Sponsor: Celcuity Inc (industry)
Phase: 3
Start date: Dec. 8, 2022
Planned enrollment: 701
Gedatolisib is an investigational drug developed by Celcuity, Inc., targeting the PI3K/AKT/mTOR (PAM) pathway, which is frequently dysregulated in various cancers. It is currently being evaluated in clinical trials for the treatment of advanced breast cancer and other solid tumors.
Gedatolisib is a potent, pan-class I isoform PI3K and mTOR inhibitor. It exhibits low nanomolar potency against all four PI3K isoforms (p110α, p110β, p110γ, and p110δ) and both mTOR complexes (mTORC1 and mTORC2). By simultaneously inhibiting these targets, gedatolisib aims to provide comprehensive blockade of the PAM pathway, potentially overcoming resistance mechanisms associated with isoform-specific inhibitors. (celcuity.com)
Phase 1b Study in HR+/HER2- Advanced Breast Cancer:
In a Phase 1b clinical trial, gedatolisib was combined with palbociclib (a CDK4/6 inhibitor) and endocrine therapy (either fulvestrant or letrozole) in patients with hormone receptor-positive (HR+), HER2-negative advanced breast cancer. The study included both dose escalation and expansion cohorts, enrolling a total of 138 patients. Key findings include:
Median Duration of Response (DOR): 46.9 months (biospace.com)
CDK4/6 Inhibitor-Pretreated Patients:
Phase 2 Study in HER2+ Metastatic Breast Cancer:
An investigator-sponsored Phase 2 trial evaluated gedatolisib in combination with trastuzumab-pkrb in 44 patients with HER2-positive, PIK3CA-mutated metastatic breast cancer. Results showed:
In the Phase 1b study, the combination of gedatolisib with palbociclib and endocrine therapy demonstrated a manageable safety profile. Common adverse events included:
Notably, 80% of participants experienced a Grade 3 or higher adverse event, with dose reductions required in 18 out of 27 patients in one cohort. However, the neutropenia observed was likely attributable to palbociclib, as gedatolisib monotherapy is not associated with myelosuppression. (faileddrugs.com)
In the Phase 2 study for HER2+ metastatic breast cancer, no patients discontinued gedatolisib due to treatment-related adverse events, and only one patient (2.3%) experienced Grade 3 hyperglycemia. (biospace.com)
Note: The information provided is based on data available up to August 3, 2025.
Last updated: Aug 2025
Last updated: Aug 2025
Goal: To evaluate the efficacy and safety of gedatolisib in combination with fulvestrant, with or without palbociclib, versus standard-of-care therapies in patients with HR-positive, HER2-negative advanced or metastatic breast cancer who have progressed on or after prior CDK4/6 inhibitor plus aromatase inhibitor therapy.
Patients: Adults (including premenopausal, postmenopausal women and men) with locally advanced or metastatic HR-positive, HER2-negative breast cancer who have progressed during or after treatment with a CDK4/6 inhibitor and a non-steroidal aromatase inhibitor, with good performance status (ECOG 0-1) and adequate organ function. Key exclusions include prior treatment with PI3K, AKT, or mTOR inhibitors, prior chemotherapy or ADCs in the advanced setting, uncontrolled diabetes, untreated or active CNS metastases, and significant uncontrolled cardiovascular disease.
Design: This is a randomized, open-label, phase 3 trial with subjects stratified by PIK3CA mutation status. Patients are randomized to different treatment arms depending on PIK3CA status and receive either experimental combinations or appropriate standard-of-care comparators. Primary allocation is by randomization, and central review is used for efficacy endpoints.
