Combination Therapy for Patients With Untreated Metastatic Pancreatic Ductal Adenocarcinoma

Study Overview
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Brief Summary
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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.

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

Conditions
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Untreated Metastatic Pancreatic Ductal Adenocarcinoma

Intervention / Treatment
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* Drug: Nivolumab
* Drug: Albumin-bound paclitaxel
* Drug: Paricalcitol
* Drug: Cisplatin
* Drug: Gemcitabine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥18 years of age . Histologically or cytologically confirmed metastatic pancreatic ductal adenocarcinoma. Capable of providing informed consent and complying with Trial procedures. Karnofsky Performance Status (KPS) of ≥ 70%. Life expectancy ≥ 12 weeks. Measurable tumor lesions according to RECIST 1.1 criteria. 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: 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. Palliative surgery and/or radiation treatment less than 4 weeks prior to initiation of study treatment. Exposure to any investigational agent within 4 weeks prior to initiation of study treatment. Evidence of central nervous system (CNS) metastasis (negative imaging study, if clinically indicated, within 4 weeks of Screening Visit). 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. 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. Current, serious, clinically significant cardiac arrhythmias as determined by the investigator. History of HIV infection or active or chronic hepatitis B or C. Active, clinically significant serious infection requiring treatment with antibiotics, anti-virals or anti-fungals. Major surgery within 4 weeks prior to initiation of study treatment. Any condition that might interfere with the patient's participation in the study or in the evaluation of the study results. Any condition that is unstable and could jeopardize the patient's participation in the study. Patient has a transplanted organ. Patients with a history of autoimmune disease. Prior PD-1 or PD-L1 therapy. Patients taking any chemo or immunosuppressive steroids (equivalent to > 20 mg hydrocortisone per day). Patients cannot have > Grade 1 pre-existing peripheral neuropathy (per CTCAE).

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: single arm<br>open label using combination therapy | Drug: Nivolumab<br>* Nivolumab 240mg 240 mg as a 60 minute infusion on days 1, 15, 29 per 42 day cycle<br>* Other names: Opdivo;Drug: Albumin-bound paclitaxel<br>* 125 mg/m2 over 30 minutes IV infusion on days 1, 8 and 22, 29 per 42 day cycle<br>* Other names: Abraxane;Drug: Paricalcitol<br>* 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<br>* Other names: Zemplar;Drug: Cisplatin<br>* 25 mg/m2 over 60 minutes IV infusion on days 1, 8 and 22, 29 per 42 day cycle<br>* Other names: Platinol;Drug: Gemcitabine<br>* 1000 mg/m2 over 30 minutes IV infusion on days 1, 8 and 22, 29 per 42 day cycle<br>* Other names: Gemzar;|

What is the study measuring?
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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 |