An Open-Label, Dose-Escalation Study of IMC-20D7S In Participants With Malignant Melanoma
11 mars 2019 uppdaterad av: 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.
Studieöversikt
Status
Avslutad
Betingelser
Studietyp
Interventionell
Inskrivning (Faktisk)
27
Fas
- Fas 1
Kontakter och platser
Det här avsnittet innehåller kontaktuppgifter för dem som genomför studien och information om var denna studie genomförs.
Studieorter
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Massachusetts
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Boston, Massachusetts, Förenta staterna, 02114
- ImClone Investigational Site
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New York
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New York, New York, Förenta staterna, 10021
- ImClone Investigational Site
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Deltagandekriterier
Forskare letar efter personer som passar en viss beskrivning, så kallade behörighetskriterier. Några exempel på dessa kriterier är en persons allmänna hälsotillstånd eller tidigare behandlingar.
Urvalskriterier
Åldrar som är berättigade till studier
18 år och äldre (Vuxen, Äldre vuxen)
Tar emot friska volontärer
Nej
Kön som är behöriga för studier
Allt
Beskrivning
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
Studieplan
Det här avsnittet ger detaljer om studieplanen, inklusive hur studien är utformad och vad studien mäter.
Hur är studien utformad?
Designdetaljer
- Primärt syfte: Behandling
- Tilldelning: Icke-randomiserad
- Interventionsmodell: Parallellt uppdrag
- Maskning: Ingen (Open Label)
Vapen och interventioner
Deltagargrupp / Arm |
Intervention / Behandling |
|---|---|
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Experimentell: 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.
Andra namn:
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.
Andra namn:
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.
Andra namn:
30 mg/kg i.v. every 2 weeks. Administered every other week on Days 1 and 15 of each treatment cycle.
Andra namn:
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Experimentell: 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.
Andra namn:
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.
Andra namn:
30 mg/kg i.v. every 3 weeks. Administered every 3 weeks on Days 1 and 22 of each treatment cycle.
Andra namn:
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Vad mäter studien?
Primära resultatmått
Resultatmått |
Åtgärdsbeskrivning |
Tidsram |
|---|---|---|
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Maximum Tolerated Dose (MTD) of IMC-20D7S
Tidsram: 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
Tidsram: 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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Sekundära resultatmått
Resultatmått |
Åtgärdsbeskrivning |
Tidsram |
|---|---|---|
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IMC-20D7S Pharmacokinetics (PK): Maximum Concentration (Cmax)
Tidsram: 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)
Tidsram: 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)
Tidsram: 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)
Tidsram: 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: Area Under the Concentration Versus Time Curve (AUC)
Tidsram: 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: Volume of Distribution (Vd) at Steady State
Tidsram: 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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Number of Participants Who Develop Antibodies Against IMC-20D7S (Immunogenicity)
Tidsram: 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)
Tidsram: 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
Tidsram: 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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Samarbetspartners och utredare
Det är här du hittar personer och organisationer som är involverade i denna studie.
Sponsor
Utredare
- Studierektor: E-mail: ClinicalTrials@ ImClone.com, Eli Lilly and Company
Studieavstämningsdatum
Dessa datum spårar framstegen för inlämningar av studieposter och sammanfattande resultat till ClinicalTrials.gov. Studieposter och rapporterade resultat granskas av National Library of Medicine (NLM) för att säkerställa att de uppfyller specifika kvalitetskontrollstandarder innan de publiceras på den offentliga webbplatsen.
Studera stora datum
Studiestart
1 juni 2010
Primärt slutförande (Faktisk)
1 augusti 2012
Avslutad studie (Faktisk)
1 augusti 2012
Studieregistreringsdatum
Först inskickad
2 juni 2010
Först inskickad som uppfyllde QC-kriterierna
3 juni 2010
Första postat (Uppskatta)
4 juni 2010
Uppdateringar av studier
Senaste uppdatering publicerad (Faktisk)
17 juni 2019
Senaste inskickade uppdateringen som uppfyllde QC-kriterierna
11 mars 2019
Senast verifierad
1 mars 2019
Mer information
Termer relaterade till denna studie
Ytterligare relevanta MeSH-villkor
Andra studie-ID-nummer
- 13945
- CP22-0901 (Annan identifierare: ImClone, LLC)
- I4Z-IE-JDEA (Annan identifierare: Eli Lilly and Company)
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