Testing Olaparib and Temozolomide Versus the Usual Treatment for Uterine Leiomyosarcoma After Chemotherapy Has Stopped Working
NCT ID: NCT05432791
Last Updated: 2025-12-31
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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ACTIVE_NOT_RECRUITING
PHASE2/PHASE3
190 participants
INTERVENTIONAL
2023-03-30
2030-03-09
Brief Summary
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Detailed Description
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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)
EXPLORATORY OBJECTIVE:
I. To collect results of tumor genomic testing previously conducted as part of clinical care (when available) and (a) to determine the proportion of patients with a genomic alteration in a homologous recombination (HR) pathway gene and (b) to evaluate for any relationship between the presence of such an alteration and clinical benefit from olaparib and temozolomide. (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.
Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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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.
Biospecimen Collection
Undergo collection of blood samples
Bone Scan
Undergo bone scan
Computed Tomography
Undergo CT scan
Magnetic Resonance Imaging
Undergo MRI
Multigated Acquisition Scan
Undergo MUGA
Olaparib
Given PO
Temozolomide
Given PO
Transthoracic Echocardiography Test
Undergo TTE
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.
Biospecimen Collection
Undergo collection of blood samples
Bone Scan
Undergo bone scan
Computed Tomography
Undergo CT scan
Magnetic Resonance Imaging
Undergo MRI
Multigated Acquisition Scan
Undergo MUGA
Pazopanib
Given PO
Trabectedin
Given IV
Transthoracic Echocardiography Test
Undergo TTE
Interventions
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Biospecimen Collection
Undergo collection of blood samples
Bone Scan
Undergo bone scan
Computed Tomography
Undergo CT scan
Magnetic Resonance Imaging
Undergo MRI
Multigated Acquisition Scan
Undergo MUGA
Olaparib
Given PO
Pazopanib
Given PO
Temozolomide
Given PO
Trabectedin
Given IV
Transthoracic Echocardiography Test
Undergo TTE
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* 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).
* If creatinine \> 1.5 \* ULN, then creatinine clearance (CrCl) must be \> 50 mL/min, per Cockcroft-Gault method.
* Hemoglobin \>= 9 g/dL (within =\< 28 days prior to registration).
* No transfusions =\< 14 days before cycle 1 day 1 (C1D1).
* Total bilirubin =\< 1.5 x ULN (within =\< 28 days prior to registration).
* If documented Gilbert's: =\< 2.0 x ULN.
* Aspartate aminotransferase/alanine aminotransferase (AST/ALT) =\< 3 x ULN (within =\< 28 days prior to registration).
* 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.
* 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.
* Patients may not have an uncontrolled ventricular arrhythmia or recent (within 3 months) myocardial infarction.
* 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.
* Patients may not have a history of active or unresolved: perforation, abscess or fistula within 28 days prior to registration (either clinically or radiographically).
* 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.
* For patients with evidence of chronic hepatitis B (HBV) infection, the HBV viral load must be undetectable 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.
* HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial.
* 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.
* 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.
* 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.
* Patients must be able to swallow oral medications.
* 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.
* 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.
* 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.
* 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.
* 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.
18 Years
ALL
No
Sponsors
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National Cancer Institute (NCI)
NIH
Responsible Party
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Principal Investigators
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Brian Van Tine
Role: PRINCIPAL_INVESTIGATOR
Alliance for Clinical Trials in Oncology
Locations
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University of Alabama at Birmingham Cancer Center
Birmingham, Alabama, United States
Alaska Women's Cancer Care
Anchorage, Alaska, United States
Mayo Clinic Hospital in Arizona
Phoenix, Arizona, United States
City of Hope Comprehensive Cancer Center
Duarte, California, United States
Epic Care-Dublin
Dublin, California, United States
Epic Care Partners in Cancer Care
Emeryville, California, United States
City of Hope at Irvine Lennar
Irvine, California, United States
Contra Costa Regional Medical Center
Martinez, California, United States
Epic Care Cyberknife Center
Walnut Creek, California, United States
UCHealth University of Colorado Hospital
Aurora, Colorado, United States
UCHealth Memorial Hospital Central
Colorado Springs, Colorado, United States
Memorial Hospital North
Colorado Springs, Colorado, United States
Poudre Valley Hospital
Fort Collins, Colorado, United States
Cancer Care and Hematology-Fort Collins
Fort Collins, Colorado, United States
UCHealth Greeley Hospital
Greeley, Colorado, United States
Medical Center of the Rockies
Loveland, Colorado, United States
Smilow Cancer Hospital-Derby Care Center
Derby, Connecticut, United States
Smilow Cancer Hospital Care Center-Fairfield
Fairfield, Connecticut, United States
Smilow Cancer Hospital Care Center at Glastonbury
Glastonbury, Connecticut, United States
Smilow Cancer Hospital Care Center at Greenwich
Greenwich, Connecticut, United States
Smilow Cancer Hospital Care Center - Guilford
Guilford, Connecticut, United States
Smilow Cancer Hospital Care Center at Saint Francis
Hartford, Connecticut, United States
Yale University
New Haven, Connecticut, United States
Yale-New Haven Hospital North Haven Medical Center
North Haven, Connecticut, United States
Smilow Cancer Hospital Care Center at Long Ridge
Stamford, Connecticut, United States
Smilow Cancer Hospital-Torrington Care Center
Torrington, Connecticut, United States
Smilow Cancer Hospital Care Center-Trumbull
Trumbull, Connecticut, United States
Smilow Cancer Hospital-Waterbury Care Center
Waterbury, Connecticut, United States
Smilow Cancer Hospital Care Center - Waterford
Waterford, Connecticut, United States
MedStar Washington Hospital Center
Washington D.C., District of Columbia, United States
UM Sylvester Comprehensive Cancer Center at Deerfield Beach
Deerfield Beach, Florida, United States
Mayo Clinic in Florida
Jacksonville, Florida, United States
University of Miami Miller School of Medicine-Sylvester Cancer Center
Miami, Florida, United States
UM Sylvester Comprehensive Cancer Center at Plantation
Plantation, Florida, United States
Lewis Cancer and Research Pavilion at Saint Joseph's/Candler
Savannah, Georgia, United States
Saint Luke's Cancer Institute - Boise
Boise, Idaho, United States
Saint Luke's Cancer Institute - Fruitland
Fruitland, Idaho, United States
Saint Luke's Cancer Institute - Meridian
Meridian, Idaho, United States
Saint Luke's Cancer Institute - Nampa
Nampa, Idaho, United States
Saint Luke's Cancer Institute - Twin Falls
Twin Falls, Idaho, United States
Northwestern University
Chicago, Illinois, United States
University of Illinois
Chicago, Illinois, United States
Carle at The Riverfront
Danville, Illinois, United States
Northwestern Medicine Cancer Center Kishwaukee
DeKalb, Illinois, United States
Carle Physician Group-Effingham
Effingham, Illinois, United States
NorthShore University HealthSystem-Evanston Hospital
Evanston, Illinois, United States
Northwestern Medicine Cancer Center Delnor
Geneva, Illinois, United States
NorthShore University HealthSystem-Glenbrook Hospital
Glenview, Illinois, United States
NorthShore University HealthSystem-Highland Park Hospital
Highland Park, Illinois, United States
Northwestern Medicine Lake Forest Hospital
Lake Forest, Illinois, United States
Carle Physician Group-Mattoon/Charleston
Mattoon, Illinois, United States
Carle Cancer Center
Urbana, Illinois, United States
Northwestern Medicine Cancer Center Warrenville
Warrenville, Illinois, United States
Mary Greeley Medical Center
Ames, Iowa, United States
McFarland Clinic - Ames
Ames, Iowa, United States
McFarland Clinic - Boone
Boone, Iowa, United States
Heartland Oncology and Hematology LLP
Council Bluffs, Iowa, United States
Mercy Medical Center - Des Moines
Des Moines, Iowa, United States
McFarland Clinic - Trinity Cancer Center
Fort Dodge, Iowa, United States
University of Iowa/Holden Comprehensive Cancer Center
Iowa City, Iowa, United States
McFarland Clinic - Jefferson
Jefferson, Iowa, United States
McFarland Clinic - Marshalltown
Marshalltown, Iowa, United States
Baptist Health Lexington
Lexington, Kentucky, United States
Our Lady of the Lake Medical Oncology
Baton Rouge, Louisiana, United States
University Medical Center New Orleans
New Orleans, Louisiana, United States
MaineHealth Maine Medical Center- Scarborough
Scarborough, Maine, United States
Dana-Farber Cancer Institute
Boston, Massachusetts, United States
University of Michigan Rogel Cancer Center
Ann Arbor, Michigan, United States
Bronson Battle Creek
Battle Creek, Michigan, United States
Corewell Health Grand Rapids Hospitals - Butterworth Hospital
Grand Rapids, Michigan, United States
Trinity Health Grand Rapids Hospital
Grand Rapids, Michigan, United States
Bronson Methodist Hospital
Kalamazoo, Michigan, United States
West Michigan Cancer Center
Kalamazoo, Michigan, United States
Beacon Kalamazoo Cancer Center
Kalamazoo, Michigan, United States
Trinity Health Muskegon Hospital
Muskegon, Michigan, United States
Cancer and Hematology Centers of Western Michigan - Norton Shores
Norton Shores, Michigan, United States
Corewell Health Reed City Hospital
Reed City, Michigan, United States
Corewell Health Lakeland Hospitals - Marie Yeager Cancer Center
Saint Joseph, Michigan, United States
Munson Medical Center
Traverse City, Michigan, United States
University of Michigan Health - West
Wyoming, Michigan, United States
Mercy Hospital
