Combination Therapy for Patients With Untreated Metastatic Pancreatic Ductal Adenocarcinoma

• Sponsor: HonorHealth Research Institute
• Collaborators: Translational Genomics Research Institute; Bristol-Myers Squibb
• Information provided by (Responsible Party): HonorHealth Research Institute

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Untreated Metastatic Pancreatic Ductal Adenocarcinoma	Drug: Nivolumab; Drug: Albumin-bound paclitaxel; Drug: Paricalcitol; Drug: Cisplatin; Drug: Gemcitabine	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 10 participants
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Pilot Trial of Nivolumab + Albumin-Bound Paclitaxel + Paricalcitol + Cisplatin + Gemcitabine (NAPPCG) In Patients With Previously Untreated Metastatic Pancreatic Ductal Adenocarcinoma
• Study Start Date: April 2016
• Estimated Primary Completion Date: July 2019
• Estimated Study Completion Date: July 2020

Arms and Interventions

Arm

Intervention/treatment

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 Name: 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 Name: 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 Name: Zemplar; Drug: Cisplatin; 25 mg/m2 over 60 minutes IV infusion on days 1, 8 and 22, 29 per 42 day cycle; Drug: Gemcitabine; 1000 mg/m2 over 30 minutes IV infusion on days 1, 8 and 22, 29 per 42 day cycle; Other Name: Gemzar

Outcome Measures

Primary Outcome Measures :

1. Complete response rate [ Time Frame: 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 ]
   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.

Secondary Outcome Measures :

1. Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 [ Time Frame: 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 ]
   Patients will be followed throughout their study participation and every 12 weeks following last dose of treatment until reported date of death.

Eligibility Criteria

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

Criteria

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).

Contacts and Locations

Contacts

Contact: Joyce Schaffer, MSN, AOCNS; 480-323-1339 (option #2); Joyce.Schaffer@HonorHealth.com

Locations

United States, Arizona

HonorHealth Research Institute; Recruiting

Scottsdale, Arizona, United States, 85258

Contact: Joyce Schaffer, MSN, AOCNS 480-323-1339 ext option #2 Joyce.Schaffer@HonorHealth.com

Principal Investigator: Erkut Borazanci, MD

Sponsors and Collaborators

HonorHealth Research Institute

Translational Genomics Research Institute

Bristol-Myers Squibb

Investigators

• Principal Investigator: Erkut Borazanci, MD; HonorHealth Research Institute

More Information

• Responsible Party: HonorHealth Research Institute
• ClinicalTrials.gov Identifier: NCT02754726 History of Changes
• Other Study ID Numbers: NAPPCG-EB 2015-001
• First Posted: April 28, 2016
• Last Update Posted: October 10, 2018
• Last Verified: January 2018

Additional relevant MeSH terms:

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Gemcitabine; Paclitaxel; Albumin-Bound Paclitaxel; Cisplatin; Nivolumab; Antineoplastic Agents, Phytogenic; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antiviral Agents; Anti-Infective Agents; Enzyme Inhibitors; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Antineoplastic Agents, Immunological