhteistyökumppanit
Tutkijat
- Päätutkija: Michaela O Grinsfelder, NRG Oncology
Opintojen ennätyspäivät
Opi tärkeimmät päivämäärät
Opiskelun aloitus (Todellinen)
Ensisijainen valmistuminen (Arvioitu)
Opintojen valmistuminen (Arvioitu)
Opintoihin ilmoittautumispäivät
Ensimmäinen lähetetty
Ensimmäinen toimitettu, joka täytti QC-kriteerit
Ensimmäinen Lähetetty (Todellinen)
Tutkimustietojen päivitykset
Viimeisin päivitys julkaistu (Todellinen)
Viimeisin lähetetty päivitys, joka täytti QC-kriteerit
Viimeksi vahvistettu
Lisää tietoa
Tähän tutkimukseen liittyvät termit
Muita asiaankuuluvia MeSH-ehtoja
- Tutkintatekniikat
- Kliiniset laboratoriotekniikat
- Diagnostiikkatekniikat ja menettelyt
- Diagnoosi
- Polisykliset yhdisteet
- Raskaat
- Raskaat
- Steroidit
- Sulatettu rengasyhdisteet
- Kemian tekniikat, analyyttiset
- Spektrianalyysi
- Megestrol
- Megestroliasetaatti
- Näytteenkäsittely
- Magneettiresonanssispektroskopia
- ipaSertibi
Muut tutkimustunnusnumerot
- NCI-2022-07505
- U10CA180868 (Yhdysvaltain NIH-apuraha/sopimus)
- NCI-2022-07505 (Rekisterin tunniste: CTRP (Clinical Trial Reporting Program))
- NRG-GY028 (Muu tunniste: CTEP)
- NRG-GY028 (Muu tunniste: NRG Oncology)
Yksittäisten osallistujien tietojen suunnitelma (IPD)
Aiotko jakaa yksittäisten osallistujien tietoja (IPD)?
IPD-suunnitelman kuvaus
NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.
Lääke- ja laitetiedot, tutkimusasiakirjat
Tutkii yhdysvaltalaista FDA sääntelemää lääkevalmistetta
Tutkii yhdysvaltalaista FDA sääntelemää laitetuotetta
Yhdysvalloissa valmistettu ja sieltä viety tuote
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