Treatments: Investigational arms include gedatolisib (an intravenously administered, potent pan-PI3K/mTOR inhibitor targeting all four class I PI3K isoforms and both mTOR complexes) combined with fulvestrant, with or without palbociclib. Gedatolisib aims to achieve comprehensive blockade of the PI3K/AKT/mTOR pathway and has demonstrated encouraging response rates and manageable safety in earlier studies, particularly when used in combination regimens, including ORRs up to 78.8% in treatment-naive populations and 36–63% in CDK4/6-pretreated cohorts. Comparator arms use fulvestrant alone for PIK3CA wild-type patients, and alpelisib plus fulvestrant for those with PIK3CA mutations. Fulvestrant is a standard selective estrogen receptor degrader, and alpelisib is an oral PI3K alpha-selective inhibitor approved for PIK3CA-mutant HR+/HER2- MBC.
Outcomes: The primary endpoint is progression-free survival (PFS) in both PIK3CA mutant and wild-type patient groups, as determined by blinded central review. Secondary endpoints include overall survival, overall response rate, duration of response, time to response, clinical benefit rate, and a range of patient-reported quality of life measures (FACT-B TOI, NFBSI-16, PROMIS, EQ-5D-5L), along with assessment of adverse events and safety profile.
Burden on patient: Patient burden is estimated to be moderate. While the study uses IV administration of gedatolisib, standard imaging, and quality of life assessments, it does not require frequent extra biopsies or specialized pharmacokinetic blood draws typical of early-phase trials. Tumor tissue is required for PIK3CA testing, which can utilize existing archival tissue for most patients. The schedule for safety and efficacy follow-up (imaging, labs, adverse event monitoring) is similar to accepted practice in advanced/metastatic trials. The major additional burden arises from more frequent clinic visits for intravenous administration and monitoring, especially for combination arms.
Inclusion Criteria:
1. Histologically or cytologically confirmed diagnosis of metastatic or locally advanced breast cancer Adult females, pre- and/or post-menopausal, and adult males. Pre-menopausal (and peri-menopausal) women can be enrolled if amenable to treatment with an LHRH agonist. Patients are to have commenced concomitant treatment with LHRH agonist prior to or on Cycle 1, Day 1 and must be willing to continue on it for the duration of the study.
2. Negative pregnancy test for women of childbearing potential. Female subjects of childbearing potential must use an effective and/or acceptable contraceptive method from screening until 1 year after the last dose of study treatment
3. Confirmed diagnosis of estrogen receptor positive and/or progesterone receptor positive, as per American Society of Clinical Oncology/College of American Pathologists (ASCO-CAP) guidelines (2020), based on most recent tumor biopsy utilizing an assay consistent with local standards
4. Documented HER2 immunohistochemistry (IHC) negative as per ASCO-CAP 2018 guidance
5. Adequate archival or fresh tumor tissue for the analysis of PIK3CA mutational status
6. Subject must have documentation of radiological disease progression on or after the last prior treatment and also have radiologically evaluable disease (measurable and/or non-measurable) according to RECIST v1.1, per local assessment. Subjects with bone only disease must have lytic or mixed lytic/blastic lesions that can be accurately assessed; bone only blastic lesions with no soft tissue component is not allowed.
7. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
8. Life expectancy of at least 3 months
9. Progressed during or after CDK4/6 inhibitor combination treatment with non-steroidal aromatase inhibitor (AI)
10. Adequate bone marrow, hepatic, renal and coagulation function
Exclusion Criteria:
1. History of malignancies other than adequately treated non-melanoma skin cancer, curatively treated in situ cancer of the cervix, or other solid tumors curatively treated with no evidence of disease for ≥3 years
2. Prior treatment with a phosphoinositide 3-kinase (PI3K) inhibitor, a protein kinase B (Akt) inhibitor, or a mechanistic target of rapamycin (mTOR) inhibitor
3. Prior treatment with chemotherapy and antibody drug conjugates for advanced disease is not permitted (prior adjuvant or neoadjuvant chemotherapy is permitted)
4. More than 2 lines of prior endocrine therapy treatment
5. Bone only disease that is only blastic with no soft tissue component
6. Subjects with type 1 diabetes or uncontrolled type 2 diabetes
7. Known and untreated, or active, brain or leptomeningeal metastases
a. Subjects with previously treated central nervous system (CNS) metastases may be enrolled in the study if they meet the following criteria: do not require supportive therapy with steroids; do not have seizures and do not exhibit uncontrolled neurological symptoms; stable disease confirmed by radiographic assessment within at least 4 weeks prior to enrollment
8. Patients with advanced, symptomatic, visceral spread that are at risk of life-threatening complication in the short-term
9. History of clinically significant cardiovascular abnormalities such as: Congestive heart failure (New York Heart Association (NYHA) classification ≥ II within 6 months of study entry
1. Myocardial infarction within 12 months of study entry
2. History of any uncontrolled (or untreated) clinically significant cardiac arrhythmias, (e.g., ventricular tachycardia), complete left bundle branch block, high grade AV block (e.g., bifascicular block, Mobitz type II and third degree AV block), supraventricular, nodal arrhythmias, or conduction abnormality in the previous 12 months
3. Uncontrolled hypertension defined by systolic blood pressure (SBP) ≥160 mmHg and/or diastolic blood pressure (DBP) ≥100 mmHg, with or without antihypertensive medication (initiation or adjustment of antihypertensive medication\[s\] is allowed prior to screening)
4. Long QT syndrome, family history of idiopathic sudden death or congenital long QT syndrome, or any of the following:
* i. Risk factors for Torsades de Pointes (TdP) including uncorrected hypokalemia or hypomagnesemia, or history of clinically significant/symptomatic bradycardia
* ii. On screening, inability to determine the corrected QT interval using Fridericia's formula (QTcF) on the ECG (i.e., unreadable or not interpretable) or QTcF \>480 msec (determined by mean of triplicate ECGs at screening)
10. Known hypersensitivity to the study drugs or their components
11. Pregnant or breast-feeding women
12. Concurrent participation in another interventional clinical trial
1. Subjects must agree not to participate in another clinical trial (other than observational) at any time during participation in VIKTORIA-1.
San Juan, Argentina
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Salta, Argentina
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Paraná, Argentina
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Córdoba, Argentina
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Buenos Aires, Argentina
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Buenos Aires, Argentina
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Buenos Aires, Argentina
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Buenos Aires, Argentina
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Buenos Aires, Argentina
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Buenos Aires, Argentina
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Buenos Aires, Argentina
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Tucumán, Argentina
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Santa Fe, Argentina
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Woodville, Australia
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Wahroonga, Australia
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Southport, Australia
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South Brisbane, Australia
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Nedlands, Australia
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Frankston, Australia
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Status: Completed
Fitzroy, Australia
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Adelaide, Australia
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Vienna, Austria
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Vienna, Austria
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St. Poelten, Austria
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Salzburg, Austria
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Linz, Austria
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Innsbruck, Austria
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Graz, Austria
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Yvoir, Belgium
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Sint-Niklaas, Belgium
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Liège, Belgium
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Leuven, Belgium
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Kortrijk, Belgium
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Edegem, Belgium
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Charleroi, Belgium
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Brussels, Belgium
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Verviers, Belgium
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Belém, Pará, Brazil
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Salvador de Bahia, Brazil
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São Paulo, Brazil
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São Paulo, Brazil
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Minas Gerais, Brazil
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Ijuí, Brazil
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Fortaleza, Brazil
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Sofia, Bulgaria
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Varna, Bulgaria
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Panagyurishte, Bulgaria
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Sofia, Bulgaria
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Sofia, Bulgaria
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Vancouver, British Columbia, Canada
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Status: Not yet recruiting
Chicoutimi, Quebec, Canada
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Status: Recruiting
Montréal, Quebec, Canada
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Status: Not yet recruiting
Montréal, Quebec, Canada
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Status: Recruiting
Prague, Czechia
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Prague, Czechia
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Olomouc, Czechia
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Prague, Czechia
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La Roche-sur-Yon, 85925, France
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Villejuif, France
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Strasbourg, France
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Poitiers, France
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Marseille, France
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Caen, 14076, France
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Bordeaux, France
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Bayreuth, Germany
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Berlin, Germany
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Luebeck, Germany
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Mainz, Germany
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Mecklenburg, Germany
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Münster, Germany
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Saarbrücken, Germany
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Wuppertal, Germany
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Athens, Greece
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Ioánnina, Greece
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Larissa, Greece
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Thessaloníki, Greece
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Thessaloníki, Greece
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Debrecen, Hungary
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Kecskemét, Hungary
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Nyíregyháza, Hungary
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Status: Recruiting
Bangalore, India
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Status: Not yet recruiting
Chandigarh, India
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Status: Not yet recruiting
Kolkata, India
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Status: Completed
Navi Mumbai, India
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Status: Completed
Vellore, India
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Status: Not yet recruiting
Milan, Italy
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Status: Recruiting
Modena, Italy
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Monza, Italy
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Parma, Italy
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Prato, Italy
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Rome, Italy
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Rome, Italy
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Udine, Italy
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Soeul, Korea, Republic of
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Ulsan, Korea, Republic of
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Soeul, Korea, Republic of
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Soeul, Korea, Republic of
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Soeul, Korea, Republic of
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Seoul, Korea, Republic of
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Status: Recruiting
Nuevo León, Mexico
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Status: Recruiting
Querétaro, Mexico
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Status: Completed
Saltillo, Mexico
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Status: Recruiting
Mexico City, Mexico
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Status: Recruiting
Mexico City, Mexico
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Mexico City, Mexico
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Monterrey, 64460, Mexico
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Morelia, Mexico
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Nuevo León, Mexico
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Status: Recruiting
Konin, Poland
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Kraków, Poland
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Opole, Poland
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Siedlce, Poland
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Szczecin, Poland
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Warsaw, Poland
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Warsaw, Poland
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Wroclaw, Poland
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Łódź, Poland
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Bydgoszcz, Poland
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Cluj-Napoca, Romania
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Status: Completed
Baia Mare, Romania
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Bucharest, Romania
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Craiova, Romania
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Craiova, Romania
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Târgu-Mureş, Romania
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Singapore, Singapore
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Singapore, Singapore
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Singapore, Singapore
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Singapore, Singapore
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Singapore, Singapore
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Cáceres, Spain
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Barcelona, Spain
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Badajoz, Spain
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Santiago De Compostela, Spain
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Murcia, Spain
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Madrid, Spain
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Madrid, Spain
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Tainan, Taiwan
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New Taipei City, Taiwan
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Status: Not yet recruiting
Kaohsiung, Taiwan
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Status: Recruiting
Taipei, Taiwan
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Status: Not yet recruiting
Taipei, Taiwan
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Status: Recruiting
Taichung, Taiwan
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Status: Not yet recruiting
Cardiff, United Kingdom
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Status: Not yet recruiting
Bath, United Kingdom
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Status: Not yet recruiting
Nottingham, United Kingdom
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Status: Not yet recruiting
Manchester, United Kingdom
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Status: Not yet recruiting
London, United Kingdom
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Status: Not yet recruiting
London, United Kingdom
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Status: Not yet recruiting
Birmingham, Alabama, 35294, United States
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Status: Recruiting
Goodyear, Arizona, 85395, United States
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Status: Completed
Jonesboro, Arkansas, 72401, United States
