NCT04181060ClinicalTrials.gov

Osimertinib With or Without Bevacizumab as Initial Treatment for Patients With EGFR-Mutant Lung Cancer

Randomized Phase III Study of Combination Osimertinib (AZD9291) and Bevacizumab Versus Osimertinib (AZD9291) Alone as First-Line Treatment for Patients With Metastatic EGFR-Mutant Non-Small Cell Lung Cancer (NSCLC)

En reclutamientoAdmite participantes ahora, según el registro.

Contactar con este estudio

En resumen

Fase 3300 participantes buscados603 centros1 país

Categorías

Oncología75%Respiratorio25%

Registrado en 1 registro

ClinicalTrials.govNCT04181060Abrir este registro en ClinicalTrials.govSincronizado hace 2 semanas

Un mismo estudio puede estar registrado en varios registros. Lo mostramos una sola vez y enlazamos con todos los registros que tenemos.

La información del ensayo se muestra tal como la publicó el registro, en su idioma original.

¿Le interesa este estudio?

Iniciar sesión o cree una cuenta para registrar su interés y seguir este estudio.

How this study is set up

The points below are drawn from the public registry record for this study. Each one cites the field or sentence it came from. A dash (—) means the record does not state something — not that it is missing or wrong. Many well-run studies, especially small ones, leave some of these blank.

Present: Registered before enrolment beganFirst posted 2019-11-29; recorded start 2020-12-28
Present: Has a defined primary outcomeA primary outcome measure is listed in the record
Present: The primary outcome states a time frameThe primary outcome measure records a time frame
Present: Participants are randomly assignedAllocation is recorded as randomised
Present: Has a comparison groupThe record lists a placebo or comparator arm, or more than one study arm
Not stated: Open label (no blinding)Masking is recorded as none (open label)
Not stated: An ethics committee is not stated in the registry recordThis registry's ingested record has no ethics-committee field
Not stated: Regulatory oversight (such as an IND or IDE) is not stated in the registry recordThis registry's ingested record has no regulatory-authorisation field
Not stated: A data monitoring committee is not stated in the registry recordThis registry's ingested record has no data-monitoring-committee fieldA data monitoring committee is not required for many smaller studies, and its absence here is not unusual.
Present: No cost to participants is mentioned in the recordChecked the summary, description and eligibility text; no cost-to-participant phrase found
Present: Sponsor has 1548 other studies in this databaseCounted from the lead sponsor named in the record (National Cancer Institute (NCI))
Present: Sponsor has posted results for at least one studyBased on the sponsor’s studies in this database

The record lists 5 conditions.
Lead sponsor type recorded as: US National Institutes of Health.
Intervention regulatory context: investigational, within a phased regulatory pathway.

These are facts from the public registry record, not a judgement about the study. Discuss any trial with your own doctor before taking part.

What these facts mean, and what to ask · ruleset v1

Trial stature

Three independent measures of this study, described from its registry record — not a recommendation about it. A rigorous study by investigators nobody has heard of is better evidence than a weak study led by a famous one. How these are scored.

Methodological rigourSTRONG

A strong methodological design for a phase 3 study, judged from its ClinicalTrials.gov record.

How this score is built

Randomised allocation20/20
Participants are randomly allocated between arms
Blinding0/20
Open-label
Control arm15/15
Active-comparator control arm
Primary-outcome specificity10/10
Named primary outcome with a defined time frame
Endpoint type10/10
Mortality / MACE endpoint (hard clinical outcome)
Multi-centre8/8
Multi-centre: 604 sites
Data monitoring committee0/7
No data monitoring committee stated
Prospective registration5/5
Registered before the study start date
Protocol / SAP posted0/5
No protocol or SAP posted to the registry

ScaleMEDIUM

A medium-sized study: 300 participants (target), run at 603 sites.

How this score is built

Enrolment24/40
300 participants (target)
Site count25/25
604 sites
Country count0/15
Single country
Planned duration10/10
Planned over about 73 months
Sponsor scale10/10
National Cancer Institute (NCI) has led 1,534 trials in our corpus

Investigator standingUNKNOWN

We have no verifiable track record for the investigator named on this trial. That is common for early-career investigators and for records held outside ClinicalTrials.gov — it is not a negative signal.

How this score is built

Investigator standing0/100
No investigator recorded in the registry for this trial

These describe the registry record only, and today we hold ClinicalTrials.gov data. Absent fields lower a score, and absence often reflects registration practice rather than study quality. A high-stature trial is not necessarily safer or a better choice for you — enrolling in a large definitive trial can mean a higher chance of receiving placebo, while a small early-phase study may be the only route to a new therapy.

Resumen

This phase III trial compares the effect of bevacizumab and osimertinib combination vs. osimertinib alone for the treatment of non-small cell lung cancer that has spread outside of the lungs (stage IIIB-IV) and has a change (mutation) in a gene called EGFR. The EGFR protein is involved in cell signaling pathways that control cell division and survival. Sometimes, mutations in the EGFR gene cause EGFR proteins to be made in higher than normal amounts on some types of cancer cells. This causes cancer cells to divide more rapidly. Osimertinib may stop the growth of tumor cells by blocking EGFR that is needed for cell growth in this type of cancer. Bevacizumab is in a class of medications called antiangiogenic agents. It works by stopping the formation of blood vessels that bring oxygen and nutrients to tumor. This may slow the growth and spread of tumor. Giving osimertinib with bevacizumab may control cancer for longer and help patients live longer as compared to osimertinib alone.

PRIMARY OBJECTIVE: I. To evaluate progression-free survival (PFS) of osimertinib (AZD9291) and bevacizumab versus osimertinib (AZD9291) alone as first-line treatment for patients with metastatic EGFR-mutant lung cancers. SECONDARY OBJECTIVES: I. To evaluate overall survival (OS). II. To evaluate best objective response rate and duration of objective response. III. To evaluate time to central nervous system (CNS) progression and CNS PFS. IV. To evaluate toxicity of the combination regimen. CORRELATIVE OBJECTIVES: I. To characterize mechanisms of resistance to osimertinib (AZD9291) and osimertinib (AZD9291) with bevacizumab first-line therapy through post-progression circulating tumor-derived deoxyribonucleic acid (ctDNA). II. To assess for ctDNA clearance on study treatment and associate ctDNA clearance with clinical outcomes. OUTLINE: Patients are randomized to 1 of 2 arms. ARM A: Patients receive osimertinib orally (PO) once daily (QD) on days 1-21. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. ARM B: Patients receive osimertinib PO QD on days 1-21 and bevacizumab intravenously (IV) over 30-90 minutes on day 1. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients undergo echocardiography (ECHO), multigated acquisition scan (MUGA), computed tomography (CT) and may undergo magnetic resonance imaging (MRI) and blood and urine sample collection on study. After completion of study treatment, patients are followed up every 3 months for 10 years.

Afecciones

Advanced Lung Non-Squamous Non-Small Cell Carcinoma
Metastatic Lung Non-Squamous Non-Small Cell Carcinoma
Recurrent Lung Non-Squamous Non-Small Cell Carcinoma
Stage IIIB Lung Cancer AJCC v8
Stage IV Lung Cancer AJCC v8

