Vitamin D Receptor Agonist Paricalcitol Plus Gemcitabine and Nab-paclitaxel in Patients With Metastatic Pancreatic Cancer
Overview
- Phase
- Phase 1
- Intervention
- Gemcitabine
- Conditions
- Pancreatic Cancer
- Sponsor
- Dana-Farber Cancer Institute
- Enrollment
- 36
- Locations
- 2
- Primary Endpoint
- Overall survival
- Status
- Terminated
- Last Updated
- last year
Overview
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
Detailed Description
Pancreatic cancer is an aggressive disease with treatment options associated with modest benefit, therefore, new treatment options are needed. Paricalcitol 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. Paricalcitol was approved by the Food and Drug Administration (FDA) for the prevention and treatment of elevated calcium levels associated with chronic renal failure. The FDA has not approved paricalcitol as a treatment for pancreatic cancer. This research study is being performed to evaluate the benefit of paricalcitol in combination with gemcitabine and nab-paclitaxel for this disease. The FDA (the U.S. Food and Drug Administration) has approved the combination of gemcitabine and nab-paclitaxel as a treatment option for this disease. Treatment will consists of 4 week treatment cycles. Paricalcitol in the oral formulation will be taken daily, in the intravenous formulation will be administered three times a week. Nab-paclitaxel and gemcitabine will be administered on days 1,8, and 15. Subjects continue in the study until disease progression, adverse event/toxicity, death or either the subject or sponsor discontinues the study. In this research study, the main objectives include: * Assess adverse side effects associated with the combination of paricalcitol with gemcitabine and nab-paclitaxel. * Evaluate overall survival in patients with pancreatic cancer receiving gemcitabine and nab-paclitaxel with or without paricalcitol. Phase II was not pursued due to futility based on the results of the NAPOLI-3 therapeutic clinical trial.
Investigators
Kimberly Perez, MD
Principal Investigator
Dana-Farber Cancer Institute
Eligibility Criteria
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 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
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
Arms & Interventions
Gemcitabine + Nab-paclitaxel + Placebo
* Gemcitabine and Nab-paclitaxel is administered intravenously 3 times/cycle. * Placebo is administered orally on a daily basis
Intervention: Gemcitabine
Gemcitabine + Nab-paclitaxel + Placebo
* Gemcitabine and Nab-paclitaxel is administered intravenously 3 times/cycle. * Placebo is administered orally on a daily basis
Intervention: Nab-paclitaxel
Gemcitabine + Nab-paclitaxel + Placebo
* Gemcitabine and Nab-paclitaxel is administered intravenously 3 times/cycle. * Placebo is administered orally on a daily basis
Intervention: Placebo
Gemcitabine + Nab-paclitaxel + Paricalcitol IV
* Gemcitabine + Nab-paclitaxel is administered intravenously 3 times/cycle. * Paricalcitol is administered intravenously once weekly.
Intervention: Gemcitabine
Gemcitabine + Nab-paclitaxel + Paricalcitol IV
* Gemcitabine + Nab-paclitaxel is administered intravenously 3 times/cycle. * Paricalcitol is administered intravenously once weekly.
Intervention: Nab-paclitaxel
Gemcitabine + Nab-paclitaxel + Paricalcitol IV
* Gemcitabine + Nab-paclitaxel is administered intravenously 3 times/cycle. * Paricalcitol is administered intravenously once weekly.
Intervention: Paricalcitol
Gemcitabine + Nab-paclitaxel + Paricalcitol oral
* Gemcitabine + Nab-paclitaxel is administered intravenously 3 times/cycle. * Paricalcitol is administered orally on a daily basis
Intervention: Gemcitabine
Gemcitabine + Nab-paclitaxel + Paricalcitol oral
* Gemcitabine + Nab-paclitaxel is administered intravenously 3 times/cycle. * Paricalcitol is administered orally on a daily basis
Intervention: Nab-paclitaxel
Gemcitabine + Nab-paclitaxel + Paricalcitol oral
* Gemcitabine + Nab-paclitaxel is administered intravenously 3 times/cycle. * Paricalcitol is administered orally on a daily basis
Intervention: Paricalcitol
Outcomes
Primary Outcomes
Overall survival
Time Frame: 2 Years
Evaluate overall survival (OS) in patients with metastatic pancreatic cancer receiving gemcitabine and nab-paclitaxel with or without paricalcitol in phase I/II participants.
Assess adverse events (per CTCAE v4.0 criteria)
Time Frame: 2 years
Assess the adverse events (per CTCAE v4.0 criteria) associated with the addition of paricalcitol to gemcitabine and nab-paclitaxel in phase I participants.
Secondary Outcomes
- Assess adverse events (per CTCAE v4.0 criteria)(2 years)
- Response rate(2 years)
- Progression free survival(2 years)