A Dose-escalation Study to Evaluate the Safety, Tolerability, and Antitumor Activity of MEDI-573 in Subjects With Advanced Solid Tumors
31 октября 2018 г. обновлено: MedImmune LLC
A Phase 1, Multicenter, Open-label, Single-arm, Dose-escalation Study to Evaluate the Safety, Tolerability, and Antitumor Activity of MEDI-573, a Fully Human Monoclonal Antibody Directed Against Insulin-like Growth Factors I and II, in Subjects With Advanced Solid Tumors Refractory to Standard Therapy or for Which No Standard Therapy Exists
Evaluate the safety and tolerability of MEDI-573 in adult subjects with advanced solid tumors refractory to standard therapy or for which no standard therapy exists.
Обзор исследования
Тип исследования
Интервенционный
Регистрация (Действительный)
43
Фаза
- Фаза 1
Контакты и местонахождение
В этом разделе приведены контактные данные лиц, проводящих исследование, и информация о том, где проводится это исследование.
Места учебы
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Arizona
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Scottsdale, Arizona, Соединенные Штаты, 85259
- Research Site
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Florida
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Jacksonville, Florida, Соединенные Штаты, 32224
- Research Site
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Massachusetts
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Boston, Massachusetts, Соединенные Штаты, 02115
- Research Site
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Michigan
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Detroit, Michigan, Соединенные Штаты, 48201
- Research Site
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Minnesota
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Rochester, Minnesota, Соединенные Штаты, 55905
- Research Site
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Pennsylvania
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Philadelphia, Pennsylvania, Соединенные Штаты, 19111
- Research Site
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Критерии участия
Исследователи ищут людей, которые соответствуют определенному описанию, называемому критериям приемлемости. Некоторыми примерами этих критериев являются общее состояние здоровья человека или предшествующее лечение.
Критерии приемлемости
Возраст, подходящий для обучения
От 18 лет до 99 лет (Взрослый, Пожилой взрослый)
Принимает здоровых добровольцев
Нет
Полы, имеющие право на обучение
Все
Описание
Inclusion Criteria:
- Histologically confirmed advanced solid tumor for which no curative or standard therapies exist.
- Karnofsky Performance Status ≥60.
- Adequate hematological function.
- Adequate organ function.
- Women of non-child-bearing potential (defined as being >1 year post-menopausal) or using effective contraception, e.g., use of oral contraceptives with an additional barrier method (since the investigational product may impair the effectiveness of oral contraceptives), double barrier methods (diaphragm with spermicidal gel or condoms with contraceptive foam), Depo-Provera, partner vasectomy, or total abstinence, from the time the informed consent is signed through 30 days after the last dose of MEDI-573. Male subjects with partners of child-bearing potential must be surgically sterile or use contraceptive method as described above from the time of the initiation of MEDI-573 through 30 days after the last dose of MEDI-573.
Exclusion Criteria:
- No prior treatment within 4 weeks of study drug administration.
- No concurrent therapy for treatment of cancer.
- No uncontrolled diabetes.
- New York Heart Association Grade ≥ 2 congestive heart failure.
- History of myocardial infarction, unstable angina, transient ischemic attack or stroke within the previous 6 months prior to study entry.
- Documented brain metastasis.
- Pregnancy or lactation or plans to become pregnant while on study.
- Clinically significant abnormality on ECG.
Учебный план
В этом разделе представлена подробная информация о плане исследования, в том числе о том, как планируется исследование и что оно измеряет.
Как устроено исследование?
Детали дизайна
- Основная цель: Уход
- Распределение: Н/Д
- Интервенционная модель: Одногрупповое задание
- Маскировка: Нет (открытая этикетка)
Оружие и интервенции
Группа участников / Армия |
Вмешательство/лечение |
|---|---|
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Экспериментальный: MEDI-573 0.5 mg/Kg QWk Dose Escalation
Participants received MEDI-573 0.5 milligram per kilogram (mg/kg) as a 60-minute intravenous (IV) infusion once every 7 days until unacceptable toxicity, documentation of disease progression, or other reason for participant withdrawal.
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Administered at a dose determined by the subject's enrollment cohort as an IV infusion as part of a 21 day treatment cycle.
