An Open-Label, Dose-Escalation Study of IMC-20D7S In Participants With Malignant Melanoma
11 mars 2019 mis à jour par: 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.
Aperçu de l'étude
Statut
Complété
Les conditions
Type d'étude
Interventionnel
Inscription (Réel)
27
Phase
- La phase 1
Contacts et emplacements
Cette section fournit les coordonnées de ceux qui mènent l'étude et des informations sur le lieu où cette étude est menée.
Lieux d'étude
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Massachusetts
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Boston, Massachusetts, États-Unis, 02114
- ImClone Investigational Site
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New York
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New York, New York, États-Unis, 10021
- ImClone Investigational Site
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Critères de participation
Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.
Critère d'éligibilité
Âges éligibles pour étudier
18 ans et plus (Adulte, Adulte plus âgé)
Accepte les volontaires sains
Non
Sexes éligibles pour l'étude
Tout
La description
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
Plan d'étude
Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.
Comment l'étude est-elle conçue ?
Détails de conception
- Objectif principal: Traitement
- Répartition: Non randomisé
- Modèle interventionnel: Affectation parallèle
- Masquage: Aucun (étiquette ouverte)
Armes et Interventions
Groupe de participants / Bras |
Intervention / Traitement |
|---|---|
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Expérimental: 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.
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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.
Autres noms:
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.
Autres noms:
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.
Autres noms:
30 mg/kg i.v. every 2 weeks. Administered every other week on Days 1 and 15 of each treatment cycle.
Autres noms:
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Expérimental: IMC-20D7S (1B-3B Cohorts)
Escalating doses up to 30 mg/kg administered i.v.
every 3 weeks; includes Cohorts 1B, 2B, and 3B.
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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.
Autres noms:
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.
Autres noms:
30 mg/kg i.v. every 3 weeks. Administered every 3 weeks on Days 1 and 22 of each treatment cycle.
Autres noms:
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Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
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Maximum Tolerated Dose (MTD) of IMC-20D7S
Délai: Baseline to toxicity [up to end of Cycle 1 (4 or 6-week cycles)]
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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.
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Baseline to toxicity [up to end of Cycle 1 (4 or 6-week cycles)]
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Number of Participants With Serious Adverse Events (SAEs), Other Non-Serious Adverse Events (AEs), or Death
Délai: Baseline through 30 days post last dose (up to 31 weeks)
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A summary of SAEs and other non-serious AEs, regardless of causality, is located in the Reported Adverse Event module.
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Baseline through 30 days post last dose (up to 31 weeks)
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Mesures de résultats secondaires
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
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IMC-20D7S Pharmacokinetics (PK): Maximum Concentration (Cmax)
Délai: 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.
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A non-validated assay was used to determine individual serum concentrations of IMC-20D7S.
Thus, analyses of PK data were not conducted.
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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.
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IMC-20D7S PK: Minimal Concentration (Cmin)
Délai: 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.
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A non-validated assay was used to determine individual serum concentrations of IMC-20D7S.
Thus, analyses of PK data were not conducted.
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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.
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IMC-20D7S PK: Half-life (t½)
Délai: 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.
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A non-validated assay was used to determine individual serum concentrations of IMC-20D7S.
Thus, analyses of PK data were not conducted.
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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.
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IMC-20D7S PK: Clearance (Cl)
Délai: 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.
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IMC-20D7S PK: Area Under the Concentration Versus Time Curve (AUC)
Délai: 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.
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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.
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IMC-20D7S PK: Volume of Distribution (Vd) at Steady State
Délai: 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.
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A non-validated assay was used to determine individual serum concentrations of IMC-20D7S.
Thus, analyses of PK data were not conducted.
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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.
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Number of Participants Who Develop Antibodies Against IMC-20D7S (Immunogenicity)
Délai: Prior to the first and second infusion in each cycle up to Cycle 7 (4- and 6-week cycles)
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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.
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Prior to the first and second infusion in each cycle up to Cycle 7 (4- and 6-week cycles)
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Progression-Free Survival (PFS)
Délai: First dose to disease progression or death (up to 27 weeks)
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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.
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First dose to disease progression or death (up to 27 weeks)
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Recommend Doses for Phase 2/3 Studies Based on MTD
Délai: Baseline to toxicity [up to end of Cycle 1 (4-or 6-week cycles)]
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It was decided for administrative reasons to discontinue dosing at the provisional MTD rather than progress to Phase 1b.
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Baseline to toxicity [up to end of Cycle 1 (4-or 6-week cycles)]
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Collaborateurs et enquêteurs
C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.
Parrainer
Les enquêteurs
- Directeur d'études: E-mail: ClinicalTrials@ ImClone.com, Eli Lilly and Company
Dates d'enregistrement des études
Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.
Dates principales de l'étude
Début de l'étude
1 juin 2010
Achèvement primaire (Réel)
1 août 2012
Achèvement de l'étude (Réel)
1 août 2012
Dates d'inscription aux études
Première soumission
2 juin 2010
Première soumission répondant aux critères de contrôle qualité
3 juin 2010
Première publication (Estimation)
4 juin 2010
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Réel)
17 juin 2019
Dernière mise à jour soumise répondant aux critères de contrôle qualité
11 mars 2019
Dernière vérification
1 mars 2019
Plus d'information
Termes liés à cette étude
Termes MeSH pertinents supplémentaires
Autres numéros d'identification d'étude
- 13945
- CP22-0901 (Autre identifiant: ImClone, LLC)
- I4Z-IE-JDEA (Autre identifiant: Eli Lilly and Company)
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