Skip to main content

Paricalcitol, Gemcitabine Hydrochloride, and Nab-Paclitaxel in Treating Patients with Metastatic Pancreatic Cancer

Trial Status: Active

This phase I / II trial studies the side effects and how well paricalcitol, gemcitabine hydrochloride, and nab-paclitaxel work in treating patients with pancreatic cancer that has spread to other places in the body (metastatic). Paricalcitol is a form of vitamin D that works by blocking a signal in the cancer tumor cells that leads to growth and spreading of the tumor. Drugs used in chemotherapy, such as gemcitabine hydrochloride and nab-paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving paricalcitol, gemcitabine hydrochloride, and nab-paclitaxel may work better in treating patients with metastatic pancreatic cancer.

Inclusion Criteria

  • 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 5-fluorouracil/leucovorin 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 computed tomography (CT) scan, magnetic resonance imaging (MRI), or calipers by clinical exam
  • Patients must have completed any major surgery or open biopsy >= 4 weeks from start of treatment
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 1
  • Absolute neutrophil count >= 1,500/mcL
  • Platelets >= 100,000/mcL
  • Total bilirubin =< 1.5 x institutional upper limit of normal
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional upper limit of normal
  • Calcium (corrected for albumin) * =< 1 x institutional upper limit of normal * Corrected calcium = serum calcium (mg/dL) + 0.8 (4 – serum albumin [g/dL])
  • Creatinine =< 1.5 x institutional upper limit of normal OR creatinine clearance >= 60 mL/min/1.73 m^2 for participants with creatinine levels above 1.5 x upper limit of normal
  • Ability to understand and the willingness to sign a written informed consent document
  • Negative pregnancy testing for women of child bearing age
  • The effects of paricalcitol, gemcitabine and nab-paclitaxel on the developing human fetus are unknown. For this reason and because vitamin D receptor agonist agents as well as other therapeutic agents used in this trial are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of treatment administration

Exclusion Criteria

  • 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
  • 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
  • Participant must be able to swallow and absorb pills
  • Pregnant women are excluded from this study because paricalcitol is a vitamin D receptor agonist agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with paricalcitol, breastfeeding should be discontinued if the mother is treated with paricalcitol. These potential risks may also apply to other agents used in this study

Massachusetts

Boston
Brigham and Women's Hospital
Status: ACTIVE
Contact: Kimberly J. Perez
Dana-Farber Cancer Institute
Status: ACTIVE
Contact: Kimberly J. Perez
Milford
Dana-Farber / Brigham and Women's Cancer Center at Milford Regional
Status: ACTIVE
Contact: Michael Constantine
South Weymouth
Dana-Farber / Brigham and Women's Cancer Center at South Shore
Status: ACTIVE
Contact: Jingjing Hu

PRIMARY OBJECTIVES:

I. To assess adverse events (per Common Terminology Criteria for Adverse Events [CTCAE] version [v]4.0 criteria) associated with addition of paricalcitol to gemcitabine and nab-paclitaxel. (Safety run-in)

II. To evaluate overall survival (OS) in patients with metastatic pancreatic cancer receiving gemcitabine and nab-paclitaxel with or without paricalcitol. (Phase II)

SECONDARY OBJECTIVE:

I. To evaluate safety, response rate (RR) and progression-free survival (PFS) in patients with metastatic pancreatic cancer receiving gemcitabine and nab-paclitaxel with or without paricalcitol. (Phase II)

EXPLORATORY OBJECTIVES:

I. Pharmacodynamic assessment of VDR binding by the oral and intravenous paricalcitol preparations when given concurrently with gemcitabine and nab-paclitaxel. (Safety run-in)

II. To explore a tumor-derived predictive biomarker for treatment efficacy with gemcitabine, nab-paclitaxel, and paricalcitol. (Phase II)

OUTLINE:

SAFETY RUN-IN PHASE: Patients are randomized to 1 of 3 arms.

ARM A: Patients receive nab-paclitaxel intravenously (IV) over 30 minutes and gemcitabine hydrochloride IV over 30 minutes on days 1, 8, and 15. Patients also receive a placebo orally (PO) once daily (QD) on days 1-28. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.

ARM B: Patients receive nab-paclitaxel IV over 30 minutes and gemcitabine hydrochloride IV over 30 minutes on days 1, 8, and 15. Patients also receive paricalcitol IV once weekly (QW). Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.

ARM C: Patients receive nab-paclitaxel IV over 30 minutes and gemcitabine hydrochloride IV over 30 minutes on days 1, 8, and 15. Patients also receive paricalcitol PO QD on days 1-28. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.

PHASE II: Patient are randomized to 1 of 2 arms.

ARM D: Patients receive nab-paclitaxel IV over 30 minutes and gemcitabine hydrochloride IV over 30 minutes on days 1, 8, and 15. Patients also receive a placebo PO QD on days 1-28 or IV QW. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.

ARM E: Patients receive nab-paclitaxel IV over 30 minutes and gemcitabine hydrochloride IV over 30 minutes on days 1, 8, and 15. Patients also receive paricalcitol PO QD on days 1-28 or IV QW. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 52 weeks.

Trial Phase Phase I/II

Trial Type Treatment

Lead Organization
Dana-Farber Harvard Cancer Center

Principal Investigator
Kimberly J. Perez

  • Primary ID 18-021
  • Secondary IDs NCI-2018-03520
  • Clinicaltrials.gov ID NCT03520790