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A Dose-escalation Study to Evaluate the Safety, Tolerability, and Antitumor Activity of MEDI-573 in Subjects With Advanced Solid Tumors

31. oktober 2018 opdateret af: 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.

Studieoversigt

Status

Afsluttet

Betingelser

Intervention / Behandling

Undersøgelsestype

Interventionel

Tilmelding (Faktiske)

43

Fase

  • Fase 1

Kontakter og lokationer

Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.

Studiesteder

  • Forenede Stater
    • Arizona
      • Scottsdale, Arizona, Forenede Stater, 85259
        • Research Site
    • Florida
      • Jacksonville, Florida, Forenede Stater, 32224
        • Research Site
    • Massachusetts
      • Boston, Massachusetts, Forenede Stater, 02115
        • Research Site
    • Michigan
      • Detroit, Michigan, Forenede Stater, 48201
        • Research Site
    • Minnesota
      • Rochester, Minnesota, Forenede Stater, 55905
        • Research Site
    • Pennsylvania
      • Philadelphia, Pennsylvania, Forenede Stater, 19111
        • Research Site

Deltagelseskriterier

Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.

Berettigelseskriterier

Aldre berettiget til at studere

18 år til 99 år (Voksen, Ældre voksen)

Tager imod sunde frivillige

Ingen

Køn, der er berettiget til at studere

Alle

Beskrivelse

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.

Studieplan

Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.

Hvordan er undersøgelsen tilrettelagt?

Design detaljer

  • Primært formål: Behandling
  • Tildeling: N/A
  • Interventionel model: Enkelt gruppeopgave
  • Maskning: Ingen (Åben etiket)

Våben og indgreb

Deltagergruppe / Arm
Intervention / Behandling
Eksperimentel: 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.
Medicin: MEDI-573
Administered at a dose determined by the subject's enrollment cohort as an IV infusion as part of a 21 day treatment cycle.
Eksperimentel: 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.
Medicin: MEDI-573
Administered at a dose determined by the subject's enrollment cohort as an IV infusion as part of a 21 day treatment cycle.
Eksperimentel: 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.
Medicin: MEDI-573
Administered at a dose determined by the subject's enrollment cohort as an IV infusion as part of a 21 day treatment cycle.
Eksperimentel: 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.
Medicin: MEDI-573
Administered at a dose determined by the subject's enrollment cohort as an IV infusion as part of a 21 day treatment cycle.
Eksperimentel: 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.
Medicin: MEDI-573
Administered at a dose determined by the subject's enrollment cohort as an IV infusion as part of a 21 day treatment cycle.
Eksperimentel: 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.
Medicin: MEDI-573
Administered at a dose determined by the subject's enrollment cohort as an IV infusion as part of a 21 day treatment cycle.
Eksperimentel: 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.
Medicin: MEDI-573
Administered at a dose determined by the subject's enrollment cohort as an IV infusion as part of a 21 day treatment cycle.
Eksperimentel: 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.
Medicin: MEDI-573
Administered at a dose determined by the subject's enrollment cohort as an IV infusion as part of a 21 day treatment cycle.
Eksperimentel: 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.
Medicin: MEDI-573
Administered at a dose determined by the subject's enrollment cohort as an IV infusion as part of a 21 day treatment cycle.

Hvad måler undersøgelsen?

Primære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (SAEs)
Tidsramme: From the start of study treatment through 30 days after the last dose of MEDI-573, up to 3.5 years
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.
From the start of study treatment through 30 days after the last dose of MEDI-573, up to 3.5 years
Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs
Tidsramme: From the start of study treatment through 30 days after the last dose of MEDI-573, up to 3.5 years
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.
From the start of study treatment through 30 days after the last dose of MEDI-573, up to 3.5 years
Number of Participants With Vital Signs and Physical Findings Abnormalities Reported as TEAEs
Tidsramme: From the start of study treatment through 30 days after the last dose of MEDI-573, up to 3.5 years
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.
From the start of study treatment through 30 days after the last dose of MEDI-573, up to 3.5 years
Maximum Tolerated Dose (MTD) of MEDI-573
Tidsramme: Cycle 1 Day 1 through Cycle 1 Day 21
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.
Cycle 1 Day 1 through Cycle 1 Day 21
Number of Participants With Dose-Limiting Toxicities (DLTs)
Tidsramme: Cycle 1 Day 1 through Cycle 1 Day 21
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.
Cycle 1 Day 1 through Cycle 1 Day 21
Optimal Biologically Effective Dose (OBED) of MEDI-573
Tidsramme: From the start of study treatment through 30 days after the last dose of MEDI-573, up to 3.5 years
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.
From the start of study treatment through 30 days after the last dose of MEDI-573, up to 3.5 years

