Ignite Creation Date:
2025-12-25 @ 2:02 AM
Ignite Modification Date:
2026-03-03 @ 12:34 AM
Study NCT ID:
NCT03021460
Status:
ACTIVE_NOT_RECRUITING
Last Update Posted:
2025-08-19
First Post:
2017-01-12
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Pembrolizumab and Ibrutinib in Treating Patients With Stage III-IV Melanoma That Cannot Be Removed by Surgery
Sponsor:
Mayo Clinic
Organization:
Study Overview
Official Title:
Phase I Study of Pembrolizumab in Combination With Ibrutinib in the Treatment of Unresectable or Metastatic Melanoma
Status:
ACTIVE_NOT_RECRUITING
Status Verified Date:
2025-08
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This phase I trial studies the best dose of ibrutinib when given together with pembrolizumab in treating patients with stage III-IV melanoma that cannot be removed by surgery. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Ibrutinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving pembrolizumab and ibrutinib may work better in treating patients with melanoma.
Detailed Description:
PRIMARY OBJECTIVES:
I. To determine the maximum tolerated dose of ibrutinib in combination with pembrolizumab in patients with advanced melanoma. (Phase I) II. To estimate the overall response rate treated at the maximum tolerated dose of ibrutinib in combination with pembrolizumab in patients with advanced melanoma. (Dose expansion cohort)
SECONDARY OBJECTIVES:
I. To assess the safety and adverse-event profiles of combination of ibrutinib with pembrolizumab in patients with advanced melanoma.
II. To evaluate the overall response rate (ORR) in patients advanced melanoma receiving ibrutinib and pembrolizumab.
III. To evaluate the duration of response, progression-free survival (PFS), and overall survival (OS) in patients with advanced melanoma receiving ibrutinib and pembrolizumab.
IV. To assess the effect of treatment with ibrutinib and pembrolizumab on Th1/Th2 immune polarity.
EXPLORATORY OBJECTIVES:
I. To assess the CD8 T cell response to multiple melanoma-associated antigens, and to correlate CD8 T cell responses with changes in Th1/Th2 immune polarity.
II. To assess changes in plasma cytokines induced by treatment with ibrutinib and pembrolizumab.
III. To assess the change in potential biomarkers, such as tumor-bound and soluble PD-L1 levels and tumor-infiltrating lymphocytes, that may correlate with treatment responses.
OUTLINE: This is a dose-escalation study of ibrutinib.
Patients receive ibrutinib orally (PO) daily on days 1-28 of cycle 1 and days 1-21 of cycle 2 and subsequent cycles. Patients also receive pembrolizumab intravenously (IV) over 30 minutes on day 8 of cycle 1 and day 1 of cycle 2 and subsequent cycles. Cycle 1 continues for 28 days and subsequent cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 6 months for 5 years.
I. To determine the maximum tolerated dose of ibrutinib in combination with pembrolizumab in patients with advanced melanoma. (Phase I) II. To estimate the overall response rate treated at the maximum tolerated dose of ibrutinib in combination with pembrolizumab in patients with advanced melanoma. (Dose expansion cohort)
SECONDARY OBJECTIVES:
I. To assess the safety and adverse-event profiles of combination of ibrutinib with pembrolizumab in patients with advanced melanoma.
II. To evaluate the overall response rate (ORR) in patients advanced melanoma receiving ibrutinib and pembrolizumab.
III. To evaluate the duration of response, progression-free survival (PFS), and overall survival (OS) in patients with advanced melanoma receiving ibrutinib and pembrolizumab.
IV. To assess the effect of treatment with ibrutinib and pembrolizumab on Th1/Th2 immune polarity.
EXPLORATORY OBJECTIVES:
I. To assess the CD8 T cell response to multiple melanoma-associated antigens, and to correlate CD8 T cell responses with changes in Th1/Th2 immune polarity.
II. To assess changes in plasma cytokines induced by treatment with ibrutinib and pembrolizumab.
III. To assess the change in potential biomarkers, such as tumor-bound and soluble PD-L1 levels and tumor-infiltrating lymphocytes, that may correlate with treatment responses.
OUTLINE: This is a dose-escalation study of ibrutinib.
Patients receive ibrutinib orally (PO) daily on days 1-28 of cycle 1 and days 1-21 of cycle 2 and subsequent cycles. Patients also receive pembrolizumab intravenously (IV) over 30 minutes on day 8 of cycle 1 and day 1 of cycle 2 and subsequent cycles. Cycle 1 continues for 28 days and subsequent cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 6 months for 5 years.
Study Oversight
Has Oversight DMC:
True
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?:
False
Is an FDA AA801 Violation?: