Liposomal Irinotecan Plus 5-FU / LV Combined With Paricalcitol in Patients With Advanced Pancreatic Cancer Progressed on Gemcitabine-based Therapy

NCT03883919 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: 201905201
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

Given the efficacy of nanoliposomal irinotecan as a second-line regimen in pancreatic ductal adenocarcinoma (PDAC), together with the favorable toxicity profile of paricalcitol and its interplay with irinotecan metabolism, the investigators propose a second-line pilot study in advanced PDAC that will enroll patients who have progressed on a gemcitabine-based regimen.

Conditions

Pancreatic Cancer; Pancreas Cancer; Cancer of the Pancreas

Outcome Measures

Primary Outcomes (1)

• Tolerability between two different dose levels of paricalcitol added to the combo regimen of liposomal irinotecan plus 5-FU / LV as measured by the occurrence of grade 3 and 4 toxicities

  -Toxicity will be graded using CTCAE version 5.0

  Through 30 days after completion of paricalcitol treatment (estimated to be 28 weeks)

Secondary Outcomes (7)

• Overall response rate (ORR)

  Through completion of treatment (estimated to be 20 weeks)

• Progression-free survival (PFS)

  Through completion of follow-up (estimated to be 72 weeks)

• Overall survival (OS)

  Through completion of follow-up (estimated to be 72 weeks)

• CA19-9 biochemical response rate

  Through beginning of cycle 10 (estimated to be 18 weeks)

• Duration of overall response

  Through completion of treatment (estimated to be 20 weeks)

Study Arms (2)

Group 1: Paricalcitol 75 mcg Days 1 and 8

EXPERIMENTAL

* 5-FU, LV, and nal-IRI will be administered at standard fixed doses. Briefly, 5-FU will be given at a dose of 2400 mg/m\^2 continuous IV infusion over 46 hours, LV will be given at 400 mg/m\^2 IV over 30 minutes, and liposomal irinotecan will be given at a dose of 70 mg/m\^2 IV over 90 minutes (unless homozygous for the UGT1A1\*28 7/7 allele, in which case the dose will start at 50 mg/m\^2 and escalate to 70 mg/m\^2 in subsequent cycles if no excessive toxicity is experienced) on Day 1 of each 14-day cycle. * Paricalcitol 75 mcg on Days 1 and 8 * Treatment with liposomal irinotecan plus 5FU/ LV may continue indefinitely, and treatment with paricalcitol may continue for up to 10 cycles (20 weeks)

Drug: 5-FU; Drug: Leucovorin; Drug: Liposomal Irinotecan; Drug: Paricalcitol; Procedure: Serum and plasma blood samples; Procedure: Tumor biopsy

Group 2: Paricalcitol 7 mcg/kg Days 1 and 8

EXPERIMENTAL

* 5-FU, LV, and nal-IRI will be administered at standard fixed doses. Briefly, 5-FU will be given at a dose of 2400 mg/m\^2 continuous IV infusion over 46 hours, LV will be given at 400 mg/m\^2 IV over 30 minutes, and liposomal irinotecan will be given at a dose of 70 mg/m\^2 IV over 90 minutes (unless homozygous for the UGT1A1\*28 7/7 allele, in which case the dose will start at 50 mg/m\^2 and escalate to 70 mg/m\^2 in subsequent cycles if no excessive toxicity is experienced) on Day 1 of each 14-day cycle. * Paricalcitol 7 mcg/kg on Days 1 and 8 * Treatment with liposomal irinotecan plus 5FU/ LV may continue indefinitely, and treatment with paricalcitol may continue for up to 10 cycles (20 weeks)

Drug: 5-FU; Drug: Leucovorin; Drug: Liposomal Irinotecan; Drug: Paricalcitol; Procedure: Serum and plasma blood samples; Procedure: Tumor biopsy

Interventions

5-FU DRUG

-Standard of care drug

Also known as: Fluorouracil, Adrucil

Group 1: Paricalcitol 75 mcg Days 1 and 8; Group 2: Paricalcitol 7 mcg/kg Days 1 and 8

Leucovorin DRUG

-Standard of care drug

Also known as: Wellcovorin, Folinic acid

Group 1: Paricalcitol 75 mcg Days 1 and 8; Group 2: Paricalcitol 7 mcg/kg Days 1 and 8

Liposomal Irinotecan DRUG

-Standard of care drug

Also known as: nal-IRI, Onivyde

Group 1: Paricalcitol 75 mcg Days 1 and 8; Group 2: Paricalcitol 7 mcg/kg Days 1 and 8

