Testování olaparibu a temozolomidu versus obvyklá léčba děložního leiomyosarkomu poté, co chemoterapie přestala fungovat
Randomizovaná studie fáze 2/3 Olaparib plus temozolomid versus volba výzkumníka pro léčbu pacientek s pokročilým děložním leiomyosarkomem po progresi předchozí chemoterapie
This phase II/III trial compares the effect of the combination treatment with olaparib and temozolomide to trabectedin or pazopanib (two of the most common chemotherapy drugs used as usual approach) in patients with uterine leiomyosarcoma that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced) after initial chemotherapy has stopped working. The usual approach is defined as care most people get for advanced uterine leiomyosarcoma. Olaparib is a PARP inhibitor. PARP is a protein that helps repair damaged deoxyribonucleic acid (DNA). Blocking PARP may prevent tumor cells from repairing their damaged DNA, causing them to die. PARP inhibitors are a type of targeted therapy. Temozolomide is in a class of medications called alkylating agents. It works by slowing or stopping the growth of tumor cells in the body. The combination of olaparib and temozolomide may work better than the usual treatment in shrinking or stabilizing advanced uterine leiomyosarcoma after initial chemotherapy has stopped working.
Přehled studie
Postavení
Postavení
Podmínky
Podmínky
Intervence / Léčba
Intervence / Léčba
Detailní popis
PRIMARY OBJECTIVES:
I. To compare the progression free survival (PFS) of olaparib plus temozolomide (Arm 1) as compared to investigator's choice (trabectedin or pazopanib hydrochloride [pazopanib]) (Arm 2) for the treatment of patients with advanced uterine leiomyosarcoma (uLMS) who have received two or more prior lines of therapy as determined by investigator (local site) assessment. (Phase 2) II. To compare the overall survival (OS) of olaparib plus temozolomide (Arm 1) as compared to investigator's choice (trabectedin or pazopanib) (Arm 2) for the treatment of patients with advanced uLMS who have received two or more prior lines of therapy. (Phase 3)
SECONDARY OBJECTIVES:
I. To evaluate the safety and tolerability of each treatment by determining adverse events using Common Terminology Criteria for Adverse Events (CTCAE) version 5 and patient-reported toxicity using Patient-Reported Outcome (PRO)-CTCAE version 1 in and across each treatment arm. (Phase 2/3) II. To evaluate the objective response rate (ORR), duration of response (DOR) and disease control rate (DCR) in and across each treatment arm as determined by investigator assessment. (Phase 2/3)
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM 1: Patients receive temozolomide orally (PO) once daily (QD) on days 1-7 of each cycle and olaparib PO twice daily (BID) on days 1-7 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients undergo computed tomography (CT) scan or magnetic resonance imaging (MRI) and/or bone scans throughout the trial. Patients also undergo collection of blood samples throughout the trial.
ARM 2: Patients receive trabectedin intravenously (IV) continuously over 24 hours on day 1 of each cycle or pazopanib PO QD on days 1-21 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan or MRI and/or bone scans throughout the trial. Patients also undergo transthoracic echocardiography (TTE) or multi-gated acquisition scan (MUGA) on study and as clinically indicated, as well as collection of blood samples throughout the trial.
After completion of study treatment, patients without disease progression are followed every 6 weeks until disease progression. After disease progression, patients are followed every 3 months for the first 2 years, then every 6 months thereafter until 5 years post-randomization or death, whichever comes first.