Sekundære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Maximum Observed Serum Concentration (Cmax) After the First Dose
Tidsramme: 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
The Cmax was the maximum observed serum concentration of MEDI-573.
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
Time to Reach Maximum Observed Concentration (Tmax) After the First Dose
Tidsramme: 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
The tmax was defined as actual sampling time to reach the maximum observed serum concentration of MEDI-573.
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
Trough Serum Concentration (Ctrough) After the First Dose
Tidsramme: 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
The Ctrough was the lowest serum concentration of MEDI-573 within a dosing interval.
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
Dose Normalized Cmax (Cmax/Dose) After the First Dose
Tidsramme: 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
The Cmax/dose was the dose-normalized maximum serum concentration of MEDI-573.
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
Area Under the Serum Concentration-time Curve Over the First Dosing Interval (AUCτ)
Tidsramme: 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
Area under the serum concentration-time curve over the first dosing interval.
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
Dose-normalized Area Under the Serum Concentration Time Curve Over the First Dosing Interval (AUCτ/Dose)
Tidsramme: 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
The AUCtau/dose was a measure of dose-normalized area under the serum concentration-time curve over the first dosing interval.
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
Number of Participants With Positive Anti-Drug Antibodies (ADA) to MEDI-573
Tidsramme: Pre-infusion on Day 1 of each cycle, end of treatment, and 90 days after last dose MEDI-573 (up to 3.5 years)
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.
Pre-infusion on Day 1 of each cycle, end of treatment, and 90 days after last dose MEDI-573 (up to 3.5 years)
Objective Response Rate (ORR)
Tidsramme: From study entry through the end of the study, up to 3.5 years
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.
From study entry through the end of the study, up to 3.5 years
Progression-free Survival (PFS)
Tidsramme: From study entry through the end of the study, up to 3.5 years
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.
From study entry through the end of the study, up to 3.5 years
Time to Progression
Tidsramme: From study entry through the end of the study, up to 3.5 years
Time to disease progression (TTP) was defined as the duration from the start of treatment with MEDI-573 until the documentation of disease progression.
From study entry through the end of the study, up to 3.5 years
Overall Survival
Tidsramme: From study entry through the end of the study, up to 3.5 years
Overall survival (OS) was defined as the time from the start of treatment with MEDI-573 until death.
From study entry through the end of the study, up to 3.5 years
Time to Response (TTR)
Tidsramme: From study entry through the end of the study, up to 3.5 years
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.
From study entry through the end of the study, up to 3.5 years
Duration of Response
Tidsramme: From study entry through the end of the study, up to 3.5 years
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.
From study entry through the end of the study, up to 3.5 years
Suppression Profiles of IGF-I and IGF-II Post-Administration of MEDI-573
Tidsramme: From the start of study treatment through 30 days after the last dose of MEDI-573, up to 3.5 years
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.
From the start of study treatment through 30 days after the last dose of MEDI-573, up to 3.5 years

Samarbejdspartnere og efterforskere

Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.

Sponsor

MedImmune LLC

Efterforskere

  • Studieleder: Susan Perez, MD, MSc, MedImmune LLC

Publikationer og nyttige links

Den person, der er ansvarlig for at indtaste oplysninger om undersøgelsen, leverer frivilligt disse publikationer. Disse kan handle om alt relateret til undersøgelsen.

Hjælpsomme links

Datoer for undersøgelser

Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.

Studer store datoer

Studiestart (Faktiske)

9. marts 2009

Primær færdiggørelse (Faktiske)

11. september 2012

Studieafslutning (Faktiske)

11. september 2012

Datoer for studieregistrering

Først indsendt

23. december 2008

Først indsendt, der opfyldte QC-kriterier

30. december 2008

Først opslået (Skøn)

1. januar 2009

Opdateringer af undersøgelsesjournaler

Sidste opdatering sendt (Faktiske)

4. marts 2019

Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier

31. oktober 2018

Sidst verificeret

1. oktober 2018

Mere information

Begreber relateret til denne undersøgelse

Andre undersøgelses-id-numre

  • MI-CP184

Lægemiddel- og udstyrsoplysninger, undersøgelsesdokumenter

Studerer et amerikansk FDA-reguleret lægemiddelprodukt

Ja

Studerer et amerikansk FDA-reguleret enhedsprodukt

Ingen

Disse oplysninger blev hentet direkte fra webstedet clinicaltrials.gov uden ændringer. Hvis du har nogen anmodninger om at ændre, fjerne eller opdatere dine undersøgelsesoplysninger, bedes du kontakte register@clinicaltrials.gov. Så snart en ændring er implementeret på clinicaltrials.gov, vil denne også blive opdateret automatisk på vores hjemmeside .

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