Testing Olaparib and Temozolomide Versus the Usual Treatment for Uterine Leiomyosarcoma After Chemotherapy Has Stopped Working
A Randomized Phase 2/3 Study of Olaparib Plus Temozolomide Versus Investigator's Choice for the Treatment of Patients With Advanced Uterine Leiomyosarcoma After Progression on Prior Chemotherapy
3 other identifiers
interventional
74
2 countries
145
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_2
Started Mar 2023
Typical duration for phase_2
145 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
June 22, 2022
CompletedFirst Posted
Study publicly available on registry
June 27, 2022
CompletedStudy Start
First participant enrolled
March 30, 2023
CompletedPrimary Completion
Last participant's last visit for primary outcome
August 13, 2024
CompletedResults Posted
Study results publicly available
April 8, 2026
CompletedStudy Completion
Last participant's last visit for all outcomes
January 30, 2027
ExpectedApril 8, 2026
February 1, 2026
1.4 years
June 22, 2022
February 25, 2026
March 20, 2026
Conditions
Outcome Measures
Primary Outcomes (2)
Progression Free Survival (PFS) (Phase II)
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)
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
Secondary Outcomes (4)
Overall Response Rate
Up to 5 years
Duration of Response (DOR)
Time from first evidence of response until disease progression (or death), assessed up to 5 years
Disease Control Rate
Up to 6 weeks
Incidence of Adverse Events
Up to 4 weeks after the end of study treatment
Study Arms (2)
Arm 1 (olaparib, temozolomide)
EXPERIMENTALPatients 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.
Arm 2 (trabectedin, pazopanib)
ACTIVE COMPARATORPatients 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.
Interventions
Undergo collection of blood samples
Undergo bone scan
Undergo CT scan
Undergo MRI
Given PO
Given IV
Undergo TTE
Undergo MUGA
Given PO
Eligibility Criteria
You may qualify if:
- 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.
- Metastatic or locally advanced and surgically unresectable disease, in the opinion of the treating investigator.
- 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.
- 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
- Age \>= 18 years.
- Eastern Cooperative Oncology Group (ECOG) Performance Status =\< 2.
- 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.
- Patients may not have received prior treatment with any PARP inhibitor, temozolomide or dacarbazine (IV analogue of temozolomide).
- 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.
- 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.
- Patients must have completed all prior anti-cancer treatment, including radiation, \>= 28 days prior to registration.
- 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.
- Absolute neutrophil count (ANC) \>= 1500/mm\^3 (within =\< 28 days prior to registration).
- Platelet count \>= 100,000/mm\^3 (within =\< 28 days prior to registration).
- Creatinine =\< 1.5 \* upper limit of normal (ULN) (within =\< 28 days prior to registration).
- +24 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (145)
University of Alabama at Birmingham Cancer Center
Birmingham, Alabama, 35233, United States
Alaska Women's Cancer Care
Anchorage, Alaska, 99508, United States
Mayo Clinic Hospital in Arizona
Phoenix, Arizona, 85054, United States
City of Hope Comprehensive Cancer Center
Duarte, California, 91010, United States
Epic Care-Dublin
Dublin, California, 94568, United States
Epic Care Partners in Cancer Care
Emeryville, California, 94608, United States
City of Hope at Irvine Lennar
Irvine, California, 92618, United States
Contra Costa Regional Medical Center
Martinez, California, 94553-3156, United States
Epic Care Cyberknife Center
Walnut Creek, California, 94597, United States
UCHealth University of Colorado Hospital
