A Phase 1 Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of MEDI0639 in Advanced Solid Tumors
2017년 3월 21일 업데이트: MedImmune LLC
A Phase 1, Multicenter, Open-label Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of MEDI0639 in Adult Subjects With Advanced Solid Tumors
This is a first-time-in-human, Phase 1, multicenter, open-label, single-arm, dose-escalation (3+3) study to evaluate the safety, tolerability, antitumor activity, PK and immunogenicity of MEDI0639.
연구 개요
상세 설명
This is a first-time-in-human, Phase 1, multicenter, open-label, single-arm, dose-escalation (3+3) study to evaluate the safety, tolerability, antitumor activity, PK, and immunogenicity of MEDI0639 in adult subjects with advanced solid tumors refractory to standard therapy or for which no standard therapy exist.
Up to 63 subjects will be enrolled at approximately 3 to 5 study centers in North America.
연구 유형
중재적
등록 (실제)
58
단계
- 1단계
연락처 및 위치
이 섹션에서는 연구를 수행하는 사람들의 연락처 정보와 이 연구가 수행되는 장소에 대한 정보를 제공합니다.
연구 장소
-
-
California
-
Los Angeles, California, 미국, 90404
- Research Site
-
-
Connecticut
-
New Haven, Connecticut, 미국, 06513
- Research Site
-
-
Massachusetts
-
Boston, Massachusetts, 미국
- Research Site
-
-
Michigan
-
Ann Arbor, Michigan, 미국, 48103
- Research Site
-
-
Minnesota
-
Minneapolis, Minnesota, 미국
- Research Site
-
-
New York
-
New York, New York, 미국, 10002
- Research Site
-
-
Ohio
-
Cincinnati, Ohio, 미국, 45201
- Research Site
-
Cleveland, Ohio, 미국, 44105
- Research Site
-
-
Texas
-
Houston, Texas, 미국, 77030
- Research Site
-
-
Washington
-
Seattle, Washington, 미국, 98112
- Research Site
-
Tacoma, Washington, 미국, 98405
- Research Site
-
-
참여기준
연구원은 적격성 기준이라는 특정 설명에 맞는 사람을 찾습니다. 이러한 기준의 몇 가지 예는 개인의 일반적인 건강 상태 또는 이전 치료입니다.
자격 기준
공부할 수 있는 나이
18년 (성인, 고령자)
건강한 자원 봉사자를 받아들입니다
아니
연구 대상 성별
모두
설명
Inclusion Criteria:
- Histologically or cytologically confirmed solid tumors that are refractory to standard therapy or for which no standard therapy exist
- Age ≥ 18 years
- ECOG Performance Status of 0 or 1
- LVEF (measured by Echocardiogram) > 50%
- No gastrointestinal bleeding within 1 year of study entry.
Adequate organ and marrow function:
- Hemoglobin ≥ 10g/dL
- Absolute Neutrophil Count ≥ 1500/mm3
- Platelet Count ≥ 100,000/mm3
- AST & ALT ≤ 2.5 x ULN
- Bilirubin ≤ 1.5 x ULN
- Cr Cl ≥ 50 mL/min (as determined by the Cockcroft-Gault equation or by 24-hour urine collection)
- Prior therapy against VEGF or VEGFRs including, but not limited to bevacizumab, sunitinib, sorafenib, pazopanib, motesanib (AMG706), or cediranib (AZD2171), is permitted so long as the agent does not have any known activity against DLL4 and the last dose received s at least 6 weeks prior to first dose of MEDI0639.
- Life expectancy ≥ 12 weeks
- Females of childbearing potential must be surgically sterile, have a sterile male partner, be premenarchal or at least 2 years postmenopausal, practice abstinence or otherwise must use 2 effective methods of contraception from the time of initiation of investigational product.
