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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether a combination of chemotherapy drugs and paricalcitol (a form of vitamin D) can effectively treat individuals with previously untreated metastatic pancreatic cancer. Participants will undergo a series of treatments over three cycles, followed by tests to assess the cancer's response. Those diagnosed with metastatic pancreatic ductal adenocarcinoma who have not yet received treatment may be suitable for this study. As a Phase 2 trial, the research focuses on evaluating the treatment's effectiveness in an initial, smaller group of participants.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that paricalcitol is generally safe for people. One study used paricalcitol with another drug and administered it to patients. Even at higher doses, it did not cause serious side effects like elevated calcium levels in the blood. Another study with 12 patients found that paricalcitol caused only minor side effects.

In a different study with 44 patients, the main side effect at higher doses was excessive sleepiness. Overall, these findings suggest that paricalcitol is safe and causes few problems for most people. However, as with any treatment, side effects can occur, so discussing any concerns with a doctor is important. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for pancreatic cancer?

Researchers are excited about paricalcitol for pancreatic cancer because it offers a novel approach compared to current treatments. Unlike traditional chemotherapy that targets rapidly dividing cells, paricalcitol is a synthetic form of vitamin D2 that may help regulate immune response and inhibit cancer cell growth. This unique mechanism of action could enhance the effectiveness of chemotherapy and potentially improve patient outcomes by targeting the cancer more precisely. Moreover, paricalcitol's potential to normalize CA19-9, a marker used to evaluate pancreatic cancer progression, could provide a more immediate assessment of treatment efficacy.

What evidence suggests that this treatment might be an effective treatment for pancreatic cancer?

Studies have shown that paricalcitol may slow the growth of pancreatic cancer cells. In lab tests and animal studies, paricalcitol stopped pancreatic tumors from growing. Research suggests that paricalcitol reduces cancer cell activity, potentially enhancing the effects of chemotherapy drugs. Although information from human studies remains limited, these early findings indicate that paricalcitol might improve the effectiveness of standard chemotherapy treatments for pancreatic cancer. Participants in this trial will receive paricalcitol as part of the study regimen to evaluate its potential benefits in combination with chemotherapy. ^{1 2 5 6 7}

Who Is on the Research Team?

Erkut Borazanci, MD

Principal Investigator

HonorHealth Research Institute

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11009835/

A phase 1 open label, dose escalation study of intravenous ... Paricalcitol can be safely administered in doses up to 7 mcg/kg weekly with fixed-dose rate gemcitabine without dose-limiting hypercalcemia.

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/18094617/

19-nor-1 alpha,25-dihydroxyvitamin D2 (paricalcitol ... Paricalcitol, given three times per week inhibited the growth of AsPC-1 pancreatic tumor cell xenografts in nude mice at a dose that did not cause ...

3. acsjournals.onlinelibrary.wiley.com acsjournals.onlinelibrary.wiley.com/doi/full/10.1002/cncr.31676

A phase 1, open‐label, dose escalation study of intravenous ... A total of 44 patients were enrolled. Somnolence was the main dose-limiting toxicity. The highest dose of paricalcitol administered was 10.5 µg/ ...

4. cell.com cell.com/cell-reports-medicine/fulltext/S2666-3791(24)00652-9

Mechanism of enhancing chemotherapy efficacy in ... 19-nor-1α, 25-Dihydroxyvitamin D2 (Paricalcitol) inhibits the proliferation of human pancreatic cancer cells in vitro and in vivo. Cancer Biol. Ther. 2008; 7 ...

5. aacrjournals.org aacrjournals.org/cancerpreventionresearch/article/9/6/491/50544/Paricalcitol-Enhances-the-Chemopreventive-Efficacy

Paricalcitol Enhances the Chemopreventive Efficacy of 5 ... Paricalcitol has also demonstrated potential suppressive effects on a variety of human cancer cells and preclinical tumor models such as pancreatic cancer (14) ...

6. withpower.com withpower.com/trial/phase-3-adenocarcinoma-2018-c2e45

Chemotherapy + Paricalcitol for Pancreatic Cancer In a clinical trial involving 12 patients with myelodysplastic syndrome (MDS), paricalcitol was well-tolerated, showing minimal side effects, but did not meet ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S2405844024176293

The therapeutic potential of vitamins A, C, and D in ... While this study found good tolerability of the compound, no antitumor efficacy was recorded. In a phase II clinical trial, the efficacy of a ...