Ignite Creation Date:
2025-12-25 @ 12:20 AM
Ignite Modification Date:
2026-01-04 @ 5:58 AM
Study NCT ID:
NCT03326258
Status:
WITHDRAWN
Last Update Posted:
2018-07-18
First Post:
2017-10-30
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Glembatumumab Vedotin, Nivolumab, and Ipilimumab in Treating Patients With Advanced Metastatic Solid Tumors That Cannot Be Removed by Surgery
Sponsor:
National Cancer Institute (NCI)
Organization:
Study Overview
Official Title:
Phase Ib/II Clinical Trial of Glembatumumab Vedotin and Nivolumab in Advanced Solid Tumors
Status:
WITHDRAWN
Status Verified Date:
2018-05
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
The study itself was Disapproved on 04/20/2018 and will not be moving forward.
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This phase Ib/II trial studies the best dose of glembatumumab vedotin when giving together with nivolumab and ipilimumab in treating patients with solid tumor that has spread to other places in the body and cannot be removed by surgery. Monoclonal antibodies, such as glembatumumab vedotin, nivolumab, and ipilimumab, may interfere with the ability of tumor cells to grow and spread.
Detailed Description:
PRIMARY OBJECTIVES:
I. To determine the recommended phase 2 dose (RP2D) for the combination of glembatumumab vedotin and nivolumab in patients with solid tumors. (Phase Ib) II. To evaluate the antitumor activity of the combination in 4 expansion cohorts (melanoma, uveal melanoma, GPNMB overexpressing triple negative breast cancer \[TNBC\], other GPNMB overexpressing solid tumors) as measured by overall response by Immune-Modified Response Evaluation Criteria in Solid Tumors (iRECIST)/Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. (Phase II)
SECONDARY OBJECTIVES:
I. To characterize the safety and toxicity profile of the combination. II. To evaluate the clinical benefit rate (no disease progression within 6 months), progression free survival (PFS), and overall survival (OS) in patients receiving the combination treatment.
III. To evaluate the pharmacokinetics (PK) of glembatumumab vedotin and nivolumab in combination in serum and in mononuclear phagocyte system (MPS) cells in peripheral blood mononuclear cells.
IV. Profile differences in the type, number and density of Fc-receptors (FcgammaR) on MPS cells in blood of patients prior to and after administration of glembatumumab vedotin and nivolumab as a method to evaluate the factors affecting PK and pharmacodynamics (PD) variability and mechanisms of drug-drug interactions.
V. Characterize differences in chemokines (CCL2 and CCL5) and other cytokines in blood of patients prior to and after administration of glembatumumab vedotin and nivolumab as a method to evaluate the factors affecting PK and PD variability and mechanisms of drug-drug interactions.
VI. To evaluate the pharmacodynamic (PD) effects of the combination in plasma and tissue biomarkers.
OUTLINE:
Patients receive glembatumumab vedotin intravenously (IV) over 90 minutes and nivolumab IV over 60 minutes on day 8 of course 1 and on day 1 of subsequent courses. Patients in melanoma expanded cohort also receive ipilimumab IV over 90 minutes on day 1. Treatment with ipilimumab repeats every 21 days for 4 courses in the absence of disease progression or unaccepted toxicity and courses with glembatumumab vedotin and nivolumab repeat every 21 days in the absence of disease progression or unaccepted toxicity.
After completion of study treatment, patients are followed up for 4 weeks and then at 30 and 70 days.
I. To determine the recommended phase 2 dose (RP2D) for the combination of glembatumumab vedotin and nivolumab in patients with solid tumors. (Phase Ib) II. To evaluate the antitumor activity of the combination in 4 expansion cohorts (melanoma, uveal melanoma, GPNMB overexpressing triple negative breast cancer \[TNBC\], other GPNMB overexpressing solid tumors) as measured by overall response by Immune-Modified Response Evaluation Criteria in Solid Tumors (iRECIST)/Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. (Phase II)
SECONDARY OBJECTIVES:
I. To characterize the safety and toxicity profile of the combination. II. To evaluate the clinical benefit rate (no disease progression within 6 months), progression free survival (PFS), and overall survival (OS) in patients receiving the combination treatment.
III. To evaluate the pharmacokinetics (PK) of glembatumumab vedotin and nivolumab in combination in serum and in mononuclear phagocyte system (MPS) cells in peripheral blood mononuclear cells.
IV. Profile differences in the type, number and density of Fc-receptors (FcgammaR) on MPS cells in blood of patients prior to and after administration of glembatumumab vedotin and nivolumab as a method to evaluate the factors affecting PK and pharmacodynamics (PD) variability and mechanisms of drug-drug interactions.
V. Characterize differences in chemokines (CCL2 and CCL5) and other cytokines in blood of patients prior to and after administration of glembatumumab vedotin and nivolumab as a method to evaluate the factors affecting PK and PD variability and mechanisms of drug-drug interactions.
VI. To evaluate the pharmacodynamic (PD) effects of the combination in plasma and tissue biomarkers.
OUTLINE:
Patients receive glembatumumab vedotin intravenously (IV) over 90 minutes and nivolumab IV over 60 minutes on day 8 of course 1 and on day 1 of subsequent courses. Patients in melanoma expanded cohort also receive ipilimumab IV over 90 minutes on day 1. Treatment with ipilimumab repeats every 21 days for 4 courses in the absence of disease progression or unaccepted toxicity and courses with glembatumumab vedotin and nivolumab repeat every 21 days in the absence of disease progression or unaccepted toxicity.
After completion of study treatment, patients are followed up for 4 weeks and then at 30 and 70 days.
Study Oversight
Has Oversight DMC:
False
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
Secondary ID Infos
| Secondary ID | Type | Domain | Link | View |
|---|---|---|---|---|
| NCI-2017-01979 | REGISTRY | CTRP (Clinical Trial Reporting Program) | View | |
| 10157 | OTHER | Duke University - Duke Cancer Institute LAO | View | |
| 10157 | OTHER | CTEP | View | |
| UM1CA186704 | NIH | None | https://reporter.nih.gov/quic… | View |