- Males, unless surgically sterile, must use 2 effective methods of contraception with a female partner and must agree to continue using such contraception for 90 days after the last dose of MEDI0639
Exclusion Criteria:
- Concurrent enrollment in another investigational clinical study
- Receipt of any investigational anticancer therapy within 4 weeks prior to the first dose of MEDI0639 or in the case of monoclonal antibodies, 6 weeks prior to the first dose of MEDI0639
- Concurrent or previous treatment with inhibitors of DLL4
- Any concurrent chemotherapy, radiotherapy, immunotherapy, biologic or hormonal therapy for cancer treatment
- Known bleeding diathesis, esophageal varices, or angioplasty
- Pulmonary hemorrhage or gross hemoptysis within 12 months
- Known arterial or venous thrombosis or pulmonary embolism within 2 years
- Concurrent use of systemic low molecular weight heparin or low dose warfarin
- Presence of brain metastases
- Cerebrovascular accident or transient ischemic attack within 2 years
- Cardiovascular events, such as myocardial infarction, unstable/severe angina, coronary/peripheral artery bypass graft, unstable cardiac arrhythmia requiring medication, congestive heart failure (NYHA > class II), within 2 years
- Tumors with squamous cell histology
- Major surgical procedure within 90 days
- Pregnancy or lactation
- Known HIV positive or Hepatitis A, B, or C infection
공부 계획
이 섹션에서는 연구 설계 방법과 연구가 측정하는 내용을 포함하여 연구 계획에 대한 세부 정보를 제공합니다.
연구는 어떻게 설계됩니까?
디자인 세부사항
- 주 목적: 치료
- 할당: 해당 없음
- 중재 모델: 단일 그룹 할당
- 마스킹: 없음(오픈 라벨)
무기와 개입
참가자 그룹 / 팔 |
개입 / 치료 |
|---|---|
|
실험적: MEDI0639 Cohort 1
Participants received MEDI0639 dose level 1 as a 60-minute intravenous (IV) infusion on Day 1 of each 21-day cycle.
|
MEDI0639 is an immunoglobulin G1 lambda (IgG1λ) monoclonal antibody.
MEDI0639 selectively binds to DLL4 and blocks its ability to bind to and activate signaling through the Notch receptors.
|
|
실험적: MEDI0639 Cohort 2
Participants received MEDI0639 dose level 2 as a 60-minute IV infusion on Day 1 of each 21-day cycle.
|
MEDI0639 is an immunoglobulin G1 lambda (IgG1λ) monoclonal antibody.
MEDI0639 selectively binds to DLL4 and blocks its ability to bind to and activate signaling through the Notch receptors.
|
|
실험적: MEDI0639 Cohort 3
Participants received MEDI0639 dose level 3 as a 60-minute IV infusion on Day 1 of each 21-day cycle.
|
MEDI0639 is an immunoglobulin G1 lambda (IgG1λ) monoclonal antibody.
MEDI0639 selectively binds to DLL4 and blocks its ability to bind to and activate signaling through the Notch receptors.
|
|
실험적: MEDI0639 Cohort 4
Participants received MEDI0639 dose level 4 as a 60-minute IV infusion on Day 1 of each 21-day cycle.
|
MEDI0639 is an immunoglobulin G1 lambda (IgG1λ) monoclonal antibody.
MEDI0639 selectively binds to DLL4 and blocks its ability to bind to and activate signaling through the Notch receptors.
|
|
실험적: MEDI0639 Cohort 5
Participants received MEDI0639 dose level 5 as a 60-minute IV infusion on Day 1 of each 21-day cycle.
|
MEDI0639 is an immunoglobulin G1 lambda (IgG1λ) monoclonal antibody.
MEDI0639 selectively binds to DLL4 and blocks its ability to bind to and activate signaling through the Notch receptors.
|
|
실험적: MEDI0639 Cohort 6
Participants received MEDI0639 dose level 6 as a 60-minute IV infusion on Day 1 of each 21 day cycle.
|
MEDI0639 is an immunoglobulin G1 lambda (IgG1λ) monoclonal antibody.
MEDI0639 selectively binds to DLL4 and blocks its ability to bind to and activate signaling through the Notch receptors.
|
연구는 무엇을 측정합니까?
주요 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
|
Maximum Tolerated Dose (MTD) of MEDI0639
기간: From the first dose of MEDI0639 to 21 days after the first dose
|
The MTD evaluation was based on the dose-limiting toxicity (DLT) evaluable population.
