A Study of IMC-RON8 in Advanced Solid Tumors
8. října 2018 aktualizováno: Eli Lilly and Company
Phase 1 Study of the Anti-Ron Receptor Monoclonal Antibody IMC-RON8 in Patients With Advanced Solid Tumors Who No Longer Respond to Standard Therapy or for Whom No Standard Therapy is Available
A dose escalation study to determine the maximum tolerated dose of IMC-RON8 in participants with solid tumors.
Participants can either be dosed once a week, or once every other week.
Přehled studie
Postavení
Dokončeno
Podmínky
Typ studie
Intervenční
Zápis (Aktuální)
39
Fáze
- Fáze 1
Kontakty a umístění
Tato část poskytuje kontaktní údaje pro ty, kteří studii provádějí, a informace o tom, kde se tato studie provádí.
Studijní místa
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Indiana
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Indianapolis, Indiana, Spojené státy, 46202
- For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician
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Michigan
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Detroit, Michigan, Spojené státy, 48201
- For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician
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New York
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New York, New York, Spojené státy, 10065
- For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician
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Kritéria účasti
Výzkumníci hledají lidi, kteří odpovídají určitému popisu, kterému se říká kritéria způsobilosti. Některé příklady těchto kritérií jsou celkový zdravotní stav osoby nebo předchozí léčba.
Kritéria způsobilosti
Věk způsobilý ke studiu
18 let a starší (Dospělý, Starší dospělý)
Přijímá zdravé dobrovolníky
Ne
Pohlaví způsobilá ke studiu
Všechno
Popis
Inclusion Criteria:
- The participant has histologically-confirmed advanced primary or recurrent solid tumors that have not responded to standard therapy or for which no standard therapy is available
- The participant has measurable or non-measurable disease
- The participant has not received major surgery, prior chemotherapy, prior treatment with an investigational agent or device, or prior radiation therapy within 28 days prior to the first dose of study therapy
- The participant has an Eastern Cooperative Oncology Group Performance Status (ECOG PS) score of 0-2
- The participant has adequate hematologic function
- The participant has adequate renal function as defined by serum creatinine ≤1.5 times the institutional upper limit of normal (ULN)
- The participant has a life expectancy >3 months
Exclusion Criteria:
- The participant has received chemotherapy or therapeutic radiation therapy within 28 days prior to the first dose of study therapy
- The participant has ongoing toxicities of >Grade 1 associated with any prior treatment
- The participant has a known sensitivity to monoclonal antibodies or other therapeutic agents, or to agents of similar biologic composition as IMC-RON8
- The participant has received treatment with any monoclonal antibodies within 6 weeks prior to first dose of study therapy
- The participant has received treatment with agents specifically targeting the RON ligand or receptor within 6 weeks prior to first dose of study therapy
- The participant has undergone a major surgical procedure, open biopsy, or experienced a significant traumatic injury within 28 days prior to the first dose of study therapy
- The participant has an ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, serious cardiac arrhythmia (well controlled atrial fibrillation is permitted), psychiatric illness/social situations, active bleeding, or any other serious uncontrolled medical disorders in the opinion of the investigator
- The participant has known or suspected brain or leptomeningeal metastases (participants with a history of brain metastases must have received definitive surgery or radiotherapy, be clinically stable, and may not be taking steroids; participants receiving anticonvulsants are eligible)
- The participant has a serious or nonhealing active wound, ulcer, or bone fracture
- The participant is currently using or has received a thrombolytic agent within 28 days prior to first dose of study therapy
- The participant is receiving full-dose warfarin (participants receiving low-dose warfarin to maintain the patency of permanent, indwelling intravenous catheters are eligible if the international normalized ratio is <1.5)
- The participant is receiving intravenous heparin
Studijní plán
Tato část poskytuje podrobnosti o studijním plánu, včetně toho, jak je studie navržena a co studie měří.
Jak je studie koncipována?
