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A Phase 1 Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of MEDI0639 in Advanced Solid Tumors

2017年3月21日 更新者：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.

調査の概要

状態

完了

条件

介入・治療

詳細な説明

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.

研究の種類

介入

入学 (実際)

58

段階

  • フェーズ 1

連絡先と場所

このセクションには、調査を実施する担当者の連絡先の詳細と、この調査が実施されている場所に関する情報が記載されています。

研究場所

  • アメリカ
    • California
      • Los Angeles、California、アメリカ、90404
        • Research Site
    • Connecticut
      • New Haven、Connecticut、アメリカ、06513
        • Research Site
    • Massachusetts
      • Boston、Massachusetts、アメリカ
        • Research Site
    • Michigan
      • Ann Arbor、Michigan、アメリカ、48103
        • Research Site
    • Minnesota
      • Minneapolis、Minnesota、アメリカ
        • Research Site
    • New York
      • New York、New York、アメリカ、10002
        • Research Site
    • Ohio
      • Cincinnati、Ohio、アメリカ、45201
        • Research Site
      • Cleveland、Ohio、アメリカ、44105
        • Research Site
    • Texas
      • Houston、Texas、アメリカ、77030
        • Research Site
    • Washington
      • Seattle、Washington、アメリカ、98112
        • Research Site
      • Tacoma、Washington、アメリカ、98405
        • Research Site

参加基準

研究者は、適格基準と呼ばれる特定の説明に適合する人を探します。これらの基準のいくつかの例は、人の一般的な健康状態または以前の治療です。

適格基準

就学可能な年齢

18年～99年 (大人、高齢者)

健康ボランティアの受け入れ

いいえ

受講資格のある性別

全て

説明

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

研究計画

このセクションでは、研究がどのように設計され、研究が何を測定しているかなど、研究計画の詳細を提供します。

研究はどのように設計されていますか？

デザインの詳細

  • 主な目的：処理
  • 割り当て：なし
  • 介入モデル：単一グループの割り当て
  • マスキング：なし（オープンラベル）

武器と介入

参加者グループ / アーム
介入・治療
実験的：MEDI0639 Cohort 1
Participants received MEDI0639 dose level 1 as a 60-minute intravenous (IV) infusion on Day 1 of each 21-day cycle.
生物学的：MEDI0639
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.
実験的：MEDI0639 Cohort 2
Participants received MEDI0639 dose level 2 as a 60-minute IV infusion on Day 1 of each 21-day cycle.
生物学的：MEDI0639
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.
実験的：MEDI0639 Cohort 3
Participants received MEDI0639 dose level 3 as a 60-minute IV infusion on Day 1 of each 21-day cycle.
生物学的：MEDI0639
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.
実験的：MEDI0639 Cohort 4
Participants received MEDI0639 dose level 4 as a 60-minute IV infusion on Day 1 of each 21-day cycle.
生物学的：MEDI0639
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.
実験的：MEDI0639 Cohort 5
Participants received MEDI0639 dose level 5 as a 60-minute IV infusion on Day 1 of each 21-day cycle.
生物学的：MEDI0639
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.
実験的：MEDI0639 Cohort 6
Participants received MEDI0639 dose level 6 as a 60-minute IV infusion on Day 1 of each 21 day cycle.
生物学的：MEDI0639
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.

この研究は何を測定していますか？

主要な結果の測定

結果測定
メジャーの説明
時間枠
Maximum Tolerated Dose (MTD) of MEDI0639
時間枠：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)
時間枠：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)
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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.

二次結果の測定

結果測定
メジャーの説明
時間枠
Area Under the Concentration-Time Curve From Time 0 to Infinity (AUCinf) After Cycle 1 Treatment Administration of MEDI0639
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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)
時間枠：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)
時間枠：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
時間枠：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.

協力者と研究者

ここでは、この調査に関係する人々や組織を見つけることができます。

スポンサー

MedImmune LLC

研究記録日

これらの日付は、ClinicalTrials.gov への研究記録と要約結果の提出の進捗状況を追跡します。研究記録と報告された結果は、国立医学図書館 (NLM) によって審査され、公開 Web サイトに掲載される前に、特定の品質管理基準を満たしていることが確認されます。

主要日程の研究

研究開始

2012年4月1日

一次修了 (実際)

2015年12月1日

研究の完了 (実際)

2015年12月1日

試験登録日

最初に提出

2012年4月5日

QC基準を満たした最初の提出物

2012年4月12日

最初の投稿 (見積もり)

2012年4月16日

学習記録の更新

投稿された最後の更新 (実際)

2017年5月2日

QC基準を満たした最後の更新が送信されました

2017年3月21日

最終確認日

2017年3月1日

詳しくは

本研究に関する用語

キーワード

追加の関連 MeSH 用語

その他の研究ID番号

  • CD-ON-MEDI0639-1078

この情報は、Web サイト clinicaltrials.gov から変更なしで直接取得したものです。研究の詳細を変更、削除、または更新するリクエストがある場合は、register@clinicaltrials.gov。 までご連絡ください。 clinicaltrials.gov に変更が加えられるとすぐに、ウェブサイトでも自動的に更新されます。

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