Typ studie
Typ studie
Zápis (Aktuální)
Zápis
Fáze
Fáze
- Fáze 2
- Fáze 3
Kontakty a umístění
Studijní místa
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San Juan, Portoriko, 00927
- Centro Comprensivo de Cancer de UPR
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Alabama
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Birmingham, Alabama, Spojené státy, 35233
- University of Alabama at Birmingham Cancer Center
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Alaska
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Anchorage, Alaska, Spojené státy, 99508
- Alaska Women's Cancer Care
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Arizona
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Phoenix, Arizona, Spojené státy, 85054
- Mayo Clinic Hospital in Arizona
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California
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Duarte, California, Spojené státy, 91010
- City of Hope Comprehensive Cancer Center
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Dublin, California, Spojené státy, 94568
- Epic Care-Dublin
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Emeryville, California, Spojené státy, 94608
- Epic Care Partners in Cancer Care
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Irvine, California, Spojené státy, 92618
- City of Hope at Irvine Lennar
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Martinez, California, Spojené státy, 94553-3156
- Contra Costa Regional Medical Center
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Walnut Creek, California, Spojené státy, 94597
- Epic Care Cyberknife Center
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Colorado
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Aurora, Colorado, Spojené státy, 80045
- UCHealth University of Colorado Hospital
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Colorado Springs, Colorado, Spojené státy, 80909
- UCHealth Memorial Hospital Central
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Colorado Springs, Colorado, Spojené státy, 80920
- Memorial Hospital North
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Fort Collins, Colorado, Spojené státy, 80524
- Poudre Valley Hospital
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Fort Collins, Colorado, Spojené státy, 80528
- Cancer Care and Hematology-Fort Collins
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Greeley, Colorado, Spojené státy, 80631
- UCHealth Greeley Hospital
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Loveland, Colorado, Spojené státy, 80538
- Medical Center of the Rockies
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Connecticut
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Derby, Connecticut, Spojené státy, 06418
- Smilow Cancer Hospital-Derby Care Center
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Fairfield, Connecticut, Spojené státy, 06824
- Smilow Cancer Hospital Care Center-Fairfield
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Glastonbury, Connecticut, Spojené státy, 06033
- Smilow Cancer Hospital Care Center at Glastonbury
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Greenwich, Connecticut, Spojené státy, 06830
- Smilow Cancer Hospital Care Center at Greenwich
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Guilford, Connecticut, Spojené státy, 06437
- Smilow Cancer Hospital Care Center - Guilford
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Hartford, Connecticut, Spojené státy, 06105
- Smilow Cancer Hospital Care Center at Saint Francis
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New Haven, Connecticut, Spojené státy, 06520
- Yale University
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North Haven, Connecticut, Spojené státy, 06473
- Yale-New Haven Hospital North Haven Medical Center
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Stamford, Connecticut, Spojené státy, 06902
- Smilow Cancer Hospital Care Center at Long Ridge
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Torrington, Connecticut, Spojené státy, 06790
- Smilow Cancer Hospital-Torrington Care Center
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Trumbull, Connecticut, Spojené státy, 06611
- Smilow Cancer Hospital Care Center-Trumbull
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Waterbury, Connecticut, Spojené státy, 06708
- Smilow Cancer Hospital-Waterbury Care Center
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Waterford, Connecticut, Spojené státy, 06385
- Smilow Cancer Hospital Care Center - Waterford
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District of Columbia
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Washington D.C., District of Columbia, Spojené státy, 20010
- MedStar Washington Hospital Center
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Florida
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Deerfield Beach, Florida, Spojené státy, 33442
- UM Sylvester Comprehensive Cancer Center at Deerfield Beach
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Jacksonville, Florida, Spojené státy, 32224-9980
- Mayo Clinic in Florida
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Miami, Florida, Spojené státy, 33136
- University of Miami Miller School of Medicine-Sylvester Cancer Center
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Plantation, Florida, Spojené státy, 33324
- UM Sylvester Comprehensive Cancer Center at Plantation
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Georgia
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Savannah, Georgia, Spojené státy, 31405
- Lewis Cancer and Research Pavilion at Saint Joseph's/Candler
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Idaho
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Boise, Idaho, Spojené státy, 83712
- Saint Luke's Cancer Institute - Boise
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Fruitland, Idaho, Spojené státy, 83619
- Saint Luke's Cancer Institute - Fruitland
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Meridian, Idaho, Spojené státy, 83642
- Saint Luke's Cancer Institute - Meridian
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Nampa, Idaho, Spojené státy, 83687
- Saint Luke's Cancer Institute - Nampa
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Twin Falls, Idaho, Spojené státy, 83301
- Saint Luke's Cancer Institute - Twin Falls
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Illinois
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Chicago, Illinois, Spojené státy, 60611
- Northwestern University
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Chicago, Illinois, Spojené státy, 60612
- University of Illinois
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Danville, Illinois, Spojené státy, 61832
- Carle at The Riverfront
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DeKalb, Illinois, Spojené státy, 60115
- Northwestern Medicine Cancer Center Kishwaukee
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Effingham, Illinois, Spojené státy, 62401
- Carle Physician Group-Effingham
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Evanston, Illinois, Spojené státy, 60201
- NorthShore University HealthSystem-Evanston Hospital
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Geneva, Illinois, Spojené státy, 60134
- Northwestern Medicine Cancer Center Delnor
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Glenview, Illinois, Spojené státy, 60026
- NorthShore University HealthSystem-Glenbrook Hospital
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Highland Park, Illinois, Spojené státy, 60035
- NorthShore University HealthSystem-Highland Park Hospital
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Lake Forest, Illinois, Spojené státy, 60045
- Northwestern Medicine Lake Forest Hospital
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Mattoon, Illinois, Spojené státy, 61938
- Carle Physician Group-Mattoon/Charleston
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Urbana, Illinois, Spojené státy, 61801
- Carle Cancer Center
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Warrenville, Illinois, Spojené státy, 60555
- Northwestern Medicine Cancer Center Warrenville
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Iowa
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Ames, Iowa, Spojené státy, 50010
- Mary Greeley Medical Center
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Ames, Iowa, Spojené státy, 50010
- McFarland Clinic - Ames
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Boone, Iowa, Spojené státy, 50036
- McFarland Clinic - Boone
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Council Bluffs, Iowa, Spojené státy, 51503
- Heartland Oncology and Hematology LLP
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Des Moines, Iowa, Spojené státy, 50314
- Mercy Medical Center - Des Moines
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Fort Dodge, Iowa, Spojené státy, 50501
- McFarland Clinic - Trinity Cancer Center
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Iowa City, Iowa, Spojené státy, 52242
- University of Iowa/Holden Comprehensive Cancer Center
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Jefferson, Iowa, Spojené státy, 50129
- McFarland Clinic - Jefferson
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Marshalltown, Iowa, Spojené státy, 50158
- McFarland Clinic - Marshalltown
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Kentucky
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Lexington, Kentucky, Spojené státy, 40503
- Baptist Health Lexington
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Louisiana
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Baton Rouge, Louisiana, Spojené státy, 70817
- Our Lady of the Lake Medical Oncology
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New Orleans, Louisiana, Spojené státy, 70112
- University Medical Center New Orleans
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Maine
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Scarborough, Maine, Spojené státy, 04074
- MaineHealth Maine Medical Center- Scarborough
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Massachusetts
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Boston, Massachusetts, Spojené státy, 02215
- Dana-Farber Cancer Institute
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Michigan
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Ann Arbor, Michigan, Spojené státy, 48109
- University of Michigan Rogel Cancer Center
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Battle Creek, Michigan, Spojené státy, 49017
- Bronson Battle Creek
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Grand Rapids, Michigan, Spojené státy, 49503
- Trinity Health Grand Rapids Hospital
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Grand Rapids, Michigan, Spojené státy, 49503
- Corewell Health Grand Rapids Hospitals - Butterworth Hospital
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Kalamazoo, Michigan, Spojené státy, 49007
- West Michigan Cancer Center
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Kalamazoo, Michigan, Spojené státy, 49007
- Bronson Methodist Hospital
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Kalamazoo, Michigan, Spojené státy, 49009
- Beacon Kalamazoo Cancer Center
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Muskegon, Michigan, Spojené státy, 49444
- Trinity Health Muskegon Hospital
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Norton Shores, Michigan, Spojené státy, 49444
- Cancer and Hematology Centers of Western Michigan - Norton Shores
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Reed City, Michigan, Spojené státy, 49677
- Corewell Health Reed City Hospital