Detaily designu
- Primární účel: Léčba
- Intervenční model: Sekvenční přiřazení
- Maskování: Žádné (otevřený štítek)
Zbraně a zásahy
Skupina účastníků / Arm |
Intervence / Léčba |
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Experimentální: IMC-RON8
A monoclonal antibody to human macrophage-stimulating 1-receptor-8 (RON8).
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5 milligrams per kilogram (mg/kg) intravenously (IV) Once a week for each 4-week treatment cycle, for a total of four doses per cycle. The initial 4-week treatment cycle will be followed by a 2-week observation period. Cohort 1
Ostatní jména:
10 mg/kg IV Once a week for each 4-week treatment cycle, for a total of four doses per cycle. The initial 4-week treatment cycle will be followed by a 2-week observation period. Cohort 2
Ostatní jména:
15 mg/kg IV Once a week for each 4-week treatment cycle, for a total of four doses per cycle. The initial 4-week treatment cycle will be followed by a 2-week observation period. Cohort 3
Ostatní jména:
15 mg/kg IV Once every 2 weeks for each 4-week treatment cycle, for a total of two doses per cycle. Cohort 4
Ostatní jména:
20 mg/kg IV Once every 2 weeks for each 4-week treatment cycle, for a total of two doses per cycle. Cohort 5
Ostatní jména:
25 or 30 mg/kg IV Once every 2 weeks for each 4-week treatment cycle, for a total of two doses per cycle. Cohort 6
Ostatní jména:
30, 35, or 40 mg/kg IV Once every 2 weeks for each 4-week treatment cycle, for a total of two doses per cycle. Cohort 7
Ostatní jména:
20 or 25 mg/kg IV Once every week for each 4-week treatment cycle, for a total of four doses per cycle. Cohort 8
Ostatní jména:
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Co je měření studie?
Primární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
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Maximum Tolerated Dose (MTD) of IMC-RON8
Časové okno: Baseline through end of study treatment (up to 48 weeks)
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The MTD was the previous dose level to that in which 2 of 6 participants experienced dose-limiting toxicities (DLTs).
DLTs were defined as any of the following events: Grade 4 neutropenia lasting >7 days; any Grade 3 or 4 neutropenia complicated by fever ≥38.5 degrees Celsius or infection, Grade 4 thrombocytopenia, or Grade 3 thrombocytopenia complicated by hemorrhage; Grade 3 hepatic toxicity; or any Grade 3 or 4 nonhematologic toxicity (excluding alopecia, fatigue, anorexia, nausea, and vomiting that is controlled with antiemetics).
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Baseline through end of study treatment (up to 48 weeks)
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Sekundární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
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Pharmacokinetics (PK): Maximum Concentration (Cmax) of IMC-RON8
Časové okno: First and fourth or fifth infusion: Predose, immediately postdose through 168 or 336 hours postdose
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The Cmax of IMC-RON8 following the first and multiple IV infusions (the fourth infusion for the qw treatment regimen and the fifth infusion for the q2w treatment regimen) is reported.
PK samples were collected per protocol and individual sampling times varied depending on the treatment arm and infusion (first or multiple).
The geometric mean and geometric coefficient of variation (%CV) were calculated for treatment arms that had ≥3 participants who had evaluable PK samples for Cmax.
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First and fourth or fifth infusion: Predose, immediately postdose through 168 or 336 hours postdose
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PK: Area Under the Curve (AUC) of IMC-RON8
Časové okno: First and fourth or fifth infusion: Predose, immediately postdose through 168 or 336 hours postdose
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The AUC from time 0 to the last quantifiable concentration [AUC(0-tlast)] of IMC-RON8 following the first IV infusion is reported along with the AUC for 1 dosing interval (AUC tau).
Tau = fourth infusion through 168 hours post infusion for the qw regimen and the fifth infusion through 336 hours post infusion for the q2w regimen.
PK samples were collected per protocol and individual sampling times varied depending on the treatment arm and infusion (first or multiple).
The geometric mean and geometric coefficient of variation (%CV) were calculated for treatment arms that had ≥3 participants who had evaluable PK samples for AUC(0-tlast) or AUC tau.