DLT is defined as any Grade 3 or higher treatment-related toxicity that occurred during the DLT evaluation period (defined as the time from the first dose of MEDI0639 to 21 days after the first dose), except for National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) Grade 3 hypertension that could be controlled within 96 hours; Grade 3 symptomatic hypertension of greater than (>) 180 millimetre of mercury (mm Hg) systolic or >120 mm Hg diastolic or asymptomatic hypertension of >200 mm Hg systolic or >120 mm Hg diastolic was considered a DLT.
|
From the first dose of MEDI0639 to 21 days after the first dose
|
|
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
기간: From the first dose of MEDI0639 until 90 days after the last dose of MEDI0639. Maximum time frame across participants was 11 months.
|
An adverse event (AE) is any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a study drug, whether or not considered related to the study drug.
Treatment-emergent AEs (TEAEs) were events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug, for the period extending to 90 days after the last dose of study drug.
The AEs were summarized using Medical Dictionary for Regulatory Activities (MedDRA) version 18.1.
|
From the first dose of MEDI0639 until 90 days after the last dose of MEDI0639. Maximum time frame across participants was 11 months.
|
|
Number of Participants With Treatment-emergent Serious Adverse Events (TESAEs)
기간: From the first dose of MEDI0639 until the end of participation in the study. Maximum time frame across participants was 4 years.
|
A serious AE (SAE) is any AE that results in death (refers to an event, which risk of death at the time of the event; it does not refer to an event that may have led to death), is immediately life threatening, require (or prolong) inpatient hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly or birth defect, or is an important medical event that may jeopardize the participant or may require medical intervention to prevent one of the outcomes listed above.
Treatment-emergent SAEs defined as SAEs present at baseline that worsened in intensity after administration of study drug or SAEs absent at baseline that emerged after administration of study drug.
The SAEs were summarized using MedDRA version 18.1.
|
From the first dose of MEDI0639 until the end of participation in the study. Maximum time frame across participants was 4 years.
|
|
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Laboratory Parameters
기간: From the first dose of MEDI0639 until 90 days after last dose of MEDI0639. Maximum time frame across participants was 11 months.
|
Laboratory evaluations of blood and urine samples were performed, including hematology (white blood cell [WBC] count with differential, red blood cell [RBC] count, hematocrit, hemoglobin, platelet count, mean corpuscular volume [MCV], and mean corpuscular hemoglobin concentration [MCHC]); serum chemistry (calcium, chloride, magnesium, potassium, sodium, bicarbonate, aspartate transaminase [AST], alanine transaminase [ALT], alkaline phosphatase, total bilirubin, liver function test, gamma glutamyl transferase [GGT], lactate dehydrogenase, uric acid, creatinine, blood urea nitrogen [BUN], glucose, albumin, total protein, triglycerides, cholesterol, and troponin); and routine urinalysis.
The TEAEs related to laboratory evaluations in participants were reported.
|
From the first dose of MEDI0639 until 90 days after last dose of MEDI0639. Maximum time frame across participants was 11 months.
|
|
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Signs and Physical Examination
기간: From the first dose of MEDI0639 until 90 days after last dose of MEDI0639. Maximum time frame across participants was 11 months.
|
Vital signs (temperature, blood pressure, pulse rate, and respiratory rate) were performed at baseline and throughout the study.
The TEAEs related to vital signs in participants were reported.
|
From the first dose of MEDI0639 until 90 days after last dose of MEDI0639. Maximum time frame across participants was 11 months.
|
|
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Electrocardiogram (ECG) Evaluations
기간: From the first dose of MEDI0639 until 90 days after last dose of MEDI0639. Maximum time frame across participants was 11 months.
|
ECG parameters included QT interval and corrected QT (QTc) interval.
Electrocardiogram (ECG) parameters were assessed at baseline as well as throughout the study.
All 12-lead ECGs performed during the study were obtained in triplicate.
The TEAEs related to ECG evaluations in participants were reported.
|
From the first dose of MEDI0639 until 90 days after last dose of MEDI0639. Maximum time frame across participants was 11 months.
|
|
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Echocardiogram Evaluations
기간: From the first dose of MEDI0639 until 90 days after last dose of MEDI0639. Maximum time frame across participants was 11 months.
|
Echocardiogram parameters included left ventricular ejection fraction (LVEF) and pulmonary arterial pressure (PAP).
