A Pilot Study of Perioperative Nivolumab and Paricalcitol to Target the Microenvironment in Resectable Pancreatic Cancer

The main purpose of this study is to look at the potential effects of paricalcitol (a drug similar to vitamin D) and nivolumab on pancreatic tumors in patients who are treated with gemcitabine and abraxane. The study will also look at the safety of including paricalcitol and nivolumab as part of the gemcitabine and abraxane chemotherapeutic regimen.

Study Overview

• Status: Terminated
• Conditions: Pancreatic Cancer
• Intervention / Treatment: Drug: Nivolumab; Drug: Nab-Paclitaxel; Drug: Gemcitabine; Drug: Paricalcitol

• Study Type: Interventional
• Enrollment (Actual): 3
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Abramson Cancer Center of the University of Pennsylvania

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Previously untreated, apparently resectable adenocarcinoma of the pancreas at registration.
• Age greater than or equal to 18 years
• ECOG performance status of 0-2.

• Standard laboratory criteria for hematologic, biochemical, and urinary indices within a range that, in the opinion of the physician, clinically supports enrollment of the subject on the trial.

  a. Note: subjects must have: Creatinine < 2xULN, Neutrophils >1.5x109/L, total bilirubin < 3xULN, AST <5xULN, ALT <5xULN, and Platelets >100,000/mm3

• Ability to provide written informed consent

Exclusion Criteria:

• Subjects with hypercalcemia (blood levels greater than 11.5 mg/dL). In subjects creatinine clearance <60mL/min, blood calcium levels must be 9.5 mg/dL or lower.

• Subjects who are currently pregnant, planning to become pregnant, or breast-feeding

  1. Females participants of child-bearing potential are required to use an effective contraception method (see Appendix A) or abstain from intercourse during treatment and for at least 5 months following the last dose
  2. Males participants with partners of child-bearing potential are required to use an effective contraception method (see Appendix A) or abstain from intercourse during treatment and for at least 5 months following the last dose 3. Subjects who, in the opinion of the physician, would not be clinically appropriate for receipt of the therapy regimen associated with participation 4. Subjects with contraindications to immune checkpoint therapy, as follows:
  1. Interstitial lung disease that is symptomatic or may interfere with the detection and management of suspected drug-related pulmonary toxicity
  2. Prior organ allograft or allogeneic bone marrow transplantation
  3. Pre-existing thyroid abnormality with thyroid function that cannot be maintained in the normal range with medication
  4. Active autoimmune disease, except for vitiligo, type 1 diabetes mellitus, asthma, atopic dermatitis, or endocrinopathies manageable by hormone replacement; other autoimmune conditions may be allowable at the discretion of the principal investigator

  5. Condition requiring systemic treatment with either corticosteroids

     • Systemic steroids at physiologic doses (equivalent to dose of oral prednisone 10 mg) are permitted. Steroids as anti-emetics for chemotherapy are strongly discouraged (see section 5.1.3)
     • Intranasal, inhaled, topical, intra-articular, and ocular corticosteroids with minimal systemic absorption are permitted

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A	Drug: Nivolumab; Before Surgery Wks 1 &3, After Surgery Wks 1 &3; Drug: Nab-Paclitaxel; Wks 1,2,3 before surgery and Wks 1, 2,3 after surgery; Drug: Gemcitabine; Wks 1,2,3 before surgery and Wks 1,2,3 after surgery; Drug: Paricalcitol; Wks 1,2,3, 4 before surgery and Wks 1,2,3 after surgery
Experimental: Arm B	Drug: Nivolumab; Before Surgery Wks 1 &3, After Surgery Wks 1 &3; Drug: Nab-Paclitaxel; Wks 1,2,3 before surgery and Wks 1, 2,3 after surgery; Drug: Gemcitabine; Wks 1,2,3 before surgery and Wks 1,2,3 after surgery

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Adverse Events	An adverse event (AE) was defined as any unfavorable symptom, sign, illness or experience that occurs at any dose and develops or worsens in severity during the course of the study. AEs were graded using the Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0.	18 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate	Objective response rate by RECIST v 1.1 after neoadjuvant chemotherapy. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Objective Response (OR) = CR + PR.	3 months
Progression-free Survival	Proportion of patients alive without progression 1 year from the start of study therapy	1 year
Proportion of Patients Undergoing Surgery	Proportion of patients who underwent surgical resection after receiving neoadjuvant therapy	3 months
Overall Survival	Overall survival 1 year after the initiation of study therapy	1 year
Proportion of Margin Negative Surgical Resections	Proportion of patients undergoing surgical resection with surgical margins uninvolved by tumor	3 months

Collaborators and Investigators

• Sponsor: Abramson Cancer Center at Penn Medicine
• Investigators: Principal Investigator: Peter O'Dwyer, MD, Abramson Cancer Center at Penn Medicine

Study record dates

Study Major Dates

• Study Start (Actual): July 29, 2020
• Primary Completion (Actual): April 18, 2022
• Study Completion (Actual): April 18, 2022

Study Registration Dates

• First Submitted: April 24, 2018
• First Submitted That Met QC Criteria: May 7, 2018
• First Posted (Actual): May 8, 2018

Study Record Updates

• Last Update Posted (Actual): March 15, 2024
• Last Update Submitted That Met QC Criteria: March 14, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Endocrine System Diseases; Digestive System Neoplasms; Endocrine Gland Neoplasms; Pancreatic Diseases; Pancreatic Neoplasms; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Paclitaxel; Nivolumab; Gemcitabine
• Other Study ID Numbers: UPCC 22217

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No