An Open-Label, Dose-Escalation Study of IMC-20D7S In Participants With Malignant Melanoma
11 marzo 2019 aggiornato da: Eli Lilly and Company
An Open-Label, Dose-Escalation Phase 1/1b Study of the Anti-gp75 Monoclonal Antibody IMC-20D7S In Patients With Malignant Melanoma Who Have Progressed After or During at Least One Treatment With Standard Cytotoxic Treatment or/and Immunotherapy Therapy or For Whom Standard Therapy is Not Indicated
A dose-escalation study designed to determine the safety, maximum tolerated dose (MTD), anti-melanoma activity, antibody blood levels and progression-free survival (PFS) in participants with malignant melanoma receiving IMC-20D7S either every 2 weeks or every 3 weeks.
Panoramica dello studio
Stato
Completato
Condizioni
Tipo di studio
Interventistico
Iscrizione (Effettivo)
27
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
-
-
Massachusetts
-
Boston, Massachusetts, Stati Uniti, 02114
- ImClone Investigational Site
-
-
New York
-
New York, New York, Stati Uniti, 10021
- ImClone Investigational Site
-
-
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:
- Participant has histologically or cytologically confirmed cutaneous, mucosal, or uveal malignant melanoma which has progressed after or during at least 1 treatment with standard cytotoxic treatment or/and immunotherapy [for example (e.g.), treatment with cytokines, monoclonal antibodies, and vaccines] and is not regarded to be a candidate for a potentially curative, higher priority treatment for melanoma
- Participant is ≥18 years of age
- Participant has either measurable disease as defined by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) or evaluable disease
- At least 21 days must have elapsed from major surgery, prior chemotherapy, prior treatment with an investigational agent or device, or prior radiation therapy. Relative to participant's treatment with non-approved biological products (eg, monoclonal antibodies), a minimum of 2 half-lives must have passed for eligibility to be considered
- Participant has resolution of all clinically significant toxic effects of prior cancer therapy to Grade ≤1 according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.02 (NCI-CTCAE v4.02)
- Participant has adequate hematological function, hepatic function, and renal function
Exclusion Criteria:
- Participant has undergone major surgery [e.g., laparotomy, thoracotomy, removal of organ(s)] within 21 days prior to study entry
- Participant has elective or planned surgery to be conducted during the trial
- Participant has documented and/or symptomatic brain or leptomeningeal metastases
- Participant is receiving systemic steroids or other immunosuppressive medications. (Intermittent use of steroid-containing medications e.g., for asthma exacerbation or for skin lesions is permitted)
- Participant has an uncontrolled undercurrent illness
- Participant has a concurrent active malignancy other than adequately treated nonmelanomatous skin cancer or other noninvasive carcinoma or in situ neoplasm
- Participant has a known allergy to any of the treatment components (monoclonal antibodies or other therapeutic proteins such as fresh frozen plasma, human serum albumin, cytokines, or interleukins). In the event that there is suspicion the participant may have allergies, the participant should be excluded
- Participant is pregnant or lactating
- Participant has known human immunodeficiency virus (HIV) or acquired immune deficiency syndrome (AIDS) infection
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
- Assegnazione: Non randomizzato
- Modello interventistico: Assegnazione parallela
- Mascheramento: Nessuno (etichetta aperta)
Armi e interventi
Gruppo di partecipanti / Arm |
Intervento / Trattamento |
|---|---|
|
Sperimentale: IMC-20D7S (1A-4A Cohorts)
Escalating doses up to 30 milligrams per kilogram (mg/kg) administered intravenously (i.v.) every 2 weeks; includes Cohorts 1A, 2A, 3A, and 4A.
|
5 mg/kg i.v. every 2 weeks. Administered every other week on Days 1 and 15 of each treatment cycle. If no dose-limiting toxicity (DLT) in first 3 participants or 1 DLT in 6 participants, then enrollment into Cohort 2A.
Altri nomi:
10 mg/kg i.v. every 2 weeks. Administered every other week on Days 1 and 15 of each treatment cycle. If no DLT in first 3 participants or 1 DLT in 6 participants in Cohort 2A, then enrollment into Cohort 3A.
Altri nomi:
20 mg/kg i.v. every 2 weeks. Administered every other week on Days 1 and 15 of each treatment cycle. If no DLT in first 3 participants or 1 DLT in 6 participants in Cohort 3A, then enrollment into Cohort 4A.
Altri nomi:
30 mg/kg i.v. every 2 weeks. Administered every other week on Days 1 and 15 of each treatment cycle.
Altri nomi:
|
|
Sperimentale: IMC-20D7S (1B-3B Cohorts)
Escalating doses up to 30 mg/kg administered i.v.
every 3 weeks; includes Cohorts 1B, 2B, and 3B.
|
10 mg/kg i.v. every 3 weeks. Administered every 3 weeks on Days 1 and 22 of each treatment cycle. If no dose-limiting toxicity (DLT) in first 3 participants or 1 DLT in 6 participants in Cohort 1B, then enrollment into Cohort 2B.
Altri nomi:
20 mg/kg i.v. every 3 weeks. Administered every 3 weeks on Days 1 and 22 of each treatment cycle. If no DLT in first 3 participants or 1 DLT in 6 participants in Cohort 2B, then enrollment into Cohort 3B.
Altri nomi:
30 mg/kg i.v. every 3 weeks. Administered every 3 weeks on Days 1 and 22 of each treatment cycle.
Altri nomi:
|
Cosa sta misurando lo studio?
Misure di risultato primarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
|---|---|---|
|
Maximum Tolerated Dose (MTD) of IMC-20D7S
Lasso di tempo: Baseline to toxicity [up to end of Cycle 1 (4 or 6-week cycles)]
|
The MTD was defined as the dose preceding the dose level at which 2 participants experienced a dose-limiting toxicity (DLT) during treatment Cycle 1.
A DLT was defined as any Grade 3 or above toxicity that emerged during study treatment and was clearly not attributable to malignant melanoma or co-medication and was possibly, probably, or definitely related to IMC-20D7S in the judgment of the investigator.
No DLT was observed in the study; a provisional MTD was established.
|
Baseline to toxicity [up to end of Cycle 1 (4 or 6-week cycles)]
|
|
Number of Participants With Serious Adverse Events (SAEs), Other Non-Serious Adverse Events (AEs), or Death
Lasso di tempo: Baseline through 30 days post last dose (up to 31 weeks)
|
A summary of SAEs and other non-serious AEs, regardless of causality, is located in the Reported Adverse Event module.
|
Baseline through 30 days post last dose (up to 31 weeks)
|
Misure di risultato secondarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
|---|---|---|
|
IMC-20D7S Pharmacokinetics (PK): Maximum Concentration (Cmax)
Lasso di tempo: Cycles 1 and 3: Prior to, immediately after, and 0.5, 1, 2, 4, 8, 24, 48 (Cycle 3 only), 96, 168, 240, and 336 hours (h) post first infusion. Cycles 2 and 4: Prior to and 1 h post first infusion.
|
A non-validated assay was used to determine individual serum concentrations of IMC-20D7S.
Thus, analyses of PK data were not conducted.
|
Cycles 1 and 3: Prior to, immediately after, and 0.5, 1, 2, 4, 8, 24, 48 (Cycle 3 only), 96, 168, 240, and 336 hours (h) post first infusion. Cycles 2 and 4: Prior to and 1 h post first infusion.
|
|
IMC-20D7S PK: Minimal Concentration (Cmin)
Lasso di tempo: Cycles 1 and 3: Prior to, immediately after, and 0.5, 1, 2, 4, 8, 24, 48 (Cycle 3 only), 96, 168, 240, and 336 h post first infusion. Cycles 2 and 4: Prior to and 1 h post first infusion.
|
A non-validated assay was used to determine individual serum concentrations of IMC-20D7S.
Thus, analyses of PK data were not conducted.
|
Cycles 1 and 3: Prior to, immediately after, and 0.5, 1, 2, 4, 8, 24, 48 (Cycle 3 only), 96, 168, 240, and 336 h post first infusion. Cycles 2 and 4: Prior to and 1 h post first infusion.
|
|
IMC-20D7S PK: Half-life (t½)
Lasso di tempo: Cycles 1 and 3: Prior to, immediately after, and 0.5, 1, 2, 4, 8, 24, 48 (Cycle 3 only), 96, 168, 240, and 336 h post first infusion. Cycles 2 and 4: Prior to and 1 h post first infusion.
|
A non-validated assay was used to determine individual serum concentrations of IMC-20D7S.