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Saint Joseph, Michigan, Spojené státy, 49085
- Corewell Health Lakeland Hospitals - Marie Yeager Cancer Center
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Traverse City, Michigan, Spojené státy, 49684
- Munson Medical Center
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Wyoming, Michigan, Spojené státy, 49519
- University of Michigan Health - West
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Minnesota
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Coon Rapids, Minnesota, Spojené státy, 55433
- Mercy Hospital
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Edina, Minnesota, Spojené státy, 55435
- Fairview Southdale Hospital
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Minneapolis, Minnesota, Spojené státy, 55407
- Abbott-Northwestern Hospital
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Rochester, Minnesota, Spojené státy, 55905
- Mayo Clinic in Rochester
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Saint Louis Park, Minnesota, Spojené státy, 55416
- Park Nicollet Clinic - Saint Louis Park
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Saint Paul, Minnesota, Spojené státy, 55101
- Regions Hospital
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Saint Paul, Minnesota, Spojené státy, 55102
- United Hospital
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Missouri
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Creve Coeur, Missouri, Spojené státy, 63141
- Siteman Cancer Center at West County Hospital
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St Louis, Missouri, Spojené státy, 63110
- Washington University School of Medicine
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St Louis, Missouri, Spojené státy, 63129
- Siteman Cancer Center-South County
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St Louis, Missouri, Spojené státy, 63141
- Mercy Hospital Saint Louis
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Nebraska
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Omaha, Nebraska, Spojené státy, 68114
- Nebraska Methodist Hospital
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Omaha, Nebraska, Spojené státy, 68114
- Oncology Associates PC
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Omaha, Nebraska, Spojené státy, 68114
- Nebraska Cancer Specialists/Oncology Hematology West PC - MECC
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New Jersey
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Basking Ridge, New Jersey, Spojené státy, 07920
- Memorial Sloan Kettering Basking Ridge
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Middletown, New Jersey, Spojené státy, 07748
- Memorial Sloan Kettering Monmouth
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Montvale, New Jersey, Spojené státy, 07645
- Memorial Sloan Kettering Bergen
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New York
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Buffalo, New York, Spojené státy, 14263
- Roswell Park Cancer Institute
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Commack, New York, Spojené státy, 11725
- Memorial Sloan Kettering Commack
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Harrison, New York, Spojené státy, 10604
- Memorial Sloan Kettering Westchester
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Lake Success, New York, Spojené státy, 11042
- Northwell Health/Center for Advanced Medicine
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New York, New York, Spojené státy, 10065
- Memorial Sloan Kettering Cancer Center
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Uniondale, New York, Spojené státy, 11553
- Memorial Sloan Kettering Nassau
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North Carolina
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Chapel Hill, North Carolina, Spojené státy, 27599
- UNC Lineberger Comprehensive Cancer Center
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Durham, North Carolina, Spojené státy, 27710
- Duke University Medical Center
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Greenville, North Carolina, Spojené státy, 27834
- ECU Health Medical Center
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Ohio
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Avon, Ohio, Spojené státy, 44011
- UH Seidman Cancer Center at UH Avon Health Center
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Beachwood, Ohio, Spojené státy, 44122
- UHHS-Chagrin Highlands Medical Center
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Cleveland, Ohio, Spojené státy, 44106
- Case Western Reserve University
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Cleveland, Ohio, Spojené státy, 44195
- Cleveland Clinic Foundation
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Cleveland, Ohio, Spojené státy, 44111
- Cleveland Clinic Cancer Center/Fairview Hospital
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Mayfield Heights, Ohio, Spojené státy, 44124
- Hillcrest Hospital Cancer Center
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Oklahoma
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Oklahoma City, Oklahoma, Spojené státy, 73104
- University of Oklahoma Health Sciences Center
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Oregon
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Clackamas, Oregon, Spojené státy, 97015
- Clackamas Radiation Oncology Center
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Gresham, Oregon, Spojené státy, 97030
- Legacy Mount Hood Medical Center
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Newberg, Oregon, Spojené státy, 97132
- Providence Newberg Medical Center
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Oregon City, Oregon, Spojené státy, 97045
- Providence Willamette Falls Medical Center
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Portland, Oregon, Spojené státy, 97239
