Chemotherapy + Paricalcitol for Pancreatic Cancer

(NABPLAGEMD Trial)

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: HonorHealth Research Institute

Must not be taking: Antibiotics, Antivirals

Disqualifiers: CNS metastasis, Other malignancies, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: 9 weeks

11 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, it does mention that you should not have received any previous treatments for metastatic disease and should not have taken any investigational agents within 4 weeks before starting the study.

What evidence supports the effectiveness of the drug Paricalcitol for treating pancreatic cancer?

Research shows that Paricalcitol, a form of vitamin D, can slow down the growth of pancreatic cancer cells in both lab studies and animal tests. It works by increasing certain proteins that help stop cancer cells from multiplying, and it does this without causing harmful calcium levels in the body. ^{1 2 3 4 5}

Is the combination of chemotherapy and Paricalcitol safe for treating pancreatic cancer?

Paricalcitol, also known as Zemplar, has been shown to be well-tolerated in clinical trials for other conditions, like myelodysplastic syndrome, with minimal side effects. It is a form of vitamin D that has been used safely in humans and is less likely to cause high calcium levels in the blood compared to other vitamin D forms. ^{1 2 3 4 6}

What makes the drug Paricalcitol unique for treating pancreatic cancer?

Paricalcitol is unique because it is a vitamin D analog that inhibits pancreatic cancer cell growth without causing the harmful calcium-related side effects associated with other forms of vitamin D. This makes it a promising option for pancreatic cancer, which has limited effective treatments. ^{1 2 3 4 7}

What is the purpose of this trial?

This trial tests a combination of three chemotherapy drugs and a form of Vitamin D for patients with advanced pancreatic cancer who haven't been treated before. The drugs aim to kill cancer cells and stop their growth, while the Vitamin D helps make the cancer more responsive to treatment. Vitamin D has long been evaluated for benefit as a protective agent and treatment for malignancies, including pancreatic cancer, but there is no clear evidence that supplementation improves outcomes in pancreatic cancer to date.

Research Team

Erkut Borazanci, MD

Principal Investigator

HonorHealth Research Institute

Eligibility Criteria

This trial is for adults with untreated metastatic pancreatic ductal adenocarcinoma. Participants must have a life expectancy of at least 12 weeks, measurable tumor lesions, and be able to consent to the study's procedures including biopsies. Women should not be pregnant or breastfeeding and both genders must practice birth control during the study.

Inclusion Criteria

Karnofsky Performance Status (KPS) of ≥ 70%.

Life expectancy ≥ 12 weeks.

Histologically or cytologically confirmed metastatic pancreatic ductal adenocarcinoma.

Exclusion Criteria

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.

Exposure to any investigational agent within 4 weeks prior to initiation of study treatment.

Evidence of central nervous system (CNS) metastasis (negative imaging study, if clinically indicated, within 4 weeks of Screening Visit).

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive paclitaxel protein bound, gemcitabine, and cisplatin for 3 cycles, each cycle lasting 21 days

9 weeks

3 visits (in-person) for each cycle

Progression Treatment

Upon disease progression, paricalcitol is added to the treatment regimen

Until further disease progression

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Paricalcitol

Trial Overview The trial tests if combining paclitaxel protein bound (a chemotherapy drug), gemcitabine, cisplatin (another chemo drug), and paricalcitol can effectively treat individuals with metastatic pancreatic cancer who haven't had previous treatments for their advanced disease.

Participant Groups

Group I: Paricalcitol (Zemplar) Experimental Treatment 1 Intervention

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.

Paricalcitol is already approved in United States, European Union for the following indications:

Approved in United States as Zemplar for:

• Secondary hyperparathyroidism associated with chronic kidney disease

Approved in European Union as Paricalcitol for:

• Secondary hyperparathyroidism associated with chronic kidney disease

Who Is Running the Clinical Trial?

HonorHealth Research Institute

Lead Sponsor

Trials

26

Recruited

940+

Imaging Endpoints

Collaborator

Trials

3

Recruited

290+

Abramson Cancer Center at Penn Medicine

Collaborator

Trials

425

Recruited

464,000+

Mayo Clinic

Collaborator

Trials

3,427

Recruited

3,221,000+

Stand Up To Cancer

Collaborator

Trials

53

Recruited

40,100+

Abramson Cancer Center of the University of Pennsylvania

Collaborator

Trials

360

Recruited

108,000+

Princeton University

Collaborator

Trials

7

Recruited

4,400+

Lustgarten Foundation

Collaborator

Trials

27

Recruited

5,500+

Cancer Research UK

Collaborator

Trials

262

Recruited

4,435,000+

University of California, San Diego

Collaborator

Trials

1,215

Recruited

1,593,000+

Findings from Research

The new vitamin D3 analogue, 22-oxa-calcitriol, showed significantly greater anti-proliferative effects on pancreatic cancer cell lines compared to calcitriol, particularly in inhibiting the growth of BxPC-3 xenografts in mice without causing hypercalcemia.

Both 22-oxa-calcitriol and calcitriol caused cell cycle arrest in some pancreatic cancer cell lines, but the effectiveness of these treatments was not solely determined by the levels or mutations of the vitamin D receptor, indicating other factors may influence their efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inhibitory effect of 220-oxa-1,25-dihydroxyvitamin D3 on the proliferation of pancreatic cancer cell lines. Kawa, S., Yoshizawa, K., Tokoo, M., et al.[2019]

In a phase II study involving 25 patients with non-resectable pancreatic cancer, the combination of high-dose oral calcitriol and docetaxel showed some efficacy, with 12% of patients achieving a partial response and 28% having stable disease.

The median time-to-progression was 15 weeks and overall survival was 24 weeks, indicating that while this treatment may offer some benefits, it does not appear to be more effective than existing treatments like gemcitabine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of calcitriol-enhanced docetaxel in patients with previously untreated metastatic or locally advanced pancreatic cancer. Blanke, CD., Beer, TM., Todd, K., et al.[2018]

Paricalcitol, a less calcemic analog of calcitriol, effectively inhibits the growth of pancreatic tumor cell lines in vitro and in vivo, similar to the effects of 1,25(OH)(2)D(3).

In a study involving pancreatic tumor cell xenografts in mice, paricalcitol demonstrated tumor growth inhibition without causing hypercalcemia, suggesting it could be a safer therapeutic option for pancreatic cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

19-nor-1 alpha,25-dihydroxyvitamin D2 (paricalcitol) inhibits the proliferation of human pancreatic cancer cells in vitro and in vivo. Schwartz, GG., Eads, D., Naczki, C., et al.[2020]

In a clinical trial involving 12 patients with myelodysplastic syndrome (MDS), paricalcitol was well-tolerated, showing minimal side effects, but did not meet efficacy criteria for treatment as a single agent.

While one patient experienced a notable increase in platelet count, the overall results suggest that paricalcitol alone is not effective for MDS, indicating the need for further research into its use in combination with other therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vitamin D(2) analog (Paricalcitol; Zemplar) for treatment of myelodysplastic syndrome. Koeffler, HP., Aslanian, N., O'Kelly, J.[2014]

References

1. United States pubmed.ncbi.nlm.nih.gov

Inhibitory effect of 220-oxa-1,25-dihydroxyvitamin D3 on the proliferation of pancreatic cancer cell lines. [2019]

2. United States pubmed.ncbi.nlm.nih.gov

Phase II study of calcitriol-enhanced docetaxel in patients with previously untreated metastatic or locally advanced pancreatic cancer. [2018]

3. United States pubmed.ncbi.nlm.nih.gov

Vitamin D for the prevention and treatment of pancreatic cancer. [2021]

4. United States pubmed.ncbi.nlm.nih.gov

19-nor-1 alpha,25-dihydroxyvitamin D2 (paricalcitol) inhibits the proliferation of human pancreatic cancer cells in vitro and in vivo. [2020]

5. Ireland pubmed.ncbi.nlm.nih.gov

Vitamin D and pancreatic cancer. [2018]

6. England pubmed.ncbi.nlm.nih.gov

Vitamin D(2) analog (Paricalcitol; Zemplar) for treatment of myelodysplastic syndrome. [2014]

7. United States pubmed.ncbi.nlm.nih.gov

Prediagnostic Plasma 25-Hydroxyvitamin D and Pancreatic Cancer Survival. [2021]