Pembrolizumab And Paricalcitol With Or Without Chemotherapy In Patients With Pancreatic Cancer That Can Be Removed By Surgery

Study Overview

Pembrolizumab and Paricalcitol With or Without Chemotherapy in Patients With Pancreatic Cancer That Can Be Removed by Surgery

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.

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.

Resectable Pancreatic Carcinoma
Stage I Pancreatic Cancer AJCC v6 and v7
Stage IA Pancreatic Cancer AJCC v6 and v7
Stage IB Pancreatic Cancer AJCC v6 and v7
Stage II Pancreatic Cancer AJCC v6 and v7
Stage IIA Pancreatic Cancer AJCC v6 and v7
Stage IIB Pancreatic Cancer AJCC v6 and v7

DRUG: Gemcitabine Hydrochloride
OTHER: Laboratory Biomarker Analysis
DRUG: Nab-paclitaxel
DRUG: Paricalcitol
BIOLOGICAL: Pembrolizumab
PROCEDURE: Therapeutic Conventional Surgery

2016-0378
NCI-2016-01937 (REGISTRY Identifier) (REGISTRY: CTRP (Clinical Trial Reporting Program))
2016-0378 (OTHER Identifier) (OTHER: M D Anderson Cancer Center)

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2016-10-10	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2023-02-07
First Submitted that Met QC Criteria 2016-10-11	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ACTUAL) 2023-02-09
First Posted (ACTUAL) 2016-10-12	Results First Posted N/A	Last Verified 2023-02

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Non Randomized

Interventional Model:
Parallel

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
ACTIVE_COMPARATOR: Arm A (pembrolizumab, paricalcitol) Patients receive pembrolizumab 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. Surgica	OTHER: Laboratory Biomarker Analysis Correlative studies DRUG: Paricalcitol Given IV BIOLOGICAL: Pembrolizumab Given IV PROCEDURE: Therapeutic Conventional Surgery Undergo surgical resection of tumor
EXPERIMENTAL: Arm B (pembrolizumab, paricalcitol, chemotherapy) 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	DRUG: Gemcitabine Hydrochloride Given IV OTHER: Laboratory Biomarker Analysis Correlative studies DRUG: Nab-paclitaxel Given IV DRUG: Paricalcitol Given IV BIOLOGICAL: Pembrolizumab Given IV PROCEDURE: Therapeutic Conventional Surgery Undergo surgical resection of tumor

Participant Group/Arm

Intervention/Treatment

ACTIVE_COMPARATOR: Arm A (pembrolizumab, paricalcitol)

Patients receive pembrolizumab 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. Surgica

OTHER: Laboratory Biomarker Analysis

Correlative studies

DRUG: Paricalcitol

Given IV

BIOLOGICAL: Pembrolizumab

Given IV

PROCEDURE: Therapeutic Conventional Surgery

Undergo surgical resection of tumor

EXPERIMENTAL: Arm B (pembrolizumab, paricalcitol, chemotherapy)

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

DRUG: Gemcitabine Hydrochloride

Given IV

OTHER: Laboratory Biomarker Analysis

Correlative studies

DRUG: Nab-paclitaxel

Given IV

DRUG: Paricalcitol

Given IV

BIOLOGICAL: Pembrolizumab

Given IV

PROCEDURE: Therapeutic Conventional Surgery

Undergo surgical resection of tumor

Primary Outcome Measures	Measure Description	Time Frame
Incidence of toxicities as defined by Common Terminology Criteria for Adverse Events version 4.0	Incidence will be descriptive.	Up to 11 weeks

Secondary Outcome Measures	Measure Description	Time Frame
Resection rate	Summary statistics will be used.	Up to 7 weeks (within 1 week of end of neoadjuvant treatment)