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Экспериментальный: MEDI-573 1.5 mg/Kg QWk Dose Escalation
Participants received MEDI-573 1.5 mg/kg as a 60-minute IV infusion once every 7 days until unacceptable toxicity, documentation of disease progression, or other reason for participant withdrawal.
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Administered at a dose determined by the subject's enrollment cohort as an IV infusion as part of a 21 day treatment cycle.
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Экспериментальный: MEDI-573 5 mg/Kg QWk Dose Escalation
Participants received MEDI-573 5 mg/kg as a 60-minute IV infusion once every 7 days until unacceptable toxicity, documentation of disease progression, or other reason for participant withdrawal.
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Administered at a dose determined by the subject's enrollment cohort as an IV infusion as part of a 21 day treatment cycle.
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Экспериментальный: MEDI-573 10 mg/Kg QWk Dose Escalation
Participants received MEDI-573 10 mg/kg as a 60-minute IV infusion once every 7 days until unacceptable toxicity, documentation of disease progression, or other reason for participant withdrawal.
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Administered at a dose determined by the subject's enrollment cohort as an IV infusion as part of a 21 day treatment cycle.
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Экспериментальный: MEDI-573 15 mg/Kg QWk Dose Escalation
Participants received MEDI-573 15 mg/kg as a 60-minute IV infusion once every 7 days until unacceptable toxicity, documentation of disease progression, or other reason for participant withdrawal.
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Administered at a dose determined by the subject's enrollment cohort as an IV infusion as part of a 21 day treatment cycle.
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Экспериментальный: MEDI-573 30 mg/Kg Q3Wk Dose Escalation
Participants received MEDI-573 30 mg/kg as a 90-minute IV infusion once every 21 days until unacceptable toxicity, documentation of disease progression, or other reason for participant withdrawal.
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Administered at a dose determined by the subject's enrollment cohort as an IV infusion as part of a 21 day treatment cycle.
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Экспериментальный: MEDI-573 45 mg/Kg Q3Wk Dose Escalation
Participants received MEDI-573 45 mg/kg as a 90-minute IV infusion once every 21 days until unacceptable toxicity, documentation of disease progression, or other reason for participant withdrawal.
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Administered at a dose determined by the subject's enrollment cohort as an IV infusion as part of a 21 day treatment cycle.
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Экспериментальный: MEDI-573 5 mg/Kg QWk Dose Expansion
Participants received MEDI-573 5 mg/kg as a 60-minute IV infusion once every 7 days until unacceptable toxicity, documentation of disease progression, or other reason for participant withdrawal.
|
Administered at a dose determined by the subject's enrollment cohort as an IV infusion as part of a 21 day treatment cycle.
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Экспериментальный: MEDI-573 15 mg/Kg QWk Dose Expansion
Participants received MEDI-573 15 mg/kg as a 60-minute IV infusion once every 7 days until unacceptable toxicity, documentation of disease progression, or other reason for participant withdrawal.
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Administered at a dose determined by the subject's enrollment cohort as an IV infusion as part of a 21 day treatment cycle.
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Что измеряет исследование?
Первичные показатели результатов
Мера результата |
Мера Описание |
Временное ограничение |
|---|---|---|
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Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (SAEs)
Временное ограничение: From the start of study treatment through 30 days after the last dose of MEDI-573, up to 3.5 years
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AEs were any unfavorable and unintended signs (including abnormal laboratory findings), symptoms, or diseases temporally associated with the use of MEDI-573, whether or not considered related to MEDI-573.
A SAE was any AE that resulted in: death; inpatient hospitalization or prolongation of existing hospitalization; persistent or significant disability or incapacity; was life-threatening; was a congenital anomaly/birth defect in the offspring of a study participant; or was an important medical event that may not have resulted in death, threatened life, or required hospitalization and that, based on appropriate medical judgment, may have jeopardized the participant and may have required medical or surgical intervention to prevent one of the outcomes above.
TEAEs were defined as AEs present at baseline that worsened in intensity after administration of MEDI-573, or events absent at baseline that emerged after administration of MEDI-573, up to 30 days after the last dose.
