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

Early Phase 1

Terminated

• Conditions: Pancreatic Cancer
• Interventions: Drug: Nivolumab; Drug: Nab-Paclitaxel; Drug: Gemcitabine; Drug: Paricalcitol

• Registration Number: NCT03519308
• Lead Sponsor: Abramson Cancer Center at Penn Medicine

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2018-04-24
• Study First Submitted QC: 2018-05-07
• Study First Posted: 2018-05-08
• Study Start: 2020-07-29
• Primary Completion: 2022-04-18
• Study Completion: 2022-04-18
• Results First Submitted: 2023-09-29
• Status Verified: 2024-03
• Results First Submitted QC: 2024-03-14
• Last Update Submitted: 2024-03-14
• Results First Posted: 2024-03-15
• Last Update Posted: 2024-03-15

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 3

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:
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  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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Arm A	Nab-Paclitaxel	-
Arm B	Nab-Paclitaxel	-
Arm A	Paricalcitol	-
Arm B	Nivolumab	-
Arm A	Nivolumab	-
Arm A	Gemcitabine	-
Arm B	Gemcitabine	-

Primary Outcome Measures

Name	Time	Method
Number of Adverse Events	18 months	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.

Secondary Outcome Measures

Name	Time	Method
Overall Survival	1 year	Overall survival 1 year after the initiation of study therapy
Objective Response Rate	3 months	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.
Progression-free Survival	1 year	Proportion of patients alive without progression 1 year from the start of study therapy
Proportion of Patients Undergoing Surgery	3 months	Proportion of patients who underwent surgical resection after receiving neoadjuvant therapy
Proportion of Margin Negative Surgical Resections	3 months	Proportion of patients undergoing surgical resection with surgical margins uninvolved by tumor

Trial Locations

Locations (1)

Abramson Cancer Center of the University of Pennsylvania; 🇺🇸 Philadelphia, Pennsylvania, United States