The TEAEs related to echocardiogram evaluations in participants were reported.
|
From the first dose of MEDI0639 until 90 days after last dose of MEDI0639. Maximum time frame across participants was 11 months.
|
2차 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
|
Area Under the Concentration-Time Curve From Time 0 to Infinity (AUCinf) After Cycle 1 Treatment Administration of MEDI0639
기간: Days 1 (prior to start of infusion and 30 mins, 2, and 6 hours post end of infusion), 2, 5 , 8, and 15 of Cycle 1
|
The pharmacokinetics (PK) parameter was estimated using the noncompartmental analysis methods, based on the individual serum concentration-time data.
The concentration-time curve is the result of blood sampling at specified time points and its measured concentration of MEDI0639.
|
Days 1 (prior to start of infusion and 30 mins, 2, and 6 hours post end of infusion), 2, 5 , 8, and 15 of Cycle 1
|
|
Maximum Observed Concentration (Cmax) After Cycle 1 Treatment Administration of MEDI0639
기간: Days 1 (prior to start of infusion and 30 mins, 2, and 6 hours post end of infusion), 2, 5 , 8, and 15 of Cycle 1
|
The pharmacokinetics (PK) parameter was estimated using the noncompartmental analysis methods, based on the individual serum concentration-time data.
The concentration-time curve is the result of blood sampling at specified time points and its measured concentration of MEDI0639.
|
Days 1 (prior to start of infusion and 30 mins, 2, and 6 hours post end of infusion), 2, 5 , 8, and 15 of Cycle 1
|
|
Clearance (CL) After Cycle 1 Treatment Administration of MEDI0639
기간: Days 1 (prior to start of infusion and 30 mins, 2, and 6 hours post end of infusion), 2, 5 , 8, and 15 of Cycle 1
|
The pharmacokinetics (PK) parameter was estimated using the noncompartmental analysis methods, based on the individual serum concentration-time data.
The concentration-time curve is the result of blood sampling at specified time points and its measured concentration of MEDI0639.
Clearance was estimated as dose divided by the area under serum concentration-time curve from time zero to infinity.
|
Days 1 (prior to start of infusion and 30 mins, 2, and 6 hours post end of infusion), 2, 5 , 8, and 15 of Cycle 1
|
|
Half-life (t1/2) After Cycle 1 Treatment Administration of MEDI0639
기간: Days 1 (prior to start of infusion and 30 mins, 2, and 6 hours post end of infusion), 2, 5 , 8, and 15 of Cycle 1
|
The pharmacokinetics (PK) parameter was estimated using the noncompartmental analysis methods, based on the individual serum concentration-time data.
The concentration-time curve is the result of blood sampling at specified time points and its measured concentration of MEDI0639.
|
Days 1 (prior to start of infusion and 30 mins, 2, and 6 hours post end of infusion), 2, 5 , 8, and 15 of Cycle 1
|
|
Number of Participants Positive With Antidrug Antibodies (ADA) for MEDI0639
기간: On Day 1 of Cycles 1, 2, 3, and every other cycle thereafter, end of treatment, 30 days, and 3 and 6 months after the last dose of MEDI0639. Maximum time frame across participants was 14 months.
|
Blood samples were measured for the presence of ADA for MEDI0639 using a validated bridging immunoassay.
Only the number of participants positive for anti-MEDI-575 antibodies at any visit were presented.
|
On Day 1 of Cycles 1, 2, 3, and every other cycle thereafter, end of treatment, 30 days, and 3 and 6 months after the last dose of MEDI0639. Maximum time frame across participants was 14 months.
|
|
Percentage of Participants With Best Overall Response
기간: From study entry through the end of the study. Maximum time frame across participants was 4 years.
|
Percentage (%) of participants who were responders with BOR documented as confirmed CR, PR, stable disease (SD), progressive disease (PD) and non-evaluable (NE).
CR: disappearance of all target lesions.
Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (<)10 mm.
PR: At least a 30 % decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.
PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study).
