Onvansertib in Combination With Nanoliposomal Irinotecan, Leucovorin, and Fluorouracil for Second-Line Treatment of Participants With Metastatic Pancreatic Ductal Adenocarcinoma

A Phase 2 Study of Onvansertib in Combination With Nanoliposomal Irinotecan, Leucovorin, and Fluorouracil for Second-Line Treatment of Patients With Metastatic Pancreatic Ductal Adenocarcinoma

The main objective of this trial is to assess the efficacy of onvansertib in combination with nanoliposomal irinotecan (nal-IRI), leucovorin, and fluorouracil (5-FU) for treatment of participants with histologically confirmed metastatic pancreatic ductal adenocarcinoma (PDAC).

Study Overview

• Status: Active, not recruiting
• Conditions: Pancreatic Ductal Adenocarcinoma
• Intervention / Treatment: Drug: Onvansertib; Drug: Leucovorin; Drug: Nanoliposomal irinotecan; Drug: Fluorouracil

• Study Type: Interventional
• Enrollment (Actual): 43
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Nancy Sherman; Phone Number: 858-952-7570; Email: info@cardiffoncology.com

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85054
      • Mayo Clinic Phoenix
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic Jacksonville
  • Kansas
    • Westwood, Kansas, United States, 66205
      • University of Kansas Medical Center
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic Rochester
  • Nebraska
    • Omaha, Nebraska, United States, 68198
      • University of Nebraska Medical Center
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Inova Schar Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Histologically or cytologically confirmed metastatic PDAC
• Has received 1 prior gemcitabine-based chemotherapy as first line therapy for metastatic disease. Progression after completion of neoadjuvant or adjuvant therapy of < 6 months in duration is considered 1 line of therapy for metastatic disease
• Has measurable disease according to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1), defined as at least 1 lesion that can be accurately measured in at least 1 dimension (longest diameter to be recorded) as > 20 mm with conventional techniques or as > 10 mm with spiral computed tomography (CT) scan
• Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1
• Must be willing and able to undergo a tissue biopsy at screening; participants who, in the opinion of the investigator, do not have tissue that is accessible for biopsy are excepted from this criterion
• Women of childbearing potential: (defined as not post-menopausal for 12 months or no previous surgical sterilization) and fertile men must agree to use adequate contraception for the duration of study participation and for 4 months after the last dose of nal-IRI. Male subjects must agree to refrain from sperm donation during the study and for 4 months after the last dose of nal-IRI
• Ability to understand and the willingness to sign a written informed consent document. Signed informed consent form must be obtained prior to initiation of study evaluations and/or activities
• International Normalized Ratio (INR) < 1.5 unless on warfarin
• Participants with prior malignancy and who were treated with no evidence of active disease more than 2 years from initial diagnosis are eligible
• Age ≥ 18 years
• Participants must have adequate organ and bone marrow function

Exclusion Criteria:

• Prior treatment with irinotecan, nal-IRI, or investigational PLK1 inhibitor
• Uncontrolled intercurrent illness including symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, and myocardial infarction within 3 months of initiation of therapy
• History of interstitial pneumonitis or interstitial lung disease
• Participants with microsatellite instability-high (MSI-H) tumors with no prior immune checkpoint inhibitor exposure
• Pregnancy or lactation
• Participant has active and uncontrolled bacterial, viral, or fungal infection(s) requiring systemic therapy
• QT interval with Fridericia's correction (QTcF) > 470 milliseconds. The QTcF should be calculated as the arithmetic mean of the QTcF on triplicate electrocardiograms (ECGs). In the case of potentially correctible causes of QT prolongation, (eg, medications, hypokalemia), the triplicate ECG may be repeated once during Screening and that result may be used to determine eligibility
• Planned concomitant use of medications known to prolong the QT/QTc interval
• Participant has undergone major surgical resection within 4 weeks prior to enrollment
• Participant received radiotherapy, surgery, chemotherapy, or an investigational therapy within 2 weeks prior to study entry
• Participant has serious medical risk factors involving any of the major organ systems such that the investigator considers it unsafe for the participant to receive an experimental research drugs
• Serious psychiatric or medical conditions that could interfere with treatment
• Major bleeding in the last 4 weeks
• More than 1 prior chemotherapy regimen administered in the metastatic setting
• Unable or unwilling to swallow oral medication
• Use of strong CYP3A4 or UGT1A1 inhibitors or strong CYP3A4 inducers. Participants currently receiving these agents who are able to switch to alternate therapy are not excluded. Inhibitors should be stopped at least one week prior to the first dose of protocol therapy and inducers should be stopped at least two weeks prior to initiation of protocol therapy.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Safety Lead-in: Onvansertib + nal-IRI + leucovorin + 5-FU; The first 3 participants will be administered onvansertib orally once a day at a dosing schedule of 12 mg/m^2 on Day 1 to Day 10 for two cycles, where each cycle is 2 weeks. Depending on the number of dose limiting toxicities (DLTs) experienced in the first 3 participants, additional participants may receive different dosing schedules, determining the dosing schedule to be used in the treatment period. Onvansertib will be administered in combination with 70 mg/m^2 nanoliposomal irinotecan (nal-IRI), 400 mg/m^2 leucovorin and 2400 mg/m^2 fluorouracil (5-FU).	Drug: Onvansertib; Oral capsule; Other Names: PCM-075; Drug: Leucovorin; Intravenous infusion; Drug: Nanoliposomal irinotecan; Intravenous infusion; Other Names: Onivyde; Nal-IRI; Drug: Fluorouracil; Intravenous infusion; Other Names: 5-FU
Experimental: Treatment Period: Onvansertib + nal-IRI + leucovorin + 5-FU; Participants will be administered onvansertib at the dosing schedule selected based on the results of the safety lead-in, in cycles of 2 weeks. Onvansertib will be administered in combination with 70 mg/m^2 nanoliposomal irinotecan (nal-IRI), 400 mg/m^2 leucovorin and 2400 mg/m^2 fluorouracil (5-FU).	Drug: Onvansertib; Oral capsule; Other Names: PCM-075; Drug: Leucovorin; Intravenous infusion; Drug: Nanoliposomal irinotecan; Intravenous infusion; Other Names: Onivyde; