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Paclitaxel Protein Bound Plus Cisplatin Plus Gemcitabine and Paricalcitol for Pancreatic Adenocarcinoma (NABPLAGEMD) (NABPLAGEMD)

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ClinicalTrials.gov Identifier: NCT03415854
Recruitment Status : Recruiting
First Posted : January 30, 2018
Last Update Posted : August 6, 2019
Sponsor:
Collaborators:
Barts Cancer Institute
Abramson Cancer Center of the University of Pennsylvania
Salk Institute for Biological Studies
Mayo Clinic
Princeton University
Imaging Endpoints
Translational Genomics Research Institute
Stand Up To Cancer
Cancer Research UK
Lustgarten Foundation
University of California, San Diego
Information provided by (Responsible Party):
HonorHealth Research Institute

Brief Summary:
The purpose of this study is to determine if the combination of paclitaxel protein bound, gemcitabine, cisplatin, paricalcitol are effective in individuals with previously untreated metastatic pancreatic cancer.

Condition or disease Intervention/treatment Phase
Pancreatic Cancer Pancreatic Ductal Adenocarcinoma Pancreatic Adenocarcinoma Pancreas Metastases Adenocarcinoma Drug: Paricalcitol (Zemplar) Phase 2

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 14 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Pilot Trial Of Paclitaxel Protein Bound Plus Cisplatin Plus Gemcitabine and the Addition Of Paricalcitol Upon Disease Progression in Patients With Previously Untreated Metastatic Pancreatic Ductal Adenocarcinoma (NABPLAGEMD)
Actual Study Start Date : January 31, 2018
Estimated Primary Completion Date : July 15, 2020
Estimated Study Completion Date : December 15, 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Paricalcitol (Zemplar)
Participants will be treated with the regimen according to the study protocol. Participants will complete 3 cycles (cycle is 21 days) and then will be evaluated for CA19-9 normalization and undergo imaging to determine response, if any.
Drug: Paricalcitol (Zemplar)
combination therapy
Other Names:
  • Cisplatin (Platinol)
  • Paclitaxel Protein Bound (Abraxane)
  • Gemcitabine (Gemzar)




Primary Outcome Measures :
  1. Pathologic Complete Response Rate [ Time Frame: At the end of 3 cycles (each cycle is 21 days) ]
    Participants will have an MRI completed after 3 cycles to determine if the tumor has responded to treatment. RECIST 1.1 criteria will be used to evaluate response. A confirmatory positron emission tomography (PET) scan may be ordered to confirm complete response.


Secondary Outcome Measures :
  1. Carbohydrate Antigen 19-9 (CA19-9) value [ Time Frame: At the end of each cycle (each cycle is 21 days) ]
    Laboratory testing will be used to determine if the CA19-9 value has normalized after each cycle of treatment.

  2. changes in circulating biomarkers induced by paricalcitol [ Time Frame: At the end of each cycle (each cycle is 21 days) ]
    Laboratory testing will be used to determine any changes in circulating biomarkers induced by paricalcitol. Biomarkers to be tested include: Stromal content (collagen and hyaluronan), CD31 (cluster of differentiation 31) staining, PD-1(programmed cell death-1) / PDl-1 (protein disulfide isomerase) staining and expression, IHC (Immunohistochemistry) evaluation of key immune cell populations (cytotoxic T Cells, TAMs (tumor-associated macrophages), MDSCs (myeloid-derived suppressor cells), and Tregs (regulatory T cells in cancer)), clonality of intra-tumoral T cells by TSR (tumor stroma ratio) sequencing (a measure of intratumoral response), expression of VDR (vitamin D receptor) regulated inflammatory gene (IL6 (interleukin 6), CXCL1 (chemokine (C-X-C motif) ligand 1), CSF2 (colony stimulating factor 2), CXCLR(chemokine (C-X-C motif) receptor)), VDR and CYP24A1 (cytochrome P450 family 24 subfamily A member 1), mutational and transcriptional profile.

  3. changes in circulating biomarkers induced by chemotherapy [ Time Frame: At the end of each cycle (each cycle is 21 days) ]
    Laboratory testing will be used to determine any changes in circulating biomarkers induced by chemotherapy. Biomarkers to be tested include: Stromal content (collagen and hyaluronan), CD31 (cluster of differentiation 31) staining, PD-1(programmed cell death-1) / PDl-1 (protein disulfide isomerase) staining and expression, IHC (Immunohistochemistry) evaluation of key immune cell populations (cytotoxic T Cells, TAMs (tumor-associated macrophages), MDSCs (myeloid-derived suppressor cells), and Tregs (regulatory T cells in cancer)), clonality of intra-tumoral T cells by TSR (tumor stroma ratio) sequencing (a measure of intratumoral response), expression of VDR (vitamin D receptor) regulated inflammatory gene (IL6 (interleukin 6), CXCL1 (chemokine (C-X-C motif) ligand 1), CSF2 (colony stimulating factor 2), CXCLR(chemokine (C-X-C motif) receptor)), VDR and CYP24A1 (cytochrome P450 family 24 subfamily A member 1), mutational and transcriptional profile.

  4. pharmacodynamics effect of Paricalcitol [ Time Frame: At the end of 2 cycles (each cycle is 21 days) ]
    Tumor biopsy testing will be used to determine the pharmacodynamics effect of Paricalcitol for patients with metastatic PDA (pancreatic ductal adenocarcinoma) . Fresh tumor biopsies will be obtained to evaluate the pharmacodynamics effect of Paricalcitol on PDA, a core biopsy will be performed at baseline prior to the addition of paricalcitol along with one after 2 cycles of the triplet regimen plus paricalcitol (6 weeks).

  5. Parathyroid Hormone (PTH) [ Time Frame: At the end of each cycle (each cycle is 21 days) ]
    Laboratory testing will be used to monitor any changes in parathyroid hormone (PTH) in individuals treated with paricalcitol.

  6. Vitamin D 25-hydroxy (OH) [ Time Frame: At the end of each cycle (each cycle is 21 days) ]
    Laboratory testing will be used to monitor and measure the serum levels of Vitamin D 25-OH after each cycle of therapy



Information from the National Library of Medicine

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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; male or female.
  2. Histologically or cytologically confirmed metastatic pancreatic ductal adenocarcinoma.
  3. Capable of providing informed consent and complying with trial procedures including obtaining paired biopsies during therapy
  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 agree not 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 and until 90 days after last dose of study treatment. 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 Fluorouracil (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 or squamous cell carcinoma, superficial bladder cancer, prostate cancer in active surveillance, or carcinoma in situ of the cervix) unless documented free of cancer for ≥2 years.
  6. Laboratory values: Screening serum creatinine >1.5 mg/dL; total bilirubin > (ULN); alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≥ 2.5x 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 anticoagulation agents.
  7. Current, serious, clinically significant cardiac arrhythmias as determined by the investigator.
  8. History of HIV infection.
  9. Active, clinically significant serious infection requiring treatment with antibiotics, antivirals or anti-fungals.
  10. Any condition that might interfere with the patient's participation in the study or in the evaluation of the study results.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03415854


Contacts
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Contact: Brandy Carothers 480-323-1323 brandy.carothers@honorhealth.com
Contact: Andrea Brooks 480-323-1029 andrea.brooks@honorhealth.com

Locations
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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
Barts Cancer Institute
Abramson Cancer Center of the University of Pennsylvania
Salk Institute for Biological Studies
Mayo Clinic
Princeton University
Imaging Endpoints
Translational Genomics Research Institute
Stand Up To Cancer
Cancer Research UK
Lustgarten Foundation
University of California, San Diego
Investigators
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Principal Investigator: Erkut Borazanci, MD HonorHealth Research Institute

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Responsible Party: HonorHealth Research Institute
ClinicalTrials.gov Identifier: NCT03415854     History of Changes
Other Study ID Numbers: SU2C HRI NPG-001
First Posted: January 30, 2018    Key Record Dates
Last Update Posted: August 6, 2019
Last Verified: August 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description:

If the study site is a 'covered site' under the definitions of the Health Insurance Portability and Accounting Act (HIPAA), the Investigator will ensure that the patient consents to the use of data by HonorHealth and its designees for the purposes of regulatory submissions, study publications, and drug approval.

Stand Up To Cancer (SU2C) will be notified of any outputs of the research such as guidelines, publications, presentation, changes in service delivery etc. prior to external submission or presentation. In any oral or written report or poster presentation of Results or otherwise relating to the Research, the support of Cancer Research UK (CRUK), SU2C and the Lustgarten foundation will be acknowledged, displaying the relevant logs where possible. Any publications resulting from research funded in whole or in part by the Grant must be cited as required per signed confidentiality agreements.

Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Clinical Study Report (CSR)
Time Frame: To be determined
Access Criteria:

The Investigator and any other study personnel involved in this study shall not disclose, or use for any purposes (other than for the performance of this study), any data, records, or other information (hereinafter collectively "information") disclosed to the Investigator or other study personnel. Such information shall remain the confidential and proprietary property of HonorHealth, and shall be disclosed only to the Investigator or other designated study personnel.

The obligation of non-disclosure shall not apply to the following:

  • relevant disclosure to potential study participants for the purpose of obtaining informed consent;
  • information after such time that it is or becomes publicly available through no fault of the Investigator or other study personnel; and,
  • information after such time that it is disclosed to the Investigator by a third party entitled to disclose such information.

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes

Additional relevant MeSH terms:
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Adenocarcinoma
Pancreatic Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Ergocalciferols
Gemcitabine
Paclitaxel
Albumin-Bound Paclitaxel
Cisplatin
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