Combination Therapy for Patients With Untreated Metastatic Pancreatic Ductal Adenocarcinoma

A Phase II Pilot Trial of Nivolumab + Albumin-Bound Paclitaxel + Paricalcitol + Cisplatin + Gemcitabine (NAPPCG) In Patients With Previously Untreated Metastatic Pancreatic Ductal Adenocarcinoma

The purpose of this study is to find out if the study drugs nivolumab, albumin- bound paclitaxel, paricalcitol, cisplatin, and gemcitabine given together are safe and effective when combined to treat advanced pancreatic cancer.

Study Overview

• Status: Active, not recruiting
• Conditions: Untreated Metastatic Pancreatic Ductal Adenocarcinoma
• Intervention / Treatment: Drug: Nivolumab; Drug: Albumin-bound paclitaxel; Drug: Paricalcitol; Drug: Cisplatin; Drug: Gemcitabine

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85258
      • Clinical Trials Nurse Navigator

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Age ≥18 years of age .
2. Histologically or cytologically confirmed metastatic pancreatic ductal adenocarcinoma.
3. Capable of providing informed consent and complying with Trial procedures.
4. Karnofsky Performance Status (KPS) of ≥ 70%.
5. Life expectancy ≥ 12 weeks.
6. Measurable tumor lesions according to RECIST 1.1 criteria.
7. Women must not be able to become pregnant (e.g. post-menopausal for at least 1 year, surgically sterile, or practicing adequate birth control methods) for the duration of the study. Women of child bearing potential must have a negative serum or urine pregnancy test at the Screening Visit and be non-lactating. Both male and female patients of reproductive potential must agree to use a reliable method of birth control during the study.

Exclusion Criteria:

1. Patients must have received no previous radiotherapy, surgery, chemotherapy or investigational therapy for the treatment of metastatic disease. Prior treatments in the adjuvant setting with gemcitabine and/or 5-FU or gemcitabine administered as a radiation sensitizer are allowed, provided at least 6 months have elapsed since completion of the last dose and no lingering toxicities are present.
2. Palliative surgery and/or radiation treatment less than 4 weeks prior to initiation of study treatment.
3. Exposure to any investigational agent within 4 weeks prior to initiation of study treatment.
4. Evidence of central nervous system (CNS) metastasis (negative imaging study, if clinically indicated, within 4 weeks of Screening Visit).
5. History of other malignancies (except cured basal cell carcinoma, superficial bladder cancer or carcinoma in situ of the cervix) unless documented free of cancer for ≥5 years.
6. Laboratory values: Screening serum creatinine > upper limit of normal (ULN); total bilirubin > (ULN); alanine aminotransferase (ALT) and AST ≥ 2.5 ULN or ≥ 5.0×ULN if liver metastases are present; absolute neutrophil count <1,500/mm3, platelet concentration <100,000/mm3, hematocrit level <27% for females or <30% for males, or coagulation tests (prothrombin time [PT], partial thromboplastin time [PTT], International Normalized Ratio [INR]) >1.5×ULN unless on therapeutic doses of warfarin.
7. Current, serious, clinically significant cardiac arrhythmias as determined by the investigator.
8. History of HIV infection or active or chronic hepatitis B or C.
9. Active, clinically significant serious infection requiring treatment with antibiotics, anti-virals or anti-fungals.
10. Major surgery within 4 weeks prior to initiation of study treatment.
11. Any condition that might interfere with the patient's participation in the study or in the evaluation of the study results.
12. Any condition that is unstable and could jeopardize the patient's participation in the study.
13. Patient has a transplanted organ.
14. Patients with a history of autoimmune disease.
15. Prior PD-1 or PD-L1 therapy.
16. Patients taking any chemo or immunosuppressive steroids (equivalent to > 20 mg hydrocortisone per day).
17. Patients cannot have > Grade 1 pre-existing peripheral neuropathy (per CTCAE).

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Other: single arm; open label using combination therapy

Drug: Nivolumab; Nivolumab 240mg 240 mg as a 60 minute infusion on days 1, 15, 29 per 42 day cycle; Other Names: Opdivo; Drug: Albumin-bound paclitaxel; 125 mg/m2 over 30 minutes IV infusion on days 1, 8 and 22, 29 per 42 day cycle; Other Names: Abraxane; Drug: Paricalcitol; 25 micrograms IV on days 1,4,8,12,15,18,22,26,29,32,36,39 (+/-1 day allowed for dosing per 42 day cycle; Other Names: Zemplar; Drug: Cisplatin; 25 mg/m2 over 60 minutes IV infusion on days 1, 8 and 22, 29 per 42 day cycle; Other Names: Platinol; Drug: Gemcitabine; 1000 mg/m2 over 30 minutes IV infusion on days 1, 8 and 22, 29 per 42 day cycle; Other Names: Gemzar

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete response rate	Complete response rate as defined by CT scan using RECIST 1.1 criteria and CA 19-9 (or CA 125, or CEA if not expressers of CA 19-9) down to normal limits.When a complete response is documented, a PET scan will be obtained to confirm.	From date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0	Patients will be followed throughout their study participation and every 12 weeks following last dose of treatment until reported date of death.	From date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months

Collaborators and Investigators

• Sponsor: HonorHealth Research Institute
• Collaborators: Bristol-Myers Squibb; Lustgarten Foundation; Translational Genomics Research Institute
• Investigators: Principal Investigator: Erkut Borazanci, MD, HonorHealth Research Institute

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2016
• Primary Completion (Actual): April 11, 2023
• Study Completion (Estimated): December 1, 2023

Study Registration Dates

• First Submitted: April 19, 2016
• First Submitted That Met QC Criteria: April 25, 2016
• First Posted (Estimated): April 28, 2016

Study Record Updates

• Last Update Posted (Actual): August 15, 2023
• Last Update Submitted That Met QC Criteria: August 14, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Carcinoma; Neoplasms, Glandular and Epithelial; Adenocarcinoma; 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; Cisplatin; Nivolumab; Albumin-Bound Paclitaxel; Gemcitabine
• Other Study ID Numbers: NAPPCG-EB 2015-001