- Oregon Health and Science University
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Portland, Oregon, Spojené státy, 97210
- Legacy Good Samaritan Hospital and Medical Center
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Portland, Oregon, Spojené státy, 97213
- Providence Portland Medical Center
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Portland, Oregon, Spojené státy, 97225
- Providence Saint Vincent Medical Center
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Tualatin, Oregon, Spojené státy, 97062
- Legacy Meridian Park Hospital
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Pennsylvania
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Philadelphia, Pennsylvania, Spojené státy, 19111
- Fox Chase Cancer Center
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Philadelphia, Pennsylvania, Spojené státy, 19107
- Thomas Jefferson University Hospital
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Willow Grove, Pennsylvania, Spojené státy, 19090
- Asplundh Cancer Pavilion
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Rhode Island
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Providence, Rhode Island, Spojené státy, 02905
- Women and Infants Hospital
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Westerly, Rhode Island, Spojené státy, 02891
- Smilow Cancer Hospital Care Center - Westerly
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South Carolina
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Bluffton, South Carolina, Spojené státy, 29910
- Saint Joseph's/Candler - Bluffton Campus
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Charleston, South Carolina, Spojené státy, 29425
- Medical University of South Carolina
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Tennessee
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Nashville, Tennessee, Spojené státy, 37232
- Vanderbilt University/Ingram Cancer Center
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Virginia
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Richmond, Virginia, Spojené státy, 23235
- VCU Massey Cancer Center at Stony Point
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Richmond, Virginia, Spojené státy, 23298
- VCU Massey Comprehensive Cancer Center
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Washington
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Seattle, Washington, Spojené státy, 98195
- University of Washington Medical Center - Montlake
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Seattle, Washington, Spojené státy, 98109
- Fred Hutchinson Cancer Center
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Vancouver, Washington, Spojené státy, 98686
- Legacy Salmon Creek Hospital
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Vancouver, Washington, Spojené státy, 98684
- Legacy Cancer Institute Medical Oncology and Day Treatment
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West Virginia
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Charleston, West Virginia, Spojené státy, 25304
- Vandalia Health/CAMC Institute for Academic Medicine
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Wisconsin
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Eau Claire, Wisconsin, Spojené státy, 54701
- Marshfield Medical Center-EC Cancer Center
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Marshfield, Wisconsin, Spojené státy, 54449
- Marshfield Medical Center-Marshfield
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Milwaukee, Wisconsin, Spojené státy, 53226
- Medical College of Wisconsin
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Minocqua, Wisconsin, Spojené státy, 54548
- Marshfield Medical Center - Minocqua
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Rice Lake, Wisconsin, Spojené státy, 54868
- Marshfield Medical Center-Rice Lake
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Stevens Point, Wisconsin, Spojené státy, 54482
- Marshfield Medical Center-River Region at Stevens Point
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Weston, Wisconsin, Spojené státy, 54476
- Marshfield Medical Center - Weston
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Kritéria účasti
Kritéria způsobilosti
Kritéria způsobilosti
Věk způsobilý ke studiu
Přijímá zdravé dobrovolníky
Pohlaví způsobilá ke studiu
Popis
Inclusion Criteria:
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Histologically confirmed leiomyosarcoma of uterine origin, as established by the site institutional practice for pathology confirmation for research studies when enrolling the patient on study. Central pathology review will not occur.
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Metastatic or locally advanced and surgically unresectable disease, in the opinion of the treating investigator.
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Patients must have at least one lesion that is measurable per Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1 criteria to be eligible for the study.
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Not pregnant and not nursing, because this study involves agents that have known genotoxic, mutagenic and teratogenic effects. Therefore, for women of childbearing potential only, a negative pregnancy test done =< 7 days prior to registration is required
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Age >= 18 years.
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Eastern Cooperative Oncology Group (ECOG) Performance Status =< 2.
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Patients must have had prior progression on, or intolerance to, at least two prior lines of systemic therapy for advanced uLMS, one of which was an anthracycline (anthracycline monotherapy or combination). Adjuvant chemotherapy will qualify as a prior line of treatment. Endocrine treatment will not qualify as a prior line of treatment.
