- ICH GCP
- US Clinical Trials Registry
- Klinisk forsøg NCT01957280
Study to Assess Pharmacokinetics, Immunogenicity and Safety/Tolerability of Patritumab (U3-1287)
13. maj 2014 opdateret af: Daiichi Sankyo, Inc.
Phase 1, Open-label Study Assessing the Pharmacokinetics, Immunogenicity and Safety/Tolerability of Process 2 Patritumab in Patients With Advanced, Refractory Solid Tumors
The purpose of this study is to assess the PK, safety, and tolerability of patritumab produced by a new manufacturing process (denoted as "Process 2 patritumab").
The data from this study will allow Process 2 patritumab to be compared to Process 1 patritumab to allow for any dose adjustments, if needed, and to bridge data from studies previously conducted with Process 1 patritumab to studies to be conducted with Process 2 patritumab.
The hypothesis for this study is that the pharmacokinetics of Process 2 patritumab will be comparable to those of Process 1 patritumab.
Studieoversigt
Detaljeret beskrivelse
Process 2 patritumab will be administered intravenously as a single, loading dose of 18 mg/kg over approximately 60 minutes at Cycle 1 Day 1 followed by 9 mg/kg administered every 21 days as a maintenance dose starting at Cycle 2 Day 1.
This study will be conducted in 2 phases: a main study and an extension phase.
The PK profile of Process 2 patritumab will be compared to historical data for Process 1 patritumab.
Specifically, the PK parameters (AUC0-21d and Cmax as primary endpoints) for Process 2 patritumab 18 mg/kg (loading dose) will be compared to the PK parameters of Process 1 patritumab 18 mg/kg.
Process 2 patritumab serum concentrations will be compared to Process 1 patritumab serum concentrations collected in the Phase 1 and Phase 2 studies by population PK methods and will be reported separately.
Undersøgelsestype
Interventionel
Tilmelding (Faktiske)
17
Fase
- Fase 1
Kontakter og lokationer
Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.
Studiesteder
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Florida
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Tampa, Florida, Forenede Stater, 33612
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Oklahoma
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Oklahoma City, Oklahoma, Forenede Stater, 73104
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Texas
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San Antonio, Texas, Forenede Stater, 78229
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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 og ældre (Voksen, Ældre voksen)
Tager imod sunde frivillige
Ingen
Køn, der er berettiget til at studere
Alle
Beskrivelse
Inclusion Criteria:
- Must have a pathologically documented advanced solid tumor that is refractory to standard treatment, for which no standard therapy is available, or for which the subject refuses standard therapy.
- Must have a tumor type that is known to express HER3. These tumors include breast, lung, prostate, ovarian, cervical, endometrial, gastric, pancreatic, bladder, head and neck, liver, colon, and esophageal cancer. Other tumors will be considered based on emerging HER3 expression data.
- Must be competent and able to comprehend, sign, and date an IRB-approved ICF (including HIPAA authorization, if applicable) before performance of any study-specific procedures or tests.
- Must have an ECOG performance status of ≤ 2
Women must be one of the following:
- Postmenopausal (having had no menstrual period for a minimum of 12 months) or surgically sterile, or
- If of childbearing potential, must have been willing to use maximally effective birth control during the period of therapy and use contraception for 6 months following the last investigational drug infusion and must have had a negative urine or serum pregnancy test upon entry into the study.
- Men must be surgically sterile or willing to use a double-barrier contraception method upon enrollment, during the course of the study, and for 6 months following the last investigational drug infusion.
Have hematological function, as follows:6. Men
- Absolute neutrophil count of ≥ 1.5 × 109/L
- Platelet count ≥ 100 × 109/L
- Hemoglobin ≥ 9 g/dL
Have renal function, as follows:
- Calculated creatinine clearance rate (CrCl) ≥ 60 mL/minute using the modified Cockcroft-Gault equation or serum creatinine ≤ 1.5 × ULN.
Have hepatic function, as follows:
- AST ≤ 2.5 × ULN (if liver metastases are present, < 5 × ULN)
- ALT ≤ 2.5 × ULN (if liver metastases are present, < 5 × ULN)
- Alkaline phosphatase ≤ 2.5 × ULN (if bone or liver metastases are present, < 5 × ULN)
- Bilirubin ≤ 1.5 × ULN
- Prothrombin time (PT) or partial thromboplastin time (PTT) ≤ 1.5 × ULN
Exclusion Criteria:
- Have a history of lymphoma, leukemia, or other hematopoietic malignancy.
- Have Have autologous or allogeneic stem cell transplant.
- Have any comorbid medical condition that would increase the risk of toxicity in the opinion of the investigator or sponsor.
- Have untreated or symptomatic brain metastasis.
- Have unresolved toxicities from prior anticancer therapy, defined as having not resolved to NCI CTCAE Version 4.0 Grade 0 or 1, or to levels dictated in the inclusion/exclusion criteria with the exception of alopecia. Subjects with irreversible Grade 2 toxicity may be eligible as per discretion of the investigator and sponsor (e.g., Grade 2 chemotherapy-induced neuropathy).
- Have uncontrolled hypertension (diastolic blood pressure > 100 mmHg or systolic blood pressure > 140 mmHg). It is permissible for the subject to receive treatment with antihypertensive medication to maintain blood pressure within the required parameters.
- Have clinically significant ECG changes that obscure the ability to assess the RR, PR, QT, QT interval corrected for heart rate (QTc), and QRS interval. Subjects with left bundle branch block, atrial fibrillation and use of cardiac pacemaker specifically will be excluded.
- Have ascites or pleural effusion requiring chronic medical intervention.
- Have a history of bleeding diathesis.
- Have had a myocardial infarction within 1 year before enrollment, symptomatic CHF (New York Heart Association > Class II;), unstable angina, or unstable cardiac arrhythmia requiring medication.
- Use of amiodarone within 6 months prior to enrollment.
- Concurrent use of antiarrhythmic medications with the exception of beta blockers for treatment of hypertension.
- Subjects who are receiving drugs that may affect QTc (e.g., quinidine or moxifloxacin).
- QTc interval > 450 msec on the average of the triplicate readings by Friderica's formula on 2 successive screening measurements (second measurement is required if first measurement is > 450 msec).
- Have a LVEF < 50%.
- Have anthracycline exposure greater than 360 mg/m2.
- Have a history of chronic hepatitis or known active infection with hepatitis B virus or hepatitis C virus.
- Personal or family history of long-QT syndrome.
- Have known infection with or a history of testing positive for human immunodeficiency virus (HIV).
- Had treatment with anticancer therapy (6 weeks for nitrosoureas and mitomycin C chemotherapies and 2 weeks for small molecule tyrosine kinase inhibitors), antibody therapy, retinoid therapy, or hormonal therapy within 4 weeks before study Day 1. Prior and concurrent use of hormone replacement therapy or the use of gonadotropin releasing hormone modulators for prostate cancer is permitted.
- Had therapeutic or palliative radiation therapy within 4 weeks before enrollment (in addition, he/she must have had resolution of any significant AEs from radiation therapy at least 2 weeks before enrollment).
- Have concurrent or previous (within 1 week of study Day 1) anticoagulation therapy, except low-dose warfarin (≤ 2 mg/day) or low-dose, low-molecular weight heparin for prophylaxis against central venous catheter thrombosis or deep vein thrombosis.
- Have participated in clinical drug trials within 4 weeks before enrollment.
- Have had major surgery within 4 weeks before enrollment.
- Is currently participating in other investigational procedures.
- Has any disorder that compromised the ability of the subject to give written informed consent and/or comply with study procedures.
- Has known sensitivity to any of the products to be administered during dosing or known allergy to the excipients or investigational drugs.
- Has active infection within 2 weeks before enrollment unless there was a discussion with the sponsor and an agreement was reached that the recent infection would not affect the subject's participation in the study.
- Has previously received an anti-HER3 targeted antibody, including patritumab.
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 |
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Eksperimentel: Process 2 patritumab
Process 2 patritumab 18 mg/kg (loading dose) on Day 1 of Cycle 1 followed by Process 2 patritumab 9 mg/kg (maintenance dose) once every 21 days starting on Day 1 of Cycle 2 through Cycle 5.
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Andre navne:
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Hvad måler undersøgelsen?
Primære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
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AUC (0-21 day) of Patritumab
Tidsramme: 5 Cycles, each of which lasts 21 Days
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AUC (0-21 day) of patritumab obtained after a single infusion of Process 2 patritumab 18 mg/kg (loading dose)
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5 Cycles, each of which lasts 21 Days
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Cmax of Patritumab
Tidsramme: 5 Cycles, each of which lasts 21 Days
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Cmax of patritumab obtained after a single infusion of Process 2 patritumab 18 mg/kg (loading dose)
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5 Cycles, each of which lasts 21 Days
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Sekundære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
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volume of distribution [Vz]
Tidsramme: 5 Cycles, each of which lasts 21 Days
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To assess the secondary PK parameters volume of distribution [Vz]
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5 Cycles, each of which lasts 21 Days
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Safety and Tolerability of Process 2 patritumab - (electrocardiograms [ECG)
Tidsramme: 5 Cycles, each of which lasts 21 Days
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To assess the safety and tolerability of Process 2 patritumab (electrocardiograms [ECG)
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5 Cycles, each of which lasts 21 Days
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Antibody Formation
Tidsramme: 5 Cycles, each of which lasts 21 Days
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To characterize the formation of antibodies to patritumab human antihuman antibodies (HAHA) after infusion of Process 2 patritumab
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5 Cycles, each of which lasts 21 Days
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Concentration patritumab at 504 hours
Tidsramme: 5 Cycles, each of which lasts 21 Days
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To assess the secondary PK parameter concentration of patritumab at 504h [C504]
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5 Cycles, each of which lasts 21 Days
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AUC to infinity [AUC0-inf]
Tidsramme: 5 Cycles, each of which lasts 21 Days
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To assess the secondary PK parameters AUC to infinity [AUC0-inf]
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5 Cycles, each of which lasts 21 Days
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time to Cmax (Tmax)
Tidsramme: 5 Cycles, each of which lasts 21 Days
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To assess the secondary PK parameters time to Cmax (Tmax)
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5 Cycles, each of which lasts 21 Days
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concentration at the end of infusion (Ceoi)
Tidsramme: 5 Cycles, each of which lasts 21 Days
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To assess the secondary PK parameters concentration at the end of infusion (Ceoi)
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5 Cycles, each of which lasts 21 Days
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terminal elimination half-life (t 1/2)
Tidsramme: 5 Cycles, each of which lasts 21 Days
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To assess the secondary PK parameters terminal elimination half-life (t 1/2)
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5 Cycles, each of which lasts 21 Days
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clearance (CL)
Tidsramme: 5 Cycles, each of which lasts 21 Days
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To assess the secondary PK parameters clearance (CL)
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5 Cycles, each of which lasts 21 Days
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trough concentration (Ctrough)
Tidsramme: 5 Cycles, each of which lasts 21 Days
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To assess the secondary PK parameters trough concentration (Ctrough)
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5 Cycles, each of which lasts 21 Days
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echocardiograms/multi-gated acquisition [MUGA] scans of Process 2 patritumab
Tidsramme: 5 Cycles, each of which lasts 21 Days
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To assess the safety and tolerability of Process 2 patritumab echocardiograms/multi-gated acquisition [MUGA] scans
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5 Cycles, each of which lasts 21 Days
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adverse events [AEs] of Process 2 patritumab
Tidsramme: 5 Cycles, each of which lasts 21 Days
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To assess the safety and tolerability of Process 2 patritumab adverse events [AEs] of Process 2 patritumab
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5 Cycles, each of which lasts 21 Days
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Samarbejdspartnere og efterforskere
Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.
Sponsor
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
1. juni 2013
Primær færdiggørelse (Faktiske)
1. oktober 2013
Studieafslutning (Faktiske)
1. april 2014
Datoer for studieregistrering
Først indsendt
12. juni 2013
Først indsendt, der opfyldte QC-kriterier
30. september 2013
Først opslået (Skøn)
8. oktober 2013
Opdateringer af undersøgelsesjournaler
Sidste opdatering sendt (Skøn)
14. maj 2014
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
13. maj 2014
Sidst verificeret
1. maj 2014
Mere information
Begreber relateret til denne undersøgelse
Nøgleord
Andre undersøgelses-id-numre
- U31287-A-U105
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 .