Paricalcitol DRUG

-Investigational drug

Also known as: Zemplar, Vitamin D

Group 1: Paricalcitol 75 mcg Days 1 and 8; Group 2: Paricalcitol 7 mcg/kg Days 1 and 8

Serum and plasma blood samples PROCEDURE

-baseline, day 1 of each cycle beginning with cycle 2

Group 1: Paricalcitol 75 mcg Days 1 and 8; Group 2: Paricalcitol 7 mcg/kg Days 1 and 8

Tumor biopsy PROCEDURE

* 5 patients in each arm will be required to undergo a mandatory tumor biopsy from the primary pancreatic site or metastatic site, if safe and feasible, prior to cycle 1 * After Cycle 3 of treatment, all patients who had a baseline biopsy will be required to undergo a mandatory biopsy of the same site if safe and feasible.

Group 1: Paricalcitol 75 mcg Days 1 and 8; Group 2: Paricalcitol 7 mcg/kg Days 1 and 8

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically or cytologically confirmed pancreatic adenocarcinoma.
• Must have progressed on or become intolerant to gemcitabine-containing therapy in the advanced setting (not resectable). This is intended to be a second-line trial.
• Measurable disease defined as lesions that can be accurately measured in at least one dimension (longest diameter to be recorded) as ≥ 10 mm with CT scan, as ≥ 20 mm by chest x-ray, or ≥ 10 mm with calipers by clinical exam.
• At least 18 years of age.
• Life expectancy \> 3 months.
• ECOG performance status ≤ 1
• Normal bone marrow and organ function as defined below:
• Absolute neutrophil count ≥ 1,500/mcL
• Platelets ≥ 100,000/mcL
• Hemoglobin ≥ 9 g/dL
• Total bilirubin ≤ 1.5 x ULN
• Serum albumin \> 3g/dL
• AST(SGOT)/ALT(SGPT) ≤ 2.5 x IULN unless there are liver metastases, in which case AST and ALT ≤ 5.0 x IULN
• Creatinine ≤ 1.5 x IULN OR GFR \> 50 mL/min
• Corrected calcium \< 10.3 mg/dL

You may not qualify if:

• More than one prior systemic treatment in the advanced setting. Disease recurrence within 6 months of adjuvant therapy is considered one line of systemic treatment.
• Patients with active renal, ureteral, or bladder stones on the screening imaging.
• Current use of or anticipated need for alternative, holistic, naturopathic, or botanical formulations used for the purpose of cancer treatment.
• A history of other malignancy within 2 years previous, with the exception of those basal cell or squamous cell carcinoma of the skin which were treated with local resection only, or carcinoma in situ of the cervix.
• Currently receiving any other investigational agents.
• Patients who received FOLFIRINOX or FOLFIRI in the neoadjuvant or adjuvant setting who experienced disease recurrence within 6 months will be excluded (patients who received 5-FU or capecitabine as a radiosensitizer are permitted to enroll.)
• Patients with known active/ progressive brain metastases or leptomeningeal involvement will be excluded due to their poor prognosis. Patients with treated/stable brain metastases, defined as patients who have received prior therapy for their brain metastases and whose CNS disease is radiographically stable at study entry, are eligible.
• A history of allergic reactions attributed to compounds of similar chemical or biologic composition to paricalcitol, liposomal irinotecan, 5-FU, LV, or other agents used in the study.
• Clinically significant ascites that requires therapeutic paracentesis or significant pleural effusion that requires therapeutic thoracentesis.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia.
• Pregnant and/or breastfeeding. Women of childbearing potential must have a negative pregnancy test within 7 days of study entry.
• Known HIV-positivity not on anti-retroviral therapy, or with CD4+ T cell count \< 200/ul (patients with known HIV currently on anti-retroviral therapy with CD4+ T cell count \> 200/ul will be included).

Sponsors & Collaborators

• Washington University School of Medicine: lead
• Ipsen: collaborator

Study Sites (1)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Related Links

• Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

Fluorouracil; Leucovorin; irinotecan sucrosofate; paricalcitol; Vitamin D

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes; Secosteroids; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• Kian-Huat Lim, M.D, Ph.D.

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 18, 2019
• First Posted: March 21, 2019
• Study Start: July 11, 2019
• Primary Completion: March 23, 2021
• Study Completion: July 2, 2022
• Last Updated: October 5, 2022

Record last verified: 2022-10

Data Sharing

• IPD Sharing: Will share
• Time Frame: Time frame for accessing IPD to be determined.
• Access Criteria: Access criteria for sharing IPD to be determined.

Locations

US (1)