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From the start of study treatment through 30 days after the last dose of MEDI-573, up to 3.5 years
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Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs
Временное ограничение: From the start of study treatment through 30 days after the last dose of MEDI-573, up to 3.5 years
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An abnormal laboratory finding that was judged by the investigator to be medically significant was reported as an AE.
TEAEs were defined as events present at baseline that worsened in intensity after administration of MEDI-573, or events absent at baseline that emerged after administration of MEDI-573, for the period extending to 30 days after the last dose.
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From the start of study treatment through 30 days after the last dose of MEDI-573, up to 3.5 years
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Number of Participants With Vital Signs and Physical Findings Abnormalities Reported as TEAEs
Временное ограничение: From the start of study treatment through 30 days after the last dose of MEDI-573, up to 3.5 years
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Vital signs and physical findings included parameters such as heart rate, blood pressure, temperature, and respiratory rate.
TEAEs were defined as events present at baseline that worsened in intensity after administration of MEDI-573 or events absent at baseline that emerged after administration of MEDI-573, for the period extending to 30 days after the last dose.
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From the start of study treatment through 30 days after the last dose of MEDI-573, up to 3.5 years
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Maximum Tolerated Dose (MTD) of MEDI-573
Временное ограничение: Cycle 1 Day 1 through Cycle 1 Day 21
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The MTD was defined as the highest dose that can be safely administered to participants and was determined by the number of participants in each cohort with a dose-limiting toxicity (DLT).
The number and proportion of participants in each dose cohort and the number of participants with a DLT was presented using the total number of participants in the MTD Evaluable Population as the denominator.
2 participants from Cohorts 0.5 and 5 mg/kg QWk (1 in each cohort) did not complete the DLT period and therefore not evaluable for MTD.
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Cycle 1 Day 1 through Cycle 1 Day 21
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Number of Participants With Dose-Limiting Toxicities (DLTs)
Временное ограничение: Cycle 1 Day 1 through Cycle 1 Day 21
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A DLT was defined as any grade greater than or equal to (>=) 3 treatment-related non-hematologic toxicity that occurred during the DLT assessment period with the following exceptions: Grade less than (<) 4 serum-high glucose (fasting) with duration of < 24 hours; Grade 3 fever (in the absence of neutropenia) defined as > 40.0 degree centigrade (°C) [greater than (>) 104.0°F] that resolved to normal or baseline within 24 hours of treatment and was not considered an SAE; or Grade 3 rigors/chills that responded to optimal therapy; any Grade >= 3 treatment-related hematologic toxicity that occurred during the DLT assessment period.
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Cycle 1 Day 1 through Cycle 1 Day 21
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Optimal Biologically Effective Dose (OBED) of MEDI-573
Временное ограничение: From the start of study treatment through 30 days after the last dose of MEDI-573, up to 3.5 years
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The OBED was defined as the dose at which all circulating insulin-like growth factor (IGF)-1 and IGF-2 ligand was sequestered by MEDI-573.
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From the start of study treatment through 30 days after the last dose of MEDI-573, up to 3.5 years
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Вторичные показатели результатов
Мера результата |
Мера Описание |
Временное ограничение |
|---|---|---|
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Maximum Observed Serum Concentration (Cmax) After the First Dose
Временное ограничение: For weekly dosing: Pre- and post-infusion (0, 2, 6, 24, and 48 hours post-infusion); For 3 weekly dosing: Pre- and post-infusion (0, 2, 6, 24, and 48 hours post-infusion); and on Days 8 and 15
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The Cmax was the maximum observed serum concentration of MEDI-573.
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For weekly dosing: Pre- and post-infusion (0, 2, 6, 24, and 48 hours post-infusion); For 3 weekly dosing: Pre- and post-infusion (0, 2, 6, 24, and 48 hours post-infusion); and on Days 8 and 15
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Time to Reach Maximum Observed Concentration (Tmax) After the First Dose
Временное ограничение: For weekly dosing: Pre- and post-infusion (0, 2, 6, 24, and 48 hours post-infusion); For 3 weekly dosing: Pre- and post-infusion (0, 2, 6, 24, and 48 hours post-infusion); and on Days 8 and 15
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The tmax was defined as actual sampling time to reach the maximum observed serum concentration of MEDI-573.