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Patients may not have received prior treatment with any PARP inhibitor, temozolomide or dacarbazine (IV analogue of temozolomide).
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Patients may not have had prior treatment with BOTH of the agents included on the investigator's choice arm: trabectedin AND pazopanib. If the patient has had prior treatment with one of these agents, they are eligible; however, they must be assigned to the other agent for investigator's choice. That is, patients who have received prior pazopanib must be assigned to trabectedin, and patients who have received prior trabectedin must be assigned to pazopanib.
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Patients must have recovered to baseline or =< grade 1 per CTCAE version 5.0 from toxicity related to any prior treatment, unless adverse events are clinically nonsignificant and/or stable on supportive therapy, with the exception of fatigue (which must be =< grade 2), alopecia and/or endocrinopathies related to prior immunotherapy which are controlled with hormone replacement.
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Patients must have completed all prior anti-cancer treatment, including radiation, >= 28 days prior to registration.
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Patients may have undergone major surgery (related or unrelated to their cancer diagnosis) >= 28 days of registration. Subjects with clinically relevant ongoing complications from prior surgery are not eligible.
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Absolute neutrophil count (ANC) >= 1500/mm^3 (within =< 28 days prior to registration).
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Platelet count >= 100,000/mm^3 (within =< 28 days prior to registration).
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Creatinine =< 1.5 * upper limit of normal (ULN) (within =< 28 days prior to registration).
- If creatinine > 1.5 * ULN, then creatinine clearance (CrCl) must be > 50 mL/min, per Cockcroft-Gault method.
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Hemoglobin >= 9 g/dL (within =< 28 days prior to registration).
- No transfusions =< 14 days before cycle 1 day 1 (C1D1).
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Total bilirubin =< 1.5 x ULN (within =< 28 days prior to registration).
- If documented Gilbert's: =< 2.0 x ULN.
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Aspartate aminotransferase/alanine aminotransferase (AST/ALT) =< 3 x ULN (within =< 28 days prior to registration).
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Patients may not have uncontrolled hypertension defined as a blood pressure (BP) > 150/90 on two consecutive assessments during the screening period. If a patient is found to have a BP > 150/90 on two consecutive assessments during the screening period, the patient may be started on an anti-hypertensive regimen, and will be considered eligible if two subsequent measurements are performed and the BP is =< 150/90. If BP is in range on the first measurement, no further measurements are needed.
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Patients must demonstrate a QTcF (Fredericia formula) =< 470 msec on an electrocardiography (EKG) performed during screening. This criterion applies only to patients who will receive pazopanib if randomized to Arm 2. Repeat EKG testing during the screening period is allowed.
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Patients may not have an uncontrolled ventricular arrhythmia or recent (within 3 months) myocardial infarction.
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In addition to the above, 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, patients should be class 2B or better.
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Patients may not have a history of active or unresolved: perforation, abscess or fistula within 28 days prior to registration (either clinically or radiographically).
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Patients must not have myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) or a history of bone marrow biopsy findings at any time consistent with MDS and/or AML.
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For patients with evidence of chronic hepatitis B (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.
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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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HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial.
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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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Patients with central nervous system (CNS)/leptomeningeal disease must have undergone definitive treatment, have no evidence of CNS progression on follow-up imaging performed at least 4 weeks after the CNS-directed therapy is completed, and be off all steroids, in order to be eligible.
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Patients must not have an uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, uncontrolled major seizure disorder, unstable spinal cord compression, superior vena cava syndrome, extensive interstitial bilateral lung disease on high resolution computed tomography (HRCT) scan or any other condition that would limit compliance with study requirements.
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Patients must be able to swallow oral medications.
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Patients may not require concomitant use of known strong CYP3A inhibitors (e.g., itraconazole, telithromycin, clarithromycin, protease inhibitors boosted with ritonavir or cobicistat, indinavir, saquinavir, nelfinavir, boceprevir, telaprevir) or moderate CYP3A inhibitors (e.g., ciprofloxacin, erythromycin, diltiazem, fluconazole, verapamil). The required washout period prior to starting study treatment is 2 weeks.