Elegibilidad

Elegibilidad
Sexo	Todos
Edades	18 Years – Sin máximo
Voluntarios sanos	No

Elegibilidad tal como figura en el registro

Inclusion Criteria: * Patient must have a pathologically-confirmed diagnosis of non-squamous, non-small cell lung cancer (NSCLC) * Patient must have advanced disease, defined as - either stage IV disease, stage IIIB disease not amenable to definitive multi-modality therapy, or recurrent disease after a prior diagnosis of stage I-III disease. All staging is via the American Joint Committee on Cancer (AJCC)/International Association for the Study of Lung Cancer (IASLC) 8th edition staging criteria * Patient must have somatic activating sensitizing mutation in EGFR (e.g. but not limited to Exon 19 deletion, L858R, E709X, G719X, exon 19 insertions, L861Q, S768I). Patients with non-sensitizing mutations in EGFR (EGFR exon 20 insertions) are not eligible. Test results originating from a Clinical Laboratory Improvement Act (CLIA)-certified or similarly accredited laboratory are acceptable; no specific assay is mandated. Plasma, cytology, or tumor tissue can be utilized for mutation testing * Patient must not have received any prior treatment with an anti-VEGF agent * NOTE: Prior treatment with an EGFR TKI is not allowed, however if a candidate for this study has already started osimertinib within 21 days prior to randomization, the exact osimertinib start date is known, and the patient had the required study baseline imaging completed prior to the osimertinib start date, the patient will be eligible * Patients that have received prior radiation therapy are eligible. Radiation (limited field stereotactic radiation or conventional radiation) must have been completed at least one week prior to study drug initiation and more extensive field radiation (i.e., whole-brain radiotherapy \[WBRT\]) must have been completed at least two weeks prior to drug initiation * Patient must not have any risk factors for anti-VEGF administration, specifically, hemoptysis, active cardiovascular disease, uncontrolled hypertension, significant proteinuria (screening urinalysis \> 300 mg/dl) and tumor invading major blood vessels * Patient must have measurable disease. Baseline measurements of sites of disease must be obtained within 4 weeks prior to study randomization. If a potential target lesion is previously irradiated without subsequent growth and/or is radiated after the imaging from which baseline measurements are obtained, they cannot be included as target lesions, and additional target lesions are required to meet criteria for measurable disease * Patient must not have had any prior systemic treatment for metastatic disease * Patient must be ≥ 18 years of age * Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 * Patient must not be pregnant or breast-feeding due to the potential harm to an unborn fetus and possible risk for adverse events in nursing infants with the treatment regimens being used * All females of childbearing potential must have a blood test or urine study within 14 days prior to randomization to rule out pregnancy * A female of childbearing potential is defined as any woman, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: 1) has achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy; or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months) * Patient of childbearing potential and sexually active males must not expect to conceive or father children by using accepted and effective method(s) of contraception or by abstaining from sexual intercourse for 2 weeks prior to the start of treatment, while on study treatment, and for * 6 weeks after the last dose of protocol treatment for female patients on the osimertinib (AZD9291) alone arm * 4 months after the last dose of protocol treatment for male patients on osimertinib (AZD9291) alone arm * 6 months after the last dose of protocol treatment for all patients on osimertinib (AZD9291) plus bevacizumab combination arm * NOTE: Female patients should also not breastfeed while on treatment and for 6 months after the last dose bevacizumab * Leukocytes \>= 3,000/mcL (obtained =\< 14 days prior to randomization) * Absolute neutrophil count \>= 1,500/mcL (obtained =\< 14 days prior to randomization) * Platelets \>= 100,000/mcL (obtained =\< 14 days prior to randomization) * Hemoglobin \>= 9 g/dL (obtained =\< 14 days prior to randomization) * Total bilirubin and creatinine =\< 1.5 x institutional upper limit of normal (ULN) (obtained =\< 14 days prior to randomization) * Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 x institutional ULN (obtained =\< 14 days prior to randomization) * Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial * For patients with evidence of chronic hepatitis B virus (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 * Patients with treated brain metastases are eligible if neurologically stable without glucocorticoid therapy after the stated washout period from radiation therapy (RT) or surgery provided the metastatic lesions are non-hemorrhagic * Patients with untreated brain metastases or leptomeningeal disease are eligible if the treating physician determines that immediate CNS specific treatment is not required provided the metastatic lesions are non-hemorrhagic and are neurologically stable without glucocorticoid therapy * 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 known history or current symptoms of cardiac disease, 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 * Patient must have the ability to understand and the willingness to sign a written informed consent document and comply with study requirements * Patient must not have had treatment with any investigational drug within five half-lives or 3 months (whichever is greater), prior to study initiation * Patient must not be currently receiving (or unable to stop use prior to receiving the first dose of study treatment) medications or herbal supplements known to be strong inducers of CYP3A4. For any patient currently receiving such inducers of CYP3A4, they must discontinue use prior to first dose of study treatment. All patients must try to avoid concomitant use of any medications, herbal supplements and/or ingestion of foods with known inducer effects on CYP3A4 * Patient must not have any unresolved toxicities from prior therapy greater than Common Terminology Criteria for Adverse Events (CTCAE) grade 1 at the time of randomization, with the exception of alopecia and grade 2 prior platinum-therapy-related neuropathy * Patient must not have any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension and active bleeding diatheses, which in the investigator's opinion makes it challenging for the patient to participate in the study. Screening for chronic conditions is not required * Patient must not have refractory nausea and vomiting, chronic gastrointestinal diseases, the inability to swallow the osimertinib tablets or previous significant bowel resection that would preclude adequate absorption of osimertinib * Patient must not have a medical history of interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonitis which required steroid treatment, or any evidence of clinically active interstitial lung disease * Patient must not have a history of hypersensitivity to active or inactive excipients of osimertinib or drugs with a similar chemical structure or class to osimertinib * Patient must not have mean resting corrected QT interval (QTc) \> 470 msec obtained from 3 electrocardiograms (ECGs), using the screening clinic ECG machine derived QTc value (using Bazett's correction) * Patient must not have any clinically important abnormalities in rhythm, conduction or morphology of resting ECG e.g. complete left bundle branch block, third degree heart block and second-degree heart block * Patient must not have any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, electrolyte abnormalities (including: potassium \< lower limit of normal \[LLN\]; magnesium \< LLN; calcium \< LLN), congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age in first degree relatives or any concomitant medication known to prolong the QT interval and cause torsades de pointes