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First and fourth or fifth infusion: Predose, immediately postdose through 168 or 336 hours postdose
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Immunogenicity of IMC-RON8
Časové okno: Prior to first infusion through study completion (up to 52 weeks)
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An immunogenicity assay for IMC-RON8 was not developed due to the decision to not further develop IMC-RON8 based on preliminary results of this study.
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Prior to first infusion through study completion (up to 52 weeks)
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Pharmacodynamics: H-Score of Macrophage-Stimulating 1-Receptor-8 (RON8)
Časové okno: Prior to first infusion through 1 hour post last infusion (end of study treatment, up to 48 weeks)
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The expression of RON8 was measured in cell membrane/cytoplasm by immunohistochemistry (IHC) methods that incorporated both intensity and distribution of staining.
The H-Score was calculated by summing the percentage of cell staining at each intensity multiplied by the weighted intensity of staining: 0 (no staining), 1+ (weak staining), 2+ (medium staining), 3+ (strongest staining).
H-Scores could range from a minimum score of 0 to a maximum score of 300; the maximum score indicated the strongest expression.
Pharmacodynamic samples were collected per protocol and individual sampling times varied depending on the treatment group.
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Prior to first infusion through 1 hour post last infusion (end of study treatment, up to 48 weeks)
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Best Overall Tumor Response (Antitumor Activity of IMC-RON8 in the Treatment of Solid Tumors)
Časové okno: Baseline to measured PD (up to 48 weeks)
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Response was defined using Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST, v 1.1) criteria.
CR was the disappearance of all target and nontarget lesions; and any pathological lymph node (whether target or nontarget) must have had a reduction in short axis to <10 millimeters (mm) and normalization of tumor marker level of nontarget lesions.
The disappearance of any intratumoral arterial enhancement in all target lesions was also required.
PR was having at least a 30% decrease in sum of longest diameter of target lesions.
PD was having at least 20% increase in sum of longest diameter of target lesions and minimum 5 mm increase above nadir and the unequivocal progression of existing nontarget lesions.
SD was small changes that did not meet the above criteria.
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Baseline to measured PD (up to 48 weeks)
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Další výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
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Number of Participants Who Died
Časové okno: Baseline through study completion (up to 52 weeks)
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The number of participants who died is reported by cause of death.
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Baseline through study completion (up to 52 weeks)
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Spolupracovníci a vyšetřovatelé
Zde najdete lidi a organizace zapojené do této studie.
Sponzor
Termíny studijních záznamů
Tato data sledují průběh záznamů studie a předkládání souhrnných výsledků na ClinicalTrials.gov. Záznamy ze studií a hlášené výsledky jsou před zveřejněním na veřejné webové stránce přezkoumány Národní lékařskou knihovnou (NLM), aby se ujistily, že splňují specifické standardy kontroly kvality.
Hlavní termíny studia
Začátek studia
1. května 2010
Primární dokončení (Aktuální)
1. listopadu 2013
Dokončení studie (Aktuální)
1. listopadu 2013
Termíny zápisu do studia
První předloženo
6. května 2010
První předloženo, které splnilo kritéria kontroly kvality
6. května 2010
První zveřejněno (Odhad)
7. května 2010
Aktualizace studijních záznamů
Poslední zveřejněná aktualizace (Aktuální)
15. února 2019
Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality
8. října 2018
Naposledy ověřeno
1. října 2018
Více informací
Termíny související s touto studií
Klíčová slova
Další identifikační čísla studie
- 13958
- CP21-0901 (Jiný identifikátor: ImClone Systems)
- I5D-IE-JRCA (Jiný identifikátor: Eli Lilly and Company)
Tyto informace byly beze změn načteny přímo z webu clinicaltrials.gov. Máte-li jakékoli požadavky na změnu, odstranění nebo aktualizaci podrobností studie, kontaktujte prosím register@clinicaltrials.gov. Jakmile bude změna implementována na clinicaltrials.gov, bude automaticky aktualizována i na našem webu .