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Patients may not require concomitant use of known strong (e.g., phenobarbital, enzalutamide, phenytoin, rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine and St John's Wort) or moderate CYP3A inducers (e.g. bosentan, efavirenz, modafinil). The required washout period prior to starting study treatment is 5 weeks for enzalutamide or phenobarbital and 3 weeks for other agents.
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In order to complete the mandatory patient-completed measure, participants must be able to speak and/or read English and Spanish. Non-English or non-Spanish readers may still participate in the study but are not required to complete the PRO-CTCAE side effect surveys.
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For all patients, prior to randomization and as part of eligibility, the investigator must select the agent which the patient would receive if assigned to the investigator's choice arm, prior to randomization. The patient must meet all eligibility criteria for that agent during screening and prior to randomization.
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Patients without central venous access must be willing to undergo placement of central venous access (i.e. port or peripherally inserted central catheter [PICC] line, per institutional practice) if assigned to the investigator's choice arm and if the investigator intends to treat the patient with trabectedin. The site must be able to place central venous access within 10 days of registration/randomization.
Studijní plán
Jak je studie koncipována?
Detaily designu
- Primární účel: Léčba
- Přidělení: Randomizované
- Intervenční model: Paralelní přiřazení
- Maskování: Žádné (otevřený štítek)
Počet zbraní
Zbraně a zásahy
Skupina účastníků / ArmSkupina účastníků / Arm |
Intervence / LéčbaIntervence / Léčba |
|---|---|
|
Experimentální: Arm 1 (olaparib, temozolomide)
Patients receive temozolomide PO QD on days 1-7 of each cycle and olaparib PO BID on days 1-7 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan or MRI and/or bone scans throughout the trial. Patients also undergo collection of blood samples throughout the trial. |
Undergo MRI
Ostatní jména:
Given PO
Ostatní jména:
Undergo MUGA
Ostatní jména:
Undergo collection of blood samples
Ostatní jména:
Undergo CT scan
Ostatní jména:
Given PO
Ostatní jména:
Undergo bone scan
Ostatní jména:
Undergo TTE
Ostatní jména:
|
|
Aktivní komparátor: Arm 2 (trabectedin, pazopanib)
Patients receive trabectedin IV continuously over 24 hours on day 1 of each cycle or pazopanib PO QD on days 1-21 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan or MRI and/or bone scans throughout the trial. Patients also undergo TTE or MUGA on study and as clinically indicated, as well as collection of blood samples throughout the trial. |
Undergo MRI
Ostatní jména:
Undergo MUGA
Ostatní jména:
Undergo collection of blood samples
Ostatní jména:
Undergo CT scan
Ostatní jména:
Undergo bone scan
Ostatní jména:
Undergo TTE
Ostatní jména:
Given PO
Ostatní jména:
Given IV
Ostatní jména:
|
Co je měření studie?