In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.
|
From study entry through the end of the study. Maximum time frame across participants was 4 years.
|
|
Percentage of Participants With Objective Response
기간: From study entry through the end of the study. Maximum time frame across participants was 4 years.
|
Objective response rate (ORR) defined as the percentage of participants with a BOR of confirmed CR or confirmed PR.
|
From study entry through the end of the study. Maximum time frame across participants was 4 years.
|
|
Percentage of Participants With Disease Control
기간: From study entry through the end of the study. Maximum time frame across participants was 4 years.
|
Disease control rate (DCR) defined as the percentage of participants with a BOR of confirmed CR, confirmed PR or SD.
|
From study entry through the end of the study. Maximum time frame across participants was 4 years.
|
|
Time to Response
기간: From study entry through the end of the study. Maximum time frame across participants was 4 years.
|
Time to response (TTR) defined as the time from the first dose of MEDI0639 until the first documentation of a subsequently confirmed objective response.
Only participants who have achieved objective response (confirmed CR or confirmed PR) was evaluated for TTR.
TTR (months) = (Date of first disease response - Date of the first dose of MEDI0639 + 1) / (365.25/12).
|
From study entry through the end of the study. Maximum time frame across participants was 4 years.
|
|
Duration of Response (DR)
기간: From study entry through the end of the study. Maximum time frame across participants was 4 years.
|
DR defined as time from start of first documented objective response [confirmed Complete Response (CR) or confirmed Partial Response (PR)] to first documented disease progression or death due to any cause, whichever occurs first.
DR calculated as (months) = (Date of PD/death or censoring - Date of first disease response + 1)/ (365.25/12).
|
From study entry through the end of the study. Maximum time frame across participants was 4 years.
|
|
Progression-free Survival (PFS)
기간: From study entry through the end of the study. Maximum time frame across participants was 4 years.
|
Progression-free survival (PFS) is defined as the time from the first dose of MEDI0639 until the first documentation of disease progression or death due to any cause, whichever occurs first.
PFS (months) = (Date of PD/death or censoring - Date of the first dose of MEDI0639 + 1) / (365.25/12).
|
From study entry through the end of the study. Maximum time frame across participants was 4 years.
|
|
Overall Survival
기간: From study entry through the end of the study. Maximum time frame across participants was 4 years.
|
Overall survival defined as the time from the first dose of MEDI0639 until death due to any cause.
OS (months) = (Date of death or censoring - Date of the first dose of MEDI0639 + 1) / (365.25/12).
|
From study entry through the end of the study. Maximum time frame across participants was 4 years.
|
공동 작업자 및 조사자
여기에서 이 연구와 관련된 사람과 조직을 찾을 수 있습니다.
스폰서
연구 기록 날짜
이 날짜는 ClinicalTrials.gov에 대한 연구 기록 및 요약 결과 제출의 진행 상황을 추적합니다. 연구 기록 및 보고된 결과는 공개 웹사이트에 게시되기 전에 특정 품질 관리 기준을 충족하는지 확인하기 위해 국립 의학 도서관(NLM)에서 검토합니다.
연구 주요 날짜
연구 시작
2012년 4월 1일
기본 완료 (실제)
2015년 12월 1일
연구 완료 (실제)
2015년 12월 1일
연구 등록 날짜
최초 제출
2012년 4월 5일
QC 기준을 충족하는 최초 제출
2012년 4월 12일
처음 게시됨 (추정)
2012년 4월 16일
연구 기록 업데이트
마지막 업데이트 게시됨 (실제)
2017년 5월 2일
QC 기준을 충족하는 마지막 업데이트 제출
2017년 3월 21일
마지막으로 확인됨
2017년 3월 1일
추가 정보
이 정보는 변경 없이 clinicaltrials.gov 웹사이트에서 직접 가져온 것입니다. 귀하의 연구 세부 정보를 변경, 제거 또는 업데이트하도록 요청하는 경우 register@clinicaltrials.gov. 문의하십시오. 변경 사항이 clinicaltrials.gov에 구현되는 즉시 저희 웹사이트에도 자동으로 업데이트됩니다. .
고형 종양에 대한 임상 시험
-
AstraZeneca모병Adv Solid Malig - H&N SCC, ATM Pro / Def NSCLC, 위암, 유방암 및 난소암스페인, 미국, 벨기에, 영국, 프랑스, 헝가리, 캐나다, 대한민국, 호주