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

Be willing and able to provide written informed consent for the trial
Patients must have potentially resectable pancreatic carcinoma and have agreed to undergo surgical resection at Monroe Dunaway (MD) Anderson Cancer Center if operable; they will have undergone staging (physical examination, contrast enhanced computed tomography [CT] or magnetic resonance imaging [MRI] [if CT contraindicated] to determine resectability)
Patients with Eastern Cooperative Oncology Group (ECOG) performance status 0-1 are eligible
Have histologically or cytologically confirmed diagnosis of pancreatic carcinoma
Have no known metastases
Previous systemic chemotherapy or radiation for pancreatic cancer is not allowed
In subjects requiring biliary decompression, biliary stent or drainage using percutaneous transhepatic cholangiogram (PTC) are allowed
Patients must have no fever or evidence of infection or other coexisting medical condition that would preclude administration of study drugs; patients with uncontrolled congestive heart failure, unstable angina and myocardial infarction within 3 months will be excluded
Have a negative urine or serum pregnancy test within 72 hours prior to receiving the first dose of study medication, pembrolizumab (cycle 1, day 1) (female subjects of childbearing potential); if the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
Be willing to use an adequate method of contraception for the course of the study through 120 days after the last dose of study medication (male and female subjects of childbearing potential; Note: abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject; acceptable methods of contraception are as follows: single method (one of the following is acceptable): intrauterine device (IUD), vasectomy of a female subject's male partner, contraceptive rod implanted into the skin; combination method (requires use of two of the following): diaphragm with spermicide (cannot be used in conjunction with cervical cap/spermicide), cervical cap with spermicide (nulliparous women only), contraceptive sponge (nulliparous women only), male condom or female condom (cannot be used together), hormonal contraceptive: oral contraceptive pill (estrogen/progestin pill or progestin-only pill), contraceptive skin patch, vaginal contraceptive ring, or subcutaneous contraceptive injection; abstinence is acceptable if this is the usual lifestyle and preferred contraception method for the subject
Demonstrate adequate organ function; all screening laboratory tests should be performed within 7 days of treatment initiation
Patients must have tumor tissue available from a diagnostic or other pre-treatment biopsy of the tumor that is sufficient for tissue analysis as follows:

Hematoxylin and eosin (H&E) analysis shows sufficient malignant cell staining of the tissue
Formalin-fixed paraffin-embedded (FFPE) cell block that provides a minimum of 10 unstained slides
Cell block may be created from multiple-pass fine needle aspiration (FNA) if core needle biopsy (CNB) is not feasible

Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy, herbal/complementary oral or IV medicine, or used an investigation device within 4 weeks of the first dose of treatment
Major cardiovascular or pulmonary comorbidity that precludes use of general anesthesia (NYHA [New York Heart Association] class III and IV)
Had prior systemic therapy for pancreatic cancer
Has active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs); replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment
Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment; the use of physiologic doses of corticosteroids may be approved after consultation with the principal investigator (PI) and Merck
Has a diagnosed additional malignancy within 5 years prior to first dose of study treatment with the exception of curatively treated basal cell carcinoma of the skin, squamous cell carcinoma of the skin and/or curatively resected in situ cervical and/or breast cancers
Has radiographically detectable (even if asymptomatic and/or previously treated) central nervous system (CNS) metastases and/or carcinomatous meningitis as assessed by local site investigator and radiology review
Has a known history of, or any evidence of, interstitial lung disease or (non-infectious) pneumonitis that required steroids or there is current pneumonitis
Has an active infection requiring systemic therapy
Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator, including dialysis
Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the screening visit through 120 days after the last dose of trial treatment
Has received prior immunotherapy including anti-PD-1, anti-PD-L1, or anti-PD-L2 agents, or if the subject has previously participated in Merck pembrolizumab clinical trials
Has a known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies)
Has documented active hepatitis B (e.g., hepatitis B surface antigen [HBsAg] reactive) or hepatitis C (e.g., hepatitis C virus [HCV] ribonucleic acid [RNA] [qualitative] is detected); in patients without a known history of hepatitis B or C, serologies should be obtained at screening
Has received a live vaccine within 30 days of planned start of study therapy (cycle 1, day 1); Note: the killed virus vaccines used for seasonal influenza vaccines for injection are allowed; however intranasal influenza vaccines (e.g., FluMist) are live attenuated vaccines and are not allowed
Has laboratory evidence of hypercalcemia (>= 11 mg/dl [in presence of normal albumin]) and/or hyperphosphatemia (>= 5.5)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

National Cancer Institute (NCI)

Investigators

PRINCIPAL_INVESTIGATOR: Brandon G Smaglo, MD, M.D. Anderson Cancer Center

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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