Coon Rapids, Minnesota, United States
Fairview Southdale Hospital
Edina, Minnesota, United States
Abbott-Northwestern Hospital
Minneapolis, Minnesota, United States
Mayo Clinic in Rochester
Rochester, Minnesota, United States
Park Nicollet Clinic - Saint Louis Park
Saint Louis Park, Minnesota, United States
Regions Hospital
Saint Paul, Minnesota, United States
United Hospital
Saint Paul, Minnesota, United States
Siteman Cancer Center at West County Hospital
Creve Coeur, Missouri, United States
Washington University School of Medicine
St Louis, Missouri, United States
Siteman Cancer Center-South County
St Louis, Missouri, United States
Mercy Hospital Saint Louis
St Louis, Missouri, United States
Nebraska Cancer Specialists/Oncology Hematology West PC - MECC
Omaha, Nebraska, United States
Nebraska Methodist Hospital
Omaha, Nebraska, United States
Oncology Associates PC
Omaha, Nebraska, United States
Memorial Sloan Kettering Basking Ridge
Basking Ridge, New Jersey, United States
Memorial Sloan Kettering Monmouth
Middletown, New Jersey, United States
Memorial Sloan Kettering Bergen
Montvale, New Jersey, United States
Roswell Park Cancer Institute
Buffalo, New York, United States
Memorial Sloan Kettering Commack
Commack, New York, United States
Memorial Sloan Kettering Westchester
Harrison, New York, United States
Northwell Health/Center for Advanced Medicine
Lake Success, New York, United States
Memorial Sloan Kettering Cancer Center
New York, New York, United States
Memorial Sloan Kettering Nassau
Uniondale, New York, United States
UNC Lineberger Comprehensive Cancer Center
Chapel Hill, North Carolina, United States
Duke University Medical Center
Durham, North Carolina, United States
ECU Health Medical Center
Greenville, North Carolina, United States
UH Seidman Cancer Center at UH Avon Health Center
Avon, Ohio, United States
UHHS-Chagrin Highlands Medical Center
Beachwood, Ohio, United States
Case Western Reserve University
Cleveland, Ohio, United States
Cleveland Clinic Cancer Center/Fairview Hospital
Cleveland, Ohio, United States
Cleveland Clinic Foundation
Cleveland, Ohio, United States
Hillcrest Hospital Cancer Center
Mayfield Heights, Ohio, United States
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, United States
Clackamas Radiation Oncology Center
Clackamas, Oregon, United States
Legacy Mount Hood Medical Center
Gresham, Oregon, United States
Providence Newberg Medical Center
Newberg, Oregon, United States
Providence Willamette Falls Medical Center
Oregon City, Oregon, United States
Legacy Good Samaritan Hospital and Medical Center
Portland, Oregon, United States
Providence Portland Medical Center
Portland, Oregon, United States
Providence Saint Vincent Medical Center
Portland, Oregon, United States
Oregon Health and Science University
Portland, Oregon, United States
Legacy Meridian Park Hospital
Tualatin, Oregon, United States
Thomas Jefferson University Hospital
Philadelphia, Pennsylvania, United States
Fox Chase Cancer Center
Philadelphia, Pennsylvania, United States
Asplundh Cancer Pavilion
Willow Grove, Pennsylvania, United States
Women and Infants Hospital
Providence, Rhode Island, United States
Smilow Cancer Hospital Care Center - Westerly
Westerly, Rhode Island, United States
Saint Joseph's/Candler - Bluffton Campus
Bluffton, South Carolina, United States
Medical University of South Carolina
Charleston, South Carolina, United States
Vanderbilt University/Ingram Cancer Center
Nashville, Tennessee, United States
VCU Massey Cancer Center at Stony Point
Richmond, Virginia, United States
VCU Massey Comprehensive Cancer Center
Richmond, Virginia, United States
Fred Hutchinson Cancer Center
Seattle, Washington, United States
University of Washington Medical Center - Montlake
Seattle, Washington, United States
Legacy Cancer Institute Medical Oncology and Day Treatment
Vancouver, Washington, United States
Legacy Salmon Creek Hospital
Vancouver, Washington, United States
West Virginia University Charleston Division
Charleston, West Virginia, United States
Marshfield Medical Center-EC Cancer Center
Eau Claire, Wisconsin, United States
Marshfield Medical Center-Marshfield
Marshfield, Wisconsin, United States
Medical College of Wisconsin
Milwaukee, Wisconsin, United States
Marshfield Medical Center - Minocqua
Minocqua, Wisconsin, United States
Marshfield Medical Center-Rice Lake
Rice Lake, Wisconsin, United States
Marshfield Medical Center-River Region at Stevens Point
Stevens Point, Wisconsin, United States
Marshfield Medical Center - Weston
Weston, Wisconsin, United States
Centro Comprensivo de Cancer de UPR
San Juan, , Puerto Rico
Countries
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Provided Documents
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Document Type: Informed Consent Form
Other Identifiers
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NCI-2022-05065
Identifier Type: REGISTRY
Identifier Source: secondary_id
A092104
Identifier Type: OTHER
Identifier Source: secondary_id
A092104
Identifier Type: OTHER
Identifier Source: secondary_id
NCI-2022-05065
Identifier Type: -
Identifier Source: org_study_id
NCT05633381
Identifier Type: -
Identifier Source: nct_alias