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Status: Recruiting
Little Rock, Arkansas, 72205, United States
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Status: Recruiting
Whittier, California, 90602-1006, United States
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Status: Completed
Anaheim, California, 92801, United States
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Status: Completed
Harbor City, California, 90710, United States
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Status: Completed
Los Alamitos, California, 90720, United States
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Status: Recruiting
Monterey, California, 93940, United States
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Status: Recruiting
Orange, California, 92868, United States
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Status: Recruiting
Oxnard, California, 93030, United States
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Status: Completed
Redlands, California, 92373, United States
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Status: Recruiting
Santa Monica, California, 90904, United States
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Status: Recruiting
Torrance, California, 90505, United States
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Status: Recruiting
Vallejo, California, 94589, United States
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Status: Recruiting
New Haven, Connecticut, 06520-8028, United States
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Status: Recruiting
Jacksonville, Florida, 32256, United States
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Status: Recruiting
Winter Haven, Florida, 33881, United States
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Status: Completed
Tampa, Florida, 33612, United States
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Status: Recruiting
Hollywood, Florida, 33021, United States
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Status: Recruiting
Thomasville, Georgia, 31792, United States
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Status: Recruiting
Arlington Heights, Illinois, 60005, United States
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Status: Recruiting
Fort Wayne, Indiana, 46845, United States
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Status: Recruiting
Lexington, Kentucky, 40536-0293, United States
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Status: Recruiting
Paducah, Kentucky, 42003, United States
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Status: Recruiting
Rockville, Maryland, 20850, United States
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Status: Recruiting
Bethesda, Maryland, 20817-7847, United States
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Status: Recruiting
Boston, Massachusetts, 02215, United States
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Status: Recruiting
Boston, Massachusetts, 02215-5450, United States
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Status: Recruiting
Detroit, Michigan, 48202, United States
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Status: Recruiting
Omaha, Nebraska, 68130, United States
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Status: Recruiting
Lincoln, Nebraska, 68506, United States
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Status: Recruiting
Omaha, Nebraska, 68198, United States
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Status: Completed
Syracuse, New York, 13057, United States
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Status: Recruiting
Albany, New York, 12206, United States
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Status: Recruiting
Bronx, New York, 10467, United States
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Status: Recruiting
Jamaica, New York, 11432, United States
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Status: Recruiting
New York, New York, 10021-5302, United States
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Status: Recruiting
New York, New York, 10021, United States
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Status: Recruiting
Rochester, New York, 14642, United States
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Status: Not yet recruiting
White Plains, New York, 10601, United States
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Status: Recruiting
Greensboro, North Carolina, 27403, United States
No email / No phone
Status: Recruiting
Lumberton, North Carolina, 28359, United States
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Status: Recruiting
Cleveland, Ohio, 44106-1716, United States
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Status: Recruiting
Columbus, Ohio, 43210, United States
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Status: Recruiting
Oklahoma City, Oklahoma, 73104, United States
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Status: Recruiting
Tigard, Oregon, 97223, United States
No email / No phone
Status: Completed
Salem, Oregon, 97301, United States
No email / No phone
Status: Recruiting
York, Pennsylvania, 17403, United States
No email / No phone
Status: Completed
Broomall, Pennsylvania, 19008, United States
No email / No phone
Status: Completed
Horsham, Pennsylvania, 19044, United States
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Status: Recruiting
Sioux Falls, South Dakota, 57104, United States
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Status: Recruiting
Houston, Texas, 78234, United States
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Status: Recruiting
McKinney, Texas, 75071, United States
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Status: Completed
Tyler, Texas, 75702, United States
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Status: Recruiting
Sugar Land, Texas, 77479, United States
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Status: Recruiting
Austin, Texas, 78745, United States
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Status: Recruiting
Dallas, Texas, 75230, United States
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Status: Completed
Dallas, Texas, 75246, United States
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Status: Recruiting
El Paso, Texas, 79920, United States
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Status: Recruiting
Houston, Texas, 77030, United States
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Status: Recruiting
Houston, Texas, 77030, United States
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Status: Recruiting
Roanoke, Virginia, 24014, United States
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Status: Recruiting
Fort Belvoir, Virginia, 22060, United States
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Status: Recruiting
Midlothian, Virginia, 23114, United States
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Status: Recruiting
Richmond, Virginia, 23219, United States
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Status: Recruiting
Newport News, Virginia, 23502, United States
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Status: Recruiting
Tacoma, Washington, 98405, United States
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Status: Recruiting
Seattle, Washington, 98109-1023, United States
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Status: Recruiting