Aurora, Colorado, 80045, United States
UCHealth Memorial Hospital Central
Colorado Springs, Colorado, 80909, United States
Memorial Hospital North
Colorado Springs, Colorado, 80920, United States
Poudre Valley Hospital
Fort Collins, Colorado, 80524, United States
Cancer Care and Hematology-Fort Collins
Fort Collins, Colorado, 80528, United States
UCHealth Greeley Hospital
Greeley, Colorado, 80631, United States
Medical Center of the Rockies
Loveland, Colorado, 80538, United States
Smilow Cancer Hospital-Derby Care Center
Derby, Connecticut, 06418, United States
Smilow Cancer Hospital Care Center-Fairfield
Fairfield, Connecticut, 06824, United States
Smilow Cancer Hospital Care Center at Glastonbury
Glastonbury, Connecticut, 06033, United States
Smilow Cancer Hospital Care Center at Greenwich
Greenwich, Connecticut, 06830, United States
Smilow Cancer Hospital Care Center - Guilford
Guilford, Connecticut, 06437, United States
Smilow Cancer Hospital Care Center at Saint Francis
Hartford, Connecticut, 06105, United States
Yale University
New Haven, Connecticut, 06520, United States
Yale-New Haven Hospital North Haven Medical Center
North Haven, Connecticut, 06473, United States
Smilow Cancer Hospital Care Center at Long Ridge
Stamford, Connecticut, 06902, United States
Smilow Cancer Hospital-Torrington Care Center
Torrington, Connecticut, 06790, United States
Smilow Cancer Hospital Care Center-Trumbull
Trumbull, Connecticut, 06611, United States
Smilow Cancer Hospital-Waterbury Care Center
Waterbury, Connecticut, 06708, United States
Smilow Cancer Hospital Care Center - Waterford
Waterford, Connecticut, 06385, United States
MedStar Washington Hospital Center
Washington D.C., District of Columbia, 20010, United States
UM Sylvester Comprehensive Cancer Center at Deerfield Beach
Deerfield Beach, Florida, 33442, United States
Mayo Clinic in Florida
Jacksonville, Florida, 32224-9980, United States
University of Miami Miller School of Medicine-Sylvester Cancer Center
Miami, Florida, 33136, United States
UM Sylvester Comprehensive Cancer Center at Plantation
Plantation, Florida, 33324, United States
Lewis Cancer and Research Pavilion at Saint Joseph's/Candler
Savannah, Georgia, 31405, United States
Saint Luke's Cancer Institute - Boise
Boise, Idaho, 83712, United States
Saint Luke's Cancer Institute - Fruitland
Fruitland, Idaho, 83619, United States
Saint Luke's Cancer Institute - Meridian
Meridian, Idaho, 83642, United States
Saint Luke's Cancer Institute - Nampa
Nampa, Idaho, 83687, United States
Saint Luke's Cancer Institute - Twin Falls
Twin Falls, Idaho, 83301, United States
Northwestern University
Chicago, Illinois, 60611, United States
University of Illinois
Chicago, Illinois, 60612, United States
Carle at The Riverfront
Danville, Illinois, 61832, United States
Northwestern Medicine Cancer Center Kishwaukee
DeKalb, Illinois, 60115, United States
Carle Physician Group-Effingham
Effingham, Illinois, 62401, United States
NorthShore University HealthSystem-Evanston Hospital
Evanston, Illinois, 60201, United States
Northwestern Medicine Cancer Center Delnor
Geneva, Illinois, 60134, United States
NorthShore University HealthSystem-Glenbrook Hospital
Glenview, Illinois, 60026, United States
NorthShore University HealthSystem-Highland Park Hospital
Highland Park, Illinois, 60035, United States
Northwestern Medicine Lake Forest Hospital
Lake Forest, Illinois, 60045, United States
Carle Physician Group-Mattoon/Charleston
Mattoon, Illinois, 61938, United States
Carle Cancer Center
Urbana, Illinois, 61801, United States
Northwestern Medicine Cancer Center Warrenville
Warrenville, Illinois, 60555, United States
Mary Greeley Medical Center
Ames, Iowa, 50010, United States
McFarland Clinic - Ames
Ames, Iowa, 50010, United States
McFarland Clinic - Boone
Boone, Iowa, 50036, United States
Heartland Oncology and Hematology LLP
Council Bluffs, Iowa, 51503, United States
Mercy Medical Center - Des Moines
Des Moines, Iowa, 50314, United States
McFarland Clinic - Trinity Cancer Center
Fort Dodge, Iowa, 50501, United States
University of Iowa/Holden Comprehensive Cancer Center
Iowa City, Iowa, 52242, United States
McFarland Clinic - Jefferson
Jefferson, Iowa, 50129, United States
McFarland Clinic - Marshalltown
Marshalltown, Iowa, 50158, United States
Baptist Health Lexington
Lexington, Kentucky, 40503, United States
Our Lady of the Lake Medical Oncology
Baton Rouge, Louisiana, 70817, United States
University Medical Center New Orleans
New Orleans, Louisiana, 70112, United States
MaineHealth Maine Medical Center- Scarborough
Scarborough, Maine, 04074, United States
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215, United States
University of Michigan Rogel Cancer Center
Ann Arbor, Michigan, 48109, United States
Bronson Battle Creek
Battle Creek, Michigan, 49017, United States
Corewell Health Grand Rapids Hospitals - Butterworth Hospital
Grand Rapids, Michigan, 49503, United States
Trinity Health Grand Rapids Hospital
Grand Rapids, Michigan, 49503, United States
Bronson Methodist Hospital
Kalamazoo, Michigan, 49007, United States
West Michigan Cancer Center
Kalamazoo, Michigan, 49007, United States
Beacon Kalamazoo Cancer Center
Kalamazoo, Michigan, 49009, United States
Trinity Health Muskegon Hospital
Muskegon, Michigan, 49444, United States
Cancer and Hematology Centers of Western Michigan - Norton Shores
Norton Shores, Michigan, 49444, United States
Corewell Health Reed City Hospital
Reed City, Michigan, 49677, United States
Corewell Health Lakeland Hospitals - Marie Yeager Cancer Center
Saint Joseph, Michigan, 49085, United States
Munson Medical Center
Traverse City, Michigan, 49684, United States
University of Michigan Health - West
Wyoming, Michigan, 49519, United States
Mercy Hospital
Coon Rapids, Minnesota, 55433, United States
Fairview Southdale Hospital
Edina, Minnesota, 55435, United States
Abbott-Northwestern Hospital
Minneapolis, Minnesota, 55407, United States
Mayo Clinic in Rochester
Rochester, Minnesota, 55905, United States
Park Nicollet Clinic - Saint Louis Park
Saint Louis Park, Minnesota, 55416, United States
Regions Hospital
Saint Paul, Minnesota, 55101, United States
United Hospital
Saint Paul, Minnesota, 55102, United States
Siteman Cancer Center at West County Hospital
Creve Coeur, Missouri, 63141, United States
Washington University School of Medicine
St Louis, Missouri, 63110, United States
Siteman Cancer Center-South County
St Louis, Missouri, 63129, United States
Mercy Hospital Saint Louis
St Louis, Missouri, 63141, United States
Nebraska Cancer Specialists/Oncology Hematology West PC - MECC
Omaha, Nebraska, 68114, United States
Nebraska Methodist Hospital
Omaha, Nebraska, 68114, United States
Oncology Associates PC
Omaha, Nebraska, 68114, United States
Memorial Sloan Kettering Basking Ridge
Basking Ridge, New Jersey, 07920, United States
Memorial Sloan Kettering Monmouth
Middletown, New Jersey, 07748, United States
Memorial Sloan Kettering Bergen
Montvale, New Jersey, 07645, United States
Roswell Park Cancer Institute
Buffalo, New York, 14263, United States
Memorial Sloan Kettering Commack
Commack, New York, 11725, United States
Memorial Sloan Kettering Westchester
Harrison, New York, 10604, United States
Northwell Health/Center for Advanced Medicine
Lake Success, New York, 11042, United States
Memorial Sloan Kettering Cancer Center
New York, New York, 10065, United States
Memorial Sloan Kettering Nassau
Uniondale, New York, 11553, United States
UNC Lineberger Comprehensive Cancer Center
Chapel Hill, North Carolina, 27599, United States
Duke University Medical Center
Durham, North Carolina, 27710, United States
ECU Health Medical Center
Greenville, North Carolina, 27834, United States
UH Seidman Cancer Center at UH Avon Health Center
Avon, Ohio, 44011, United States
UHHS-Chagrin Highlands Medical Center
Beachwood, Ohio, 44122, United States
Case Western Reserve University
Cleveland, Ohio, 44106, United States
Cleveland Clinic Cancer Center/Fairview Hospital
Cleveland, Ohio, 44111, United States
Cleveland Clinic Foundation
Cleveland, Ohio, 44195, United States
Hillcrest Hospital Cancer Center
Mayfield Heights, Ohio, 44124, United States
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, 73104, United States
Clackamas Radiation Oncology Center
Clackamas, Oregon, 97015, United States
Legacy Mount Hood Medical Center
Gresham, Oregon, 97030, United States
Providence Newberg Medical Center
Newberg, Oregon, 97132, United States
Providence Willamette Falls Medical Center
Oregon City, Oregon, 97045, United States
Legacy Good Samaritan Hospital and Medical Center
Portland, Oregon, 97210, United States
Providence Portland Medical Center
Portland, Oregon, 97213, United States
Providence Saint Vincent Medical Center
Portland, Oregon, 97225, United States
Oregon Health and Science University
Portland, Oregon, 97239, United States
Legacy Meridian Park Hospital
Tualatin, Oregon, 97062, United States
Thomas Jefferson University Hospital
Philadelphia, Pennsylvania, 19107, United States
Fox Chase Cancer Center
Philadelphia, Pennsylvania, 19111, United States
Asplundh Cancer Pavilion
Willow Grove, Pennsylvania, 19090, United States
Women and Infants Hospital
Providence, Rhode Island, 02905, United States
Smilow Cancer Hospital Care Center - Westerly
Westerly, Rhode Island, 02891, United States
Saint Joseph's/Candler - Bluffton Campus
Bluffton, South Carolina, 29910, United States
Medical University of South Carolina
Charleston, South Carolina, 29425, United States
Vanderbilt University/Ingram Cancer Center
Nashville, Tennessee, 37232, United States
VCU Massey Cancer Center at Stony Point
Richmond, Virginia, 23235, United States
VCU Massey Comprehensive Cancer Center
Richmond, Virginia, 23298, United States
Fred Hutchinson Cancer Center
Seattle, Washington, 98109, United States
University of Washington Medical Center - Montlake
Seattle, Washington, 98195, United States
Legacy Cancer Institute Medical Oncology and Day Treatment
Vancouver, Washington, 98684, United States
Legacy Salmon Creek Hospital
Vancouver, Washington, 98686, United States
West Virginia University Charleston Division
Charleston, West Virginia, 25304, United States
Marshfield Medical Center-EC Cancer Center
Eau Claire, Wisconsin, 54701, United States
Marshfield Medical Center-Marshfield
Marshfield, Wisconsin, 54449, United States
Medical College of Wisconsin
Milwaukee, Wisconsin, 53226, United States
Marshfield Medical Center - Minocqua
Minocqua, Wisconsin, 54548, United States
Marshfield Medical Center-Rice Lake
Rice Lake, Wisconsin, 54868, United States
Marshfield Medical Center-River Region at Stevens Point
Stevens Point, Wisconsin, 54482, United States
Marshfield Medical Center - Weston
Weston, Wisconsin, 54476, United States
Centro Comprensivo de Cancer de UPR
San Juan, 00927, Puerto Rico
MeSH Terms
Interventions
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Dr. Matthew Ingham
- Organization
- Perlmutter Cancer Center NYU Langone Health
Study Officials
- PRINCIPAL INVESTIGATOR
Matthew Ingham
Alliance for Clinical Trials in Oncology
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- LTE60
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
June 22, 2022
First Posted
June 27, 2022
Study Start
March 30, 2023
Primary Completion
August 13, 2024
Study Completion (Estimated)
January 30, 2027
Last Updated
April 8, 2026
Results First Posted
April 8, 2026
Record last verified: 2026-02
Data Sharing
- IPD Sharing
- Will share
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.