Kliniske forsøg med Faste tumorer
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Memorial Sloan Kettering Cancer CenterRekrutteringSolid tumor | Solid tumor, voksen | Solid tumor, uspecificeret, voksenForenede Stater
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Memorial Sloan Kettering Cancer CenterLincoln Medical and Mental Health CenterRekrutteringSolid tumor | Solid tumor, voksen | Solid tumor, uspecificeret, voksenForenede Stater, Puerto Rico
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Memorial Sloan Kettering Cancer CenterLincoln Medical and Mental Health CenterRekrutteringSolid tumor | Solid tumor, voksen | Solid tumor, uspecificeret, voksenForenede Stater, Puerto Rico
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Sorrento Therapeutics, Inc.Trukket tilbageSolid tumor | Recidiverende solid tumor | Refraktær tumor
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BeiGeneRekrutteringSolid tumor | Avanceret solid tumorForenede Stater, New Zealand, Australien, Kina
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Anjali PawarRekrutteringSolid tumor | Solid tumor, barndomForenede Stater
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Impact Therapeutics, Inc.RekrutteringSolid tumor | Avanceret solid tumorKina, Taiwan, Forenede Stater, Australien
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Partner Therapeutics, Inc.Trukket tilbageSolid tumor | Solid tumor, voksenForenede Stater
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Novartis PharmaceuticalsAfsluttetKræft | Solid tumor | Avanceret solid tumorJapan
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Pyxis Oncology, IncRekrutteringSolid tumor | Avanceret solid tumorForenede Stater, Spanien, Belgien
Kliniske forsøg med patritumab
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Daiichi SankyoMerck Sharp & Dohme LLCRekrutteringMelanom | Livmoderhalskræft | Hoved- og halskræft | Mavekræft | Spiserørskræft | Prostatakræft | Blærekræft | Avanceret solid tumor | Endometriecancer | Ovariekarcinom | PancreascarcinomForenede Stater, Taiwan, Japan
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The Netherlands Cancer InstituteDaiichi Sankyo, Inc.Ikke rekrutterer endnuEGFR-genmutation | Ikke-småcellet lungekarcinom | Avanceret ikke-småcellet planocellulær lungekræft
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SCRI Development Innovations, LLCDaiichi Sankyo, Inc.RekrutteringMetastatisk brystkræft | Lokalt avanceret brystkræftForenede Stater
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Daiichi Sankyo, Inc.AfsluttetMetastatisk tyktarmskræftForenede Stater, Spanien, Belgien, Japan, Frankrig, Det Forenede Kongerige, Italien, Polen
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Samsung Medical CenterIkke rekrutterer endnuSolid tumor, voksenKorea, Republikken
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Daiichi Sankyo Co., Ltd.Daiichi Sankyo, Inc.AfsluttetMetastatisk brystkræftForenede Stater, Japan
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Daiichi SankyoAktiv, ikke rekrutterendeEGFR L858R | EGFR Exon 19 sletning | Ikke-skælvevs ikke-småcellet lungekræftKorea, Republikken, Forenede Stater, Holland, Spanien, Det Forenede Kongerige, Japan, Østrig, Belgien, Italien, Frankrig, Taiwan, Tyskland, Australien, Singapore, Kina, Hong Kong, Norge, Canada, Polen, Portugal, Schweiz
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Daiichi SankyoDaiichi Sankyo Co., Ltd.Aktiv, ikke rekrutterendeIkke-småcellet lungekræft metastatisk | Ikke-småcellet lungekræft med mutation i epidermal vækstfaktorreceptorForenede Stater, Spanien, Korea, Republikken, Frankrig, Det Forenede Kongerige, Taiwan, Australien, Japan, Kina, Holland, Italien, Tyskland, Østrig, Belgien, Bulgarien, Singapore
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SOLTI Breast Cancer Research GroupDaiichi Sankyo, Inc.Aktiv, ikke rekrutterende
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Sorlandet Hospital HFRekruttering