Primární výstupní opatření
Primární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
|
Progression Free Survival (PFS) (Phase II)
Časové okno: Time between the date of randomization and the earliest of disease progression or death, assessed up to 1 year
|
Will be estimated using the Kaplan-Meier method, where the stratified log-rank test will be used to compare the distributions across the treatment arms. PFS rates at 1 year will also be reported, along with 95% confidence intervals. Univariable and multivariable Cox models stratified by the stratification factors used in the randomization will be assessed as well. |
Time between the date of randomization and the earliest of disease progression or death, assessed up to 1 year
|
|
Overall Survival (OS) (Phase III)
Časové okno: Time between the date of randomization and the date of death from any cause, assessed up to 5 years
|
Will be estimated using the Kaplan-Meier method, where the stratified log-rank test will be used to compare the distributions across the treatment arms. OS rates at 1 year, 2 years, and 5 years will also be reported, along with 95% confidence intervals. Univariable and multivariable Cox models stratified by the stratification factors used in the randomization will be assessed as well. |
Time between the date of randomization and the date of death from any cause, assessed up to 5 years
|
Sekundární výstupní opatření
Sekundární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
|
Overall Response Rate
Časové okno: Up to 5 years
|
Will be estimated by dividing the number of evaluable patients that achieve a confirmed response (partial response [PR] or better) by the total number of evaluable patients. This estimate will be calculated by arm and will also include a 95% confidence interval using the properties of the binomial distribution, and compared between the arms using a chi-square test. |
Up to 5 years
|
|
Duration of Response (DOR)
Časové okno: Time from first evidence of response until disease progression (or death), assessed up to 5 years
|
This analysis is restricted to those patients that achieved a confirmed response (PR or better). Patients that go off of study treatment prior to progression will have their DOR time censored at that time. |
Time from first evidence of response until disease progression (or death), assessed up to 5 years
|
|
Disease Control Rate
Časové okno: Up to 6 weeks
|
Will be estimated using the number of patients that achieve complete response, partial response, or stable disease at the 6 week assessment divided by all evaluable patients. This estimate will be calculated by arm and will also include a 95% confidence interval using the properties of the binomial distribution, and compared between the arms using a chi-square test. |
Up to 6 weeks
|
|
Incidence of Adverse Events
Časové okno: Up to 4 weeks after the end of study treatment
|
Adverse events will be recorded using National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 for each patient. Frequency tables and summary statistics will be used and with the appropriate methods of evaluating categorical and continuous data. In addition, patient reported safety and tolerability will be assessed using Patient-Reported Outcomes (PRO)-CTCAE for a prespecified group of expected toxicities. PRO-CTCAE assessments will occur prior to registration and on day 1 of every cycle during treatment. Collection of PRO-CTCAE will be discontinued after cycle 11. |
Up to 4 weeks after the end of study treatment
|
Spolupracovníci a vyšetřovatelé
Sponzor
Sponzor
Vyšetřovatelé
Vyšetřovatelé
- Vrchní vyšetřovatel: Matthew Ingham, Alliance for Clinical Trials in Oncology
Termíny studijních záznamů
Hlavní termíny studia
Začátek studia (Aktuální)
Začátek studia
Primární dokončení (Aktuální)
Primární dokončení
Dokončení studie (Odhadovaný)
Dokončení studie
Termíny zápisu do studia
První předloženo
První předloženo
První předloženo, které splnilo kritéria kontroly kvality
První předloženo, které splnilo kritéria kontroly kvality
První zveřejněno (Aktuální)
První zveřejněno
Aktualizace studijních záznamů
Poslední zveřejněná aktualizace (Aktuální)
Poslední zveřejněná aktualizace
Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality
Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality
Naposledy ověřeno
Naposledy ověřeno
Více informací
Termíny související s touto studií
Další relevantní podmínky MeSH
- Organické chemikálie
- Heterocyklické sloučeniny, 1 kruh
- Heterocyklické sloučeniny
- Heterocyklické sloučeniny, 2-prsten
- Heterocyklické sloučeniny, fúzované kroužek
- Vyšetřovací techniky
- Klinické laboratorní techniky
- Diagnostické techniky a postupy
- Diagnóza
- Azoly
- Dacarbazine
- Triazenes
- Imidazoly
- Techniky chemie, analytické
- Analýza spektra
- Dioxoly
- Tetrahydroisochinoliny
- Isochinoliny
- Temozolomid
- Trabektedin
- Manipulace se vzorkem
- Magnetická rezonanční spektroskopie
- Olaparib
- Pazopanib
Další identifikační čísla studie
Další identifikační čísla studie
- NCI-2022-05065
- U10CA180821 (Grant/smlouva NIH USA)
- NCI-2022-05065 (Identifikátor registru: CTRP (Clinical Trial Reporting Program))
- A092104 (Jiný identifikátor: CTEP)
- A092104 (Jiný identifikátor: Alliance for Clinical Trials in Oncology)
Plán pro data jednotlivých účastníků (IPD)
Plánujete sdílet data jednotlivých účastníků (IPD)?
Popis plánu IPD
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.
Informace o lécích a zařízeních, studijní dokumenty
Studuje lékový produkt regulovaný americkým FDA
Studuje produkt zařízení regulovaný americkým úřadem FDA
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