Thus, analyses of PK data were not conducted.
|
Cycles 1 and 3: Prior to, immediately after, and 0.5, 1, 2, 4, 8, 24, 48 (Cycle 3 only), 96, 168, 240, and 336 h post first infusion. Cycles 2 and 4: Prior to and 1 h post first infusion.
|
|
IMC-20D7S PK: Clearance (Cl)
Lasso di tempo: Cycles 1 and 3: Prior to, immediately after, and 0.5, 1, 2, 4, 8, 24, 48 (Cycle 3 only), 96, 168, 240, and 336 h post first infusion. Cycles 2 and 4: Prior to and 1 h post first infusion.
|
A non-validated assay was used to determine individual serum concentrations of IMC-20D7S.
Thus, analyses of PK data were not conducted.
|
Cycles 1 and 3: Prior to, immediately after, and 0.5, 1, 2, 4, 8, 24, 48 (Cycle 3 only), 96, 168, 240, and 336 h post first infusion. Cycles 2 and 4: Prior to and 1 h post first infusion.
|
|
IMC-20D7S PK: Area Under the Concentration Versus Time Curve (AUC)
Lasso di tempo: Cycles 1 and 3: Prior to, immediately after, and 0.5, 1, 2, 4, 8, 24, 48 (Cycle 3 only), 96, 168, 240, and 336 h post first infusion. Cycles 2 and 4: Prior to and 1 h post first infusion.
|
A non-validated assay was used to determine individual serum concentrations of IMC-20D7S.
Thus, analyses of PK data were not conducted.
|
Cycles 1 and 3: Prior to, immediately after, and 0.5, 1, 2, 4, 8, 24, 48 (Cycle 3 only), 96, 168, 240, and 336 h post first infusion. Cycles 2 and 4: Prior to and 1 h post first infusion.
|
|
IMC-20D7S PK: Volume of Distribution (Vd) at Steady State
Lasso di tempo: Cycles 1 and 3: Prior to, immediately after, and 0.5, 1, 2, 4, 8, 24, 48 (Cycle 3 only), 96, 168, 240, and 336 h post first infusion. Cycles 2 and 4: Prior to and 1 h post first infusion.
|
A non-validated assay was used to determine individual serum concentrations of IMC-20D7S.
Thus, analyses of PK data were not conducted.
|
Cycles 1 and 3: Prior to, immediately after, and 0.5, 1, 2, 4, 8, 24, 48 (Cycle 3 only), 96, 168, 240, and 336 h post first infusion. Cycles 2 and 4: Prior to and 1 h post first infusion.
|
|
Number of Participants Who Develop Antibodies Against IMC-20D7S (Immunogenicity)
Lasso di tempo: Prior to the first and second infusion in each cycle up to Cycle 7 (4- and 6-week cycles)
|
Planned analyses for immunogenicity were not completed.
A decision was made not to develop a validated immunogenicity assay because of the exploratory nature of the study and the analyses.
|
Prior to the first and second infusion in each cycle up to Cycle 7 (4- and 6-week cycles)
|
|
Progression-Free Survival (PFS)
Lasso di tempo: First dose to disease progression or death (up to 27 weeks)
|
PFS was determined for participants who went beyond their first disease assessment and completed at least 1 treatment beyond Week 1 of treatment Cycle 3.
|
First dose to disease progression or death (up to 27 weeks)
|
|
Recommend Doses for Phase 2/3 Studies Based on MTD
Lasso di tempo: Baseline to toxicity [up to end of Cycle 1 (4-or 6-week cycles)]
|
It was decided for administrative reasons to discontinue dosing at the provisional MTD rather than progress to Phase 1b.
|
Baseline to toxicity [up to end of Cycle 1 (4-or 6-week cycles)]
|
Collaboratori e investigatori
Qui è dove troverai le persone e le organizzazioni coinvolte in questo studio.
Sponsor
Investigatori
- Direttore dello studio: E-mail: ClinicalTrials@ ImClone.com, 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 giugno 2010
Completamento primario (Effettivo)
1 agosto 2012
Completamento dello studio (Effettivo)
1 agosto 2012
Date di iscrizione allo studio
Primo inviato
2 giugno 2010
Primo inviato che soddisfa i criteri di controllo qualità
3 giugno 2010
Primo Inserito (Stima)
4 giugno 2010
Aggiornamenti dei record di studio
Ultimo aggiornamento pubblicato (Effettivo)
17 giugno 2019
Ultimo aggiornamento inviato che soddisfa i criteri QC
11 marzo 2019
Ultimo verificato
1 marzo 2019
Maggiori informazioni
Termini relativi a questo studio
Parole chiave
Termini MeSH pertinenti aggiuntivi
Altri numeri di identificazione dello studio
- 13945
- CP22-0901 (Altro identificatore: ImClone, LLC)
- I4Z-IE-JDEA (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 .