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For weekly dosing: Pre- and post-infusion (0, 2, 6, 24, and 48 hours post-infusion); For 3 weekly dosing: Pre- and post-infusion (0, 2, 6, 24, and 48 hours post-infusion); and on Days 8 and 15
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Trough Serum Concentration (Ctrough) After the First Dose
Временное ограничение: For weekly dosing: Pre- and post-infusion (0, 2, 6, 24, and 48 hours post-infusion); For 3 weekly dosing: Pre- and post-infusion (0, 2, 6, 24, and 48 hours post-infusion); and on Days 8 and 15
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The Ctrough was the lowest serum concentration of MEDI-573 within a dosing interval.
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For weekly dosing: Pre- and post-infusion (0, 2, 6, 24, and 48 hours post-infusion); For 3 weekly dosing: Pre- and post-infusion (0, 2, 6, 24, and 48 hours post-infusion); and on Days 8 and 15
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Dose Normalized Cmax (Cmax/Dose) After the First Dose
Временное ограничение: For weekly dosing: Pre- and post-infusion (0, 2, 6, 24, and 48 hours post-infusion); For 3 weekly dosing: Pre- and post-infusion (0, 2, 6, 24, and 48 hours post-infusion); and on Days 8 and 15
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The Cmax/dose was the dose-normalized maximum serum concentration of MEDI-573.
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For weekly dosing: Pre- and post-infusion (0, 2, 6, 24, and 48 hours post-infusion); For 3 weekly dosing: Pre- and post-infusion (0, 2, 6, 24, and 48 hours post-infusion); and on Days 8 and 15
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Area Under the Serum Concentration-time Curve Over the First Dosing Interval (AUCτ)
Временное ограничение: For weekly dosing: Pre- and post-infusion (0, 2, 6, 24, and 48 hours post-infusion); For 3 weekly dosing: Pre- and post-infusion (0, 2, 6, 24, and 48 hours post-infusion); and on Days 8 and 15
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Area under the serum concentration-time curve over the first dosing interval.
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For weekly dosing: Pre- and post-infusion (0, 2, 6, 24, and 48 hours post-infusion); For 3 weekly dosing: Pre- and post-infusion (0, 2, 6, 24, and 48 hours post-infusion); and on Days 8 and 15
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Dose-normalized Area Under the Serum Concentration Time Curve Over the First Dosing Interval (AUCτ/Dose)
Временное ограничение: For weekly dosing: Pre- and post-infusion (0, 2, 6, 24, and 48 hours post-infusion); For 3 weekly dosing: Pre- and post-infusion (0, 2, 6, 24, and 48 hours post-infusion); and on Days 8 and 15
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The AUCtau/dose was a measure of dose-normalized area under the serum concentration-time curve over the first dosing interval.
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For weekly dosing: Pre- and post-infusion (0, 2, 6, 24, and 48 hours post-infusion); For 3 weekly dosing: Pre- and post-infusion (0, 2, 6, 24, and 48 hours post-infusion); and on Days 8 and 15
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Number of Participants With Positive Anti-Drug Antibodies (ADA) to MEDI-573
Временное ограничение: Pre-infusion on Day 1 of each cycle, end of treatment, and 90 days after last dose MEDI-573 (up to 3.5 years)
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Two methods were used to assess the immunogenicity data: an ECL-based method and measurement of neutralizing ADA.
The titer was calculated by multiplying the minimum assay dilution factor by the reciprocal of the highest dilution factor which yielded an ECL multiple equal to or greater than the screening assay cut-point factor.
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Pre-infusion on Day 1 of each cycle, end of treatment, and 90 days after last dose MEDI-573 (up to 3.5 years)
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Objective Response Rate (ORR)
Временное ограничение: From study entry through the end of the study, up to 3.5 years
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The ORR was defined as the proportion of participants with confirmed complete response (CR) or partial response (PR) according to the RECIST criteria The CR was defined as disappearance of all target and nontarget lesions and no new lesions; and PR was definded as >= 30% decrease in the sum of diameters of Target Lesions (compared to baseline [screening]) and no new lesions.
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From study entry through the end of the study, up to 3.5 years
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Progression-free Survival (PFS)
Временное ограничение: From study entry through the end of the study, up to 3.5 years
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Progression-free survival (PFS) was defined as the duration from the start of treatment with MEDI-573 until the documentation of disease progression or death due to any cause, whichever occurred first.
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From study entry through the end of the study, up to 3.5 years
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Time to Progression
Временное ограничение: From study entry through the end of the study, up to 3.5 years
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Time to disease progression (TTP) was defined as the duration from the start of treatment with MEDI-573 until the documentation of disease progression.
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From study entry through the end of the study, up to 3.5 years
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Overall Survival
Временное ограничение: From study entry through the end of the study, up to 3.5 years
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Overall survival (OS) was defined as the time from the start of treatment with MEDI-573 until death.
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From study entry through the end of the study, up to 3.5 years
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Time to Response (TTR)
Временное ограничение: From study entry through the end of the study, up to 3.5 years
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Time to response was defined as the duration from the start of treatment with MEDI-573 to the first documentation of objective response (confirmed CR or PR) and was only assessed in participants who had achieved objective response.
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From study entry through the end of the study, up to 3.5 years
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Duration of Response
Временное ограничение: From study entry through the end of the study, up to 3.5 years
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Duration of response was defined as the duration from the first documentation of objective response (confirmed CR or PR) to the first documented disease progression.
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From study entry through the end of the study, up to 3.5 years
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Suppression Profiles of IGF-I and IGF-II Post-Administration of MEDI-573
Временное ограничение: From the start of study treatment through 30 days after the last dose of MEDI-573, up to 3.5 years
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The suppression profiles of both IGF-1 and IGF-2 post administration of MEDI-573 in relation to time course of antibody concentrations in serum were evaluated during treatment.
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From the start of study treatment through 30 days after the last dose of MEDI-573, up to 3.5 years
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Соавторы и исследователи
Здесь вы найдете людей и организации, участвующие в этом исследовании.
Спонсор
Следователи
- Директор по исследованиям: Susan Perez, MD, MSc, MedImmune LLC
Публикации и полезные ссылки
Лицо, ответственное за внесение сведений об исследовании, добровольно предоставляет эти публикации. Это может быть что угодно, связанное с исследованием.
Полезные ссылки
Даты записи исследования
Эти даты отслеживают ход отправки отчетов об исследованиях и сводных результатов на сайт ClinicalTrials.gov. Записи исследований и сообщаемые результаты проверяются Национальной медицинской библиотекой (NLM), чтобы убедиться, что они соответствуют определенным стандартам контроля качества, прежде чем публиковать их на общедоступном веб-сайте.
Изучение основных дат
Начало исследования (Действительный)
9 марта 2009 г.
Первичное завершение (Действительный)
11 сентября 2012 г.
Завершение исследования (Действительный)
11 сентября 2012 г.
Даты регистрации исследования
Первый отправленный
23 декабря 2008 г.
Впервые представлено, что соответствует критериям контроля качества
30 декабря 2008 г.
Первый опубликованный (Оценивать)
1 января 2009 г.
Обновления учебных записей
Последнее опубликованное обновление (Действительный)
4 марта 2019 г.
Последнее отправленное обновление, отвечающее критериям контроля качества
31 октября 2018 г.
Последняя проверка
1 октября 2018 г.
Дополнительная информация
Термины, связанные с этим исследованием
Другие идентификационные номера исследования
- MI-CP184
Информация о лекарствах и устройствах, исследовательские документы
Изучает лекарственный продукт, регулируемый FDA США.
Да
Изучает продукт устройства, регулируемый Управлением по санитарному надзору за качеством пищевых продуктов и медикаментов США.
Нет
Эта информация была получена непосредственно с веб-сайта clinicaltrials.gov без каких-либо изменений. Если у вас есть запросы на изменение, удаление или обновление сведений об исследовании, обращайтесь по адресу register@clinicaltrials.gov. Как только изменение будет реализовано на clinicaltrials.gov, оно будет автоматически обновлено и на нашем веб-сайте. .