Elegibilidad en frases sencillas

Los criterios de este registro aún no se han desglosado en frases separadas. El texto del registro anterior está completo y es la versión autorizada.

Diseño del estudio

Diseño del estudio
Tipo de estudio	De intervención
Fase	Fase 3
Asignación	Aleatorizado
Modelo de intervención	PARALLEL
Propósito principal	TREATMENT
Enmascaramiento	NONE (0)
Inscripción	300 participantes buscados

Patrocinador y colaboradores

National Cancer Institute (NCI) Patrocinador

Grupos e intervenciones

Arm A (osimertinib)ACTIVE_COMPARATOR
Patients receive osimertinib PO QD on days 1-21. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients undergo ECHO, MUGA, CT and may undergo MRI and blood and urine sample collection on study.
Arm B (osimertinib, bevacizumab)EXPERIMENTAL
Patients receive osimertinib PO QD on days 1-21 and bevacizumab IV over 30-90 minutes on day 1. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients undergo ECHO, MUGA, CT and may undergo MRI and blood and urine sample collection on study.

Intervenciones

Biológico Bevacizumab
Given IV
Procedimiento Biospecimen Collection
Undergo blood and urine sample collection
Procedimiento Computed Tomography
Undergo CT
Procedimiento Echocardiography Test
Undergo ECHO
Procedimiento Magnetic Resonance Imaging
Undergo MRI
Procedimiento Multigated Acquisition Scan
Undergo MUGA
Fármaco Osimertinib
Given PO

Variables de resultado

Variable de resultado principal
Progression-free survival (PFS)
Will be estimated using the Kaplan-Meier method, and Cox proportional hazards models will be used to estimate the treatment hazard ratios. PFS will use a logrank test stratified on the randomization stratification factors with a one-sided type I error rate of 2.5%.
Plazo From randomization to documented disease progression per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 or death from any cause, whichever occurs first, assessed up to 10 years
Variable de resultado secundaria
Overall survival (OS)
Will be estimated using the Kaplan-Meier method, and Cox proportional hazards models will be used to estimate the treatment hazard ratios. OS will be tested at the one-sided 10% level.
Plazo From randomization to death from any cause, assessed up to 10 years
Variable de resultado secundaria
Best objective response rate
Best objective response will be evaluated via RECIST 1.1 criteria. Will be compared using Fisher's exact tests with a one-sided type I error rate of 2.5%; multivariable logistic regression modeling will be used to adjust for the effect of any covariates that are associated with these categorical outcomes.
Plazo Up to 10 years
Variable de resultado secundaria
Time to central nervous system progression
Will be estimated using competing risks methodology, adjusting for death and progression as competing events. Regular central nervous system imaging will occur when patients are on treatment. After they discontinue study treatment, central nervous system imaging will be symptom-prompted during follow up.
Plazo From study randomization to evidence of central nervous system progressive disease, with death and progression as competing events, assessed up to 10 years
Variable de resultado secundaria
Central nervous system progression-free survival
Will be estimated using the Kaplan-Meier method.
Plazo From study randomization to evidence of central nervous system progressive disease or death from any cause, whichever occurs first, assessed up to 10 years
Variable de resultado secundaria
Incidence of adverse events
Toxicity will be determined using the Common Terminology Criteria for Adverse Events (CTCAE). Will be compared using Fisher's exact tests with a one-sided type I error rate of 2.5%; multivariable logistic regression modeling will be used to adjust for the effect of any covariates that are associated with these categorical outcomes.
Plazo Up to 30 days after the last administration of investigational agent
Otra variable de resultado
Mechanisms of resistance to AZD9291 (osimertinib) and AZD9291 (osimertinib) with bevacizumab first-line therapy through post-progression circulating tumor-derived deoxyribonucleic acid (ctDNA)
Preliminary analyses of these data will utilize tests for association comparing the frequency of a particular genomic aberration at baseline and at progression (for example, using McNemar's test) and association between alterations and baseline characteristics (for example, using Fisher's exact test). More sophisticated analyses may include multivariable logistic regression modeling and/or competing risks analysis.
Plazo Up to 10 years
Otra variable de resultado
Circulating tumor deoxyribonucleic acid (ctDNA) clearance on study treatment
Will assess ctDNA clearance on study treatment and associate ctDNA clearance with clinical outcomes. Cox regression analysis will be used to assess whether EGFR ctDNA clearance is an independent predictor for PFS (and OS), adjusted by treatment effect, the presence of brain metastasis (yes versus \[vs.\] no), EGFR exon 19 deletion/L858R vs other, Eastern Cooperative Oncology Group (ECOG) performance status (0-1 vs 2) and other possible clinical and biological risk factors.
Plazo Up to 10 years

Fechas

Fechas
Fecha de inicio	28 de diciembre de 2020 (real)
Finalización principal	31 de diciembre de 2026 (estimada)
Finalización	31 de diciembre de 2026 (estimada)
Primera publicación	29 de noviembre de 2019 (real)
Última actualización	10 de septiembre de 2026
Resultados publicados	No indicado en el registro
Estado verificado por última vez	mayo de 2026

Real significa que el evento ocurrió. Estimada significa que el patrocinador lo prevé. Ambas cosas significan algo distinto.

