Ignite Creation Date:
2025-12-25 @ 3:46 AM
Ignite Modification Date:
2026-03-12 @ 3:31 AM
Study NCT ID:
NCT02930902
Status:
COMPLETED
Last Update Posted:
2023-02-09
First Post:
2016-10-10
Is Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Pembrolizumab and Paricalcitol With or Without Chemotherapy in Patients With Pancreatic Cancer That Can Be Removed by Surgery
Sponsor:
M.D. Anderson Cancer Center
Organization:
Study Overview
Official Title:
A Preoperative Phase 1B Study to Assess the Safety and the Immunological Effect of Pembrolizumab (Keytruda®) in Combination With Paricalcitol With or Without Chemotherapy in Patients With Resectable Pancreatic Cancer
Status:
COMPLETED
Status Verified Date:
2023-02
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 Ib trial studies the side effects and best way to give pembrolizumab and paricalcitol with or without chemotherapy in patients with pancreatic cancer that can be removed by surgery. Monoclonal antibodies, such as pembrolizumab, may find tumor cells and help carry tumor-killing substances to them. Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving pembrolizumab and paricalcitol with or without chemotherapy before surgery may help to control the disease.
Detailed Description:
PRIMARY OBJECTIVES:
I. To determine the safety of neoadjuvant pembrolizumab in combination with paricalcitol with or without gemcitabine and nab-paclitaxel for the treatment of resectable pancreatic cancer.
II. To estimate the number of tumor infiltrating lymphocytes (TILs) in resected pancreatic cancer subjects receiving neoadjuvant pembrolizumab in combination with paricalcitol with or without gemcitabine and nab-paclitaxel.
SECONDARY OBJECTIVES:
I. To estimate the resection rate and pathological response of resectable pancreatic cancer treated with neoadjuvant pembrolizumab in combination with paricalcitol with or without gemcitabine and nab-paclitaxel.
EXPLORATORY CORRELATIVE OBJECTIVES:
I. To estimate the disease free survival (DFS) of resectable pancreatic cancer subjects treated with neoadjuvant pembrolizumab in combination with paricalcitol with or without gemcitabine and nab-paclitaxel.
II. To estimate the overall survival (OS) of subjects with resectable pancreatic cancer who received neoadjuvant pembrolizumab in combination with paricalcitol with or without gemcitabine and nab-paclitaxel.
III. To enumerate CD8+ and CD8+ CD45RO+ cells within and around tumor cell nests, and characterize immunotypes based on distribution of T cells relative to intratumoral vasculature post-neoadjuvant treatment.
IV. To evaluate PD-L1 expression on tumor samples pre- and post-neoadjuvant treatment.
V. To estimate changes in different subsets of T- cells in the peripheral blood pre, during and post-neoadjuvant treatment.
VI. To identify immune signature based on gene expression profiling in tumor samples that may correlate with clinical response in pancreatic cancer patients.
VII. Compare TILs in resected specimen to historical controls of untreated and treated samples.
VIII. To explore the relationship between genomic alterations and treatment administered.
OUTLINE: Patients are assigned to 1 of 2 arms.
ARM A: Patients receive pembrolizumab intravenously (IV) over 30 minutes on day 1 of each course and paricalcitol IV over 15 minutes on days 1, 8, and 15. Treatment repeats every 21 days for up to 2 courses in the absence of disease progression or unacceptable toxicity. Surgical resection is performed within 1 week and up to 4 weeks from last dose of paricalcitol.
ARM B: Patients receive pembrolizumab and paricalcitol as in Arm A. Patients also receive gemcitabine hydrochloride IV over 30 minutes and nab-paclitaxel IV over 30-40 minutes on days 1, 8, and 15 of course 1 in the absence of disease progression or unacceptable toxicity. Surgical resection is performed within 1 week and up to 4 weeks from last dose of paricalcitol.
After completion of study treatment, patients are followed up at 30 days, every 4 months for 1 year, then every 6 months for 2 years.
I. To determine the safety of neoadjuvant pembrolizumab in combination with paricalcitol with or without gemcitabine and nab-paclitaxel for the treatment of resectable pancreatic cancer.
II. To estimate the number of tumor infiltrating lymphocytes (TILs) in resected pancreatic cancer subjects receiving neoadjuvant pembrolizumab in combination with paricalcitol with or without gemcitabine and nab-paclitaxel.
SECONDARY OBJECTIVES:
I. To estimate the resection rate and pathological response of resectable pancreatic cancer treated with neoadjuvant pembrolizumab in combination with paricalcitol with or without gemcitabine and nab-paclitaxel.
EXPLORATORY CORRELATIVE OBJECTIVES:
I. To estimate the disease free survival (DFS) of resectable pancreatic cancer subjects treated with neoadjuvant pembrolizumab in combination with paricalcitol with or without gemcitabine and nab-paclitaxel.
II. To estimate the overall survival (OS) of subjects with resectable pancreatic cancer who received neoadjuvant pembrolizumab in combination with paricalcitol with or without gemcitabine and nab-paclitaxel.
III. To enumerate CD8+ and CD8+ CD45RO+ cells within and around tumor cell nests, and characterize immunotypes based on distribution of T cells relative to intratumoral vasculature post-neoadjuvant treatment.
IV. To evaluate PD-L1 expression on tumor samples pre- and post-neoadjuvant treatment.
V. To estimate changes in different subsets of T- cells in the peripheral blood pre, during and post-neoadjuvant treatment.
VI. To identify immune signature based on gene expression profiling in tumor samples that may correlate with clinical response in pancreatic cancer patients.
VII. Compare TILs in resected specimen to historical controls of untreated and treated samples.
VIII. To explore the relationship between genomic alterations and treatment administered.
OUTLINE: Patients are assigned to 1 of 2 arms.
ARM A: Patients receive pembrolizumab intravenously (IV) over 30 minutes on day 1 of each course and paricalcitol IV over 15 minutes on days 1, 8, and 15. Treatment repeats every 21 days for up to 2 courses in the absence of disease progression or unacceptable toxicity. Surgical resection is performed within 1 week and up to 4 weeks from last dose of paricalcitol.
ARM B: Patients receive pembrolizumab and paricalcitol as in Arm A. Patients also receive gemcitabine hydrochloride IV over 30 minutes and nab-paclitaxel IV over 30-40 minutes on days 1, 8, and 15 of course 1 in the absence of disease progression or unacceptable toxicity. Surgical resection is performed within 1 week and up to 4 weeks from last dose of paricalcitol.
After completion of study treatment, patients are followed up at 30 days, every 4 months for 1 year, then every 6 months for 2 years.
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?: