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A Study of IMC-RON8 in Advanced Solid Tumors

8 ottobre 2018 aggiornato da: 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.

Panoramica dello studio

Stato

Completato

Condizioni

Intervento / Trattamento

Tipo di studio

Interventistico

Iscrizione (Effettivo)

39

Fase

  • Fase 1

Contatti e Sedi

Questa sezione fornisce i recapiti di coloro che conducono lo studio e informazioni su dove viene condotto lo studio.

Luoghi di studio

  • Stati Uniti
    • Indiana
      • Indianapolis, Indiana, Stati Uniti, 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
    • Michigan
      • Detroit, Michigan, Stati Uniti, 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
    • New York
      • New York, New York, Stati Uniti, 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

Criteri di partecipazione

I ricercatori cercano persone che corrispondano a una certa descrizione, chiamata criteri di ammissibilità. Alcuni esempi di questi criteri sono le condizioni generali di salute di una persona o trattamenti precedenti.

Criteri di ammissibilità

Età idonea allo studio

18 anni e precedenti (Adulto, Adulto più anziano)

Accetta volontari sani

No

Sessi ammissibili allo studio

Tutto

Descrizione

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

Piano di studio

Questa sezione fornisce i dettagli del piano di studio, compreso il modo in cui lo studio è progettato e ciò che lo studio sta misurando.

Come è strutturato lo studio?

Dettagli di progettazione

  • Scopo principale: Trattamento
  • Modello interventistico: Assegnazione sequenziale
  • Mascheramento: Nessuno (etichetta aperta)

Armi e interventi

Gruppo di partecipanti / Arm
Intervento / Trattamento
Sperimentale: IMC-RON8
A monoclonal antibody to human macrophage-stimulating 1-receptor-8 (RON8).
Biologico: IMC-RON8

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

Altri nomi:
  • Narnatumab
  • LY3012219
Biologico: IMC-RON8

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

Altri nomi:
  • Narnatumab
  • LY3012219
Biologico: IMC-RON8

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

Altri nomi:
  • Narnatumab
  • LY3012219
Biologico: IMC-RON8

15 mg/kg IV

Once every 2 weeks for each 4-week treatment cycle, for a total of two doses per cycle.

Cohort 4

Altri nomi:
  • Narnatumab
  • LY3012219
Biologico: IMC-RON8

20 mg/kg IV

Once every 2 weeks for each 4-week treatment cycle, for a total of two doses per cycle.

Cohort 5

Altri nomi:
  • Narnatumab
  • LY3012219
Biologico: IMC-RON8

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

Altri nomi:
  • Narnatumab
  • LY3012219
Biologico: IMC-RON8

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

Altri nomi:
  • Narnatumab
  • LY3012219
Biologico: IMC-RON8

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

Altri nomi:
  • Narnatumab
  • LY3012219

Cosa sta misurando lo studio?

Misure di risultato primarie

Misura del risultato
Misura Descrizione
Lasso di tempo
Maximum Tolerated Dose (MTD) of IMC-RON8
Lasso di tempo: Baseline through end of study treatment (up to 48 weeks)
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).
Baseline through end of study treatment (up to 48 weeks)

Misure di risultato secondarie

Misura del risultato
Misura Descrizione
Lasso di tempo
Pharmacokinetics (PK): Maximum Concentration (Cmax) of IMC-RON8
Lasso di tempo: First and fourth or fifth infusion: Predose, immediately postdose through 168 or 336 hours postdose
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.
First and fourth or fifth infusion: Predose, immediately postdose through 168 or 336 hours postdose
PK: Area Under the Curve (AUC) of IMC-RON8
Lasso di tempo: First and fourth or fifth infusion: Predose, immediately postdose through 168 or 336 hours postdose
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.
First and fourth or fifth infusion: Predose, immediately postdose through 168 or 336 hours postdose
Immunogenicity of IMC-RON8
Lasso di tempo: Prior to first infusion through study completion (up to 52 weeks)
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.
Prior to first infusion through study completion (up to 52 weeks)
Pharmacodynamics: H-Score of Macrophage-Stimulating 1-Receptor-8 (RON8)
Lasso di tempo: Prior to first infusion through 1 hour post last infusion (end of study treatment, up to 48 weeks)
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.
Prior to first infusion through 1 hour post last infusion (end of study treatment, up to 48 weeks)
Best Overall Tumor Response (Antitumor Activity of IMC-RON8 in the Treatment of Solid Tumors)
Lasso di tempo: Baseline to measured PD (up to 48 weeks)
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.
Baseline to measured PD (up to 48 weeks)

Altre misure di risultato

Misura del risultato
Misura Descrizione
Lasso di tempo
Number of Participants Who Died
Lasso di tempo: Baseline through study completion (up to 52 weeks)
The number of participants who died is reported by cause of death.
Baseline through study completion (up to 52 weeks)

Collaboratori e investigatori

Qui è dove troverai le persone e le organizzazioni coinvolte in questo studio.

Sponsor

Eli Lilly and Company

Studiare le date dei record

Queste date tengono traccia dell'avanzamento della registrazione dello studio e dell'invio dei risultati di sintesi a ClinicalTrials.gov. I record degli studi e i risultati riportati vengono esaminati dalla National Library of Medicine (NLM) per assicurarsi che soddisfino specifici standard di controllo della qualità prima di essere pubblicati sul sito Web pubblico.

Studia le date principali

Inizio studio

1 maggio 2010

Completamento primario (Effettivo)

1 novembre 2013

Completamento dello studio (Effettivo)

1 novembre 2013

Date di iscrizione allo studio

Primo inviato

6 maggio 2010

Primo inviato che soddisfa i criteri di controllo qualità

6 maggio 2010

Primo Inserito (Stima)

7 maggio 2010

Aggiornamenti dei record di studio

Ultimo aggiornamento pubblicato (Effettivo)

15 febbraio 2019

Ultimo aggiornamento inviato che soddisfa i criteri QC

8 ottobre 2018

Ultimo verificato

1 ottobre 2018

Maggiori informazioni

Termini relativi a questo studio

Parole chiave

Altri numeri di identificazione dello studio

  • 13958
  • CP21-0901 (Altro identificatore: ImClone Systems)
  • I5D-IE-JRCA (Altro identificatore: Eli Lilly and Company)

Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .

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