Ubicaciones

326 centros están en reclutamiento

United States

United States
Centro	Ciudad	Estado o región	Estado
Providence Regional Cancer System-Aberdeen	Aberdeen	Washington	Suspendido
Hickman Cancer Center	Adrian	Michigan	Suspendido
New Mexico Oncology Hematology Consultants	Albuquerque	New Mexico	Suspendido
University of New Mexico Cancer Center	Albuquerque	New Mexico	En reclutamiento
Lehigh Valley Hospital-Cedar Crest	Allentown	Pennsylvania	En reclutamiento
OSF Saint Anthony's Health Center	Alton	Illinois	Suspendido
Mary Greeley Medical Center	Ames	Iowa	En reclutamiento
McFarland Clinic - Ames	Ames	Iowa	En reclutamiento
Community Hospital of Anaconda	Anaconda	Montana	En reclutamiento
Alaska Women's Cancer Care	Anchorage	Alaska	Suspendido
Anchorage Oncology Centre	Anchorage	Alaska	Suspendido
Katmai Oncology Group	Anchorage	Alaska	En reclutamiento
Providence Alaska Medical Center	Anchorage	Alaska	Suspendido
Alaska Breast Care and Surgery LLC	Anchorage	Alaska	Suspendido
Anchorage Radiation Therapy Center	Anchorage	Alaska	Suspendido
Anchorage Associates in Radiation Medicine	Anchorage	Alaska	Suspendido
Alaska Oncology and Hematology LLC	Anchorage	Alaska	En reclutamiento
UI Health Care Mission Cancer and Blood - Ankeny Clinic	Ankeny	Iowa	En reclutamiento
Trinity Health Saint Joseph Mercy Hospital Ann Arbor	Ann Arbor	Michigan	En reclutamiento
Kaiser Permanente-Deer Valley Medical Center	Antioch	California	En reclutamiento
ThedaCare Regional Cancer Center	Appleton	Wisconsin	En reclutamiento
Mission Hope Medical Oncology - Arroyo Grande	Arroyo Grande	California	Suspendido
Emory University Hospital Midtown	Atlanta	Georgia	En reclutamiento
Emory University Hospital/Winship Cancer Institute	Atlanta	Georgia	En reclutamiento
The Medical Center of Aurora	Aurora	Colorado	Suspendido
Rush-Copley Medical Center	Aurora	Illinois	En reclutamiento
Rocky Mountain Cancer Centers-Aurora	Aurora	Colorado	En reclutamiento
UH Seidman Cancer Center at UH Avon Health Center	Avon	Ohio	En reclutamiento
Saint Alphonsus Cancer Care Center-Baker City	Baker City	Oregon	Suspendido
Mercy Oncology and Hematology - Clayton-Clarkson	Ballwin	Missouri	Suspendido
CommonSpirit Saint Joseph Hospital - Bardstown	Bardstown	Kentucky	Suspendido
Memorial Sloan Kettering Basking Ridge	Basking Ridge	New Jersey	En reclutamiento
Houston Methodist San Jacinto Hospital	Baytown	Texas	En reclutamiento
UHHS-Chagrin Highlands Medical Center	Beachwood	Ohio	En reclutamiento
Indu and Raj Soin Medical Center	Beavercreek	Ohio	Suspendido
PeaceHealth Saint Joseph Medical Center	Bellingham	Washington	Suspendido
Strecker Cancer Center-Belpre	Belpre	Ohio	En reclutamiento
Sanford Joe Lueken Cancer Center	Bemidji	Minnesota	Activo, sin reclutar
Saint Charles Health System	Bend	Oregon	En reclutamiento
ThedaCare Cancer Care - Berlin	Berlin	Wisconsin	En reclutamiento
Walter Reed National Military Medical Center	Bethesda	Maryland	Suspendido
Lehigh Valley Hospital - Muhlenberg	Bethlehem	Pennsylvania	En reclutamiento
Beverly Hospital	Beverly	Massachusetts	Activo, sin reclutar
Billings Clinic Cancer Center	Billings	Montana	En reclutamiento
Sanford Bismarck Medical Center	Bismarck	North Dakota	Activo, sin reclutar
Illinois CancerCare-Bloomington	Bloomington	Illinois	En reclutamiento
Saint Elizabeth Boardman Hospital	Boardman	Ohio	Suspendido
Saint Alphonsus Cancer Care Center-Boise	Boise	Idaho	En reclutamiento
Saint Luke's Cancer Institute - Boise	Boise	Idaho	En reclutamiento
Central Care Cancer Center - Bolivar	Bolivar	Missouri	Suspendido

En el registro figuran 553 centros más.

Documentos del estudio

No hay documentos enlazados en este registro.

Cambios a lo largo del tiempo

5 de agosto de 2026
Centro eliminado
1 site removed (603 total)
604603

Registro: ClinicalTrials.gov · NCT########

https://xmedica.io/trials/ctgov/NCT04181060