Paricalcitol Plus Gemcitabine and Nab-paclitaxel in Metastatic Pancreatic Cancer

NCT03520790 | Terminated Phase 1 DMC FDA Drug

• 1 other identifier: 18-021
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 2

Brief Summary

This research study is a two stage study which consists of a safety run-in phase and a randomized phase 2 study which include subjects with previously-untreated, metastatic pancreatic adenocarcinoma. In the run-in safety study, the safety of adding two formulations (IV or Oral) of paricalcitol to a standard chemotherapy program of gemcitabine and nab-paclitaxel will be evaluated. The randomized phase 2 study will evaluate the efficacy of paricalcitol when added to gemcitabine and nab-paclitaxel The drugs involved in this study are:

• Paricalcitol
• Gemcitabine
• Nab-paclitaxel

Conditions

Pancreatic Cancer

Keywords

Pancreatic Cancer

Outcome Measures

Primary Outcomes (2)

• Assess adverse events (per CTCAE v4.0 criteria)

  Assess the adverse events (per CTCAE v4.0 criteria) associated with the addition of paricalcitol to gemcitabine and nab-paclitaxel in phase I participants.

  2 years

• Overall survival

  Evaluate overall survival (OS) in patients with metastatic pancreatic cancer receiving gemcitabine and nab-paclitaxel with or without paricalcitol in phase I/II participants.

  2 Years

Secondary Outcomes (3)

• Assess adverse events (per CTCAE v4.0 criteria)

  2 years

• Response rate

  2 years

• Progression free survival

  2 years

Study Arms (3)

Gemcitabine + Nab-paclitaxel + Placebo

EXPERIMENTAL

* Gemcitabine and Nab-paclitaxel is administered intravenously 3 times/cycle. * Placebo is administered orally on a daily basis

Drug: Gemcitabine; Drug: Nab-paclitaxel; Other: Placebo

Gemcitabine + Nab-paclitaxel + Paricalcitol IV

EXPERIMENTAL

* Gemcitabine + Nab-paclitaxel is administered intravenously 3 times/cycle. * Paricalcitol is administered intravenously once weekly.

Drug: Gemcitabine; Drug: Nab-paclitaxel; Drug: Paricalcitol

Gemcitabine + Nab-paclitaxel + Paricalcitol oral

EXPERIMENTAL

* Gemcitabine + Nab-paclitaxel is administered intravenously 3 times/cycle. * Paricalcitol is administered orally on a daily basis

Drug: Gemcitabine; Drug: Nab-paclitaxel; Drug: Paricalcitol

Interventions

Gemcitabine DRUG

Gemcitabine is a chemotherapy agent. Chemotherapy agents are medicines that kill cancer cells.

Also known as: Gemzar

Gemcitabine + Nab-paclitaxel + Paricalcitol IV; Gemcitabine + Nab-paclitaxel + Paricalcitol oral; Gemcitabine + Nab-paclitaxel + Placebo

Nab-paclitaxel DRUG

Nab-paclitaxel is a chemotherapy agent. Chemotherapy agents are medicines that kill cancer cells.

Also known as: Abraxane

Gemcitabine + Nab-paclitaxel + Paricalcitol IV; Gemcitabine + Nab-paclitaxel + Paricalcitol oral; Gemcitabine + Nab-paclitaxel + Placebo

Paricalcitol DRUG

Paricalcitol (IV or oral) is a man-made form of vitamin D. It is thought to work by blocking a signal in the cancer tumor cells that leads to growth and spreading of the tumor.

Gemcitabine + Nab-paclitaxel + Paricalcitol IV; Gemcitabine + Nab-paclitaxel + Paricalcitol oral

Placebo OTHER

Placebo

Gemcitabine + Nab-paclitaxel + Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically-confirmed pancreatic adenocarcinoma or poorly differentiated carcinoma that is metastatic to distant sites.
• Other histologies such as neuroendocrine and acinar cell carcinoma are excluded. Patients with locally advanced, unresectable disease without distant metastases are excluded.
• No prior chemotherapy for locally advanced or metastatic pancreatic cancer.
• Patients are eligible if they received adjuvant treatment after surgical resection with single-agent gemcitabine or gemcitabine plus capecitabine or gemcitabine and nab-paclitaxel or 5-fluorouracil/leucovorin or 5-FU/leucovorin plus irinotecan and oxaliplatin that was completed \>12 months before enrollment. Similarly, adjuvant radiation +/- chemosensitization with 5-fluorouracil, capecitabine, or gemcitabine is allowed if completed \>12 months before enrollment.
• Participants must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as ≥20 mm with conventional techniques or as ≥10 mm with spiral CT scan, MRI, or calipers by clinical exam. See Section 11 for the evaluation of measurable disease.
• Age greater than or equal to 18 years.
• Patients must have completed any major surgery or open biopsy ≥4 weeks from start of treatment.
• ECOG performance status ≤1 (see Appendix A)
• Participants must have normal organ and marrow function as defined below:
• Absolute neutrophil count ≥1,500/mcL
• Platelets ≥100,000/mcL
• Total bilirubin ≤1.5 × institutional upper limit of normal
• AST(SGOT)/ALT(SGPT) ≤2.5 × institutional upper limit of normal
• Calcium (corrected for albumin) \* ≤1 × institutional upper limit of normal
• Creatinine ≤1.5 × institutional upper limit of normal OR

You may not qualify if:

• Prior chemotherapy or any other investigational agents for the treatment of locally advanced or metastatic pancreatic cancer
• Concurrent use of any other anti-cancer therapy, including chemotherapy, targeted therapy, immunotherapy, or biological agents.
• Participants with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to paricalcitol, gemcitabine or nab-paclitaxel
• Pre-existing hypercalcemia, defined as baseline serum calcium (corrected for albumin) above the institutional upper limit of normal.
• At the time of trial enrollment, vitamin D containing supplements must be stopped and no vitamin D supplements can be taken while the patient is enrolled to the study due to increased risk for hypercalcemia
• At the time of trial enrollment, calcium containing supplements must be stopped and no calcium supplements can be taken while the patient is enrolled to the study due to increased risk for hypercalcemia
• History of symptomatic genitourinary stones (e.g. kidney stones) within the past 12 months
• History of prior or current synchronous malignancy, except:
• Malignancy that was treated with curative intent and for which there has been no known active disease for \>3 years prior to enrollment
• Curatively treated non-melanoma skin cancer, cervical cancer in situ, or prostatic intraepithelial neoplasia, without evidence of prostate cancer
• Pre-existing, clinically significant peripheral neuropathy, defined as CTCAE grade 2 or higher neurosensory or neuromotor toxicity, regardless of etiology
• Regular use of thiazide diuretics (e.g. hydrochlorothiazide), which can lead to hypercalcemia. Patients must stop these diuretics prior to initiating treatment. Other anti-hypertensive medications can be substituted, as needed.
• Participants receiving any medications or substances that are inhibitors or inducers of CYP450 3A enzyme(s) are ineligible. Because the lists of these agents are constantly changing, it is important to regularly consult a frequently-updated list such as http://medicine.iupui.edu/clinpharm/ddis/table.aspx; medical reference texts such as the Physicians' Desk Reference may also provide this information. As part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product. \[see Appendix D\]
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead
• Stand Up To Cancer: collaborator
• Lustgarten Foundation: collaborator
• American Association for Cancer Research: collaborator

Study Sites (2)

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Penn Medicine

Philadelphia, Pennsylvania, 19104, United States

Location

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

Gemcitabine; 130-nm albumin-bound paclitaxel; Albumin-Bound Paclitaxel; paricalcitol

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Paclitaxel; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Albumins; Proteins; Amino Acids, Peptides, and Proteins

Study Officials

• Kimberly Perez, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: April 18, 2018
• First Posted: May 11, 2018
• Study Start: December 5, 2018
• Primary Completion: July 1, 2024
• Study Completion: July 1, 2024
• Last Updated: March 21, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)