NCT05365893

PHL Treatment in Pancreatic Cancer

Window of Opportunity for Neoadjuvant Stroma Modification in Pancreatic Cancer

• Status: Recruiting
• Phase: EARLY_Phase 1
• Study type: Interventional
• Enrollment: 20 (estimated)
• Sponsor: Fox Chase Cancer Center · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This proposal will investigate the effect of paricalcitol, hydroxychloroquine, and losartan (PHL) combination of 3 stroma-modifying drugs on pancreatic adenocarcinoma and its stroma.

Detailed description

This study will test the feasibility and safety of these pancreatic ductal adenocarcinoma (PDAC) stroma modulators in the pre-operative setting, and will offer the opportunity to detect the combined effect on PDAC tissue constituents to validate the mechanism using real-time biologic end points. The long-term goal for PHL is to deploy this regimen in combination with chemotherapy to treat PDAC. Further, this study will establish a paradigm of a "window" trial (the use of novel therapies in the period of time between the end of neoadjuvant treatment and surgery) to test new compounds and establish their biological activities in PDAC. This pilot trial will establish the feasibility and determine the biological activity of PHL combination given prior to surgery to 10 patients who completed neoadjuvant therapy (NAT) with modified FOLFIRINOX and chemoradiation using sequential blood and tissue samples (blood samples will be collected pre NAT and post chemotherapy; post chemoradiation; pre-surgery and post-surgery) and compare with 10 patients who undergo the same neoadjuvant therapy (modified FOLFIRINOX followed by chemo-RT and proceed to surgery without treatment with PHL regimen (blood sample in this group will be collected pre NAT and post-chemotherapy; post-chemoradiation, pre-surgery and post-surgery). This is a single site pilot study of PHL in patients with resectable non-metastatic PDAC. Study will enroll 20 patients who will be consented prior to initiation of NAT to donate blood (pre NAT, post neoadjuvant chemotherapy and post neoadjuvant radiation and pre and post-surgery) and tissue (archival tissue from diagnosis biopsy and surgical specimen). All patients will complete a minimum of 3 months of modified FOLFIRINOX + chemoradiation. Of these 20 patients, 10 will receive the study PHL regimen (Arm A) and 10 will serve as the control arm (Arm B). 10 patients will be treated with resectable non-metastatic PDAC with a combination of three stroma-modifying agents PHL during the "window of opportunity", spanning 4-8 weeks after conclusion of neoadjuvant chemotherapy plus radiation and prior to surgery (Fig 1). Neoadjuvant chemotherapy will consist of at least 3 months of modified FOLFIRINOX regimen followed by chemoradiotherapy. The choice of chemotherapy given concurrently with radiation will be at the discretion of the medical team and the patient. Patients should start on the trial medications at least 4 weeks prior to surgery and continue to take the medication until the day before surgery. All the patients in the treatment arm must receive PHL for a minimum of 4 weeks and for a maximum period of 8 weeks. Patients who discontinue before completing 4 weeks of therapy due to disease progression may be replaced.

Conditions

• Pancreatic Ductal Adenocarcinoma

Interventions

Type	Name	Description
COMBINATION_PRODUCT	Paricalcitol, Hydroxychloroquine, Losartan	Paricalcitol 25 mcg IV administered M-W-F Hydroxychloroquine 600 mg PO BID Losartan 50 mg PO daily
OTHER	Neoadjuvant therapy and surgery only (Control)	Control arm These patients will proceed to surgery at completion of neoadjuvant therapy.

Timeline

• Start date: 2021-10-20
• Primary completion: 2026-03-31
• Completion: 2026-12-31
• First posted: 2022-05-09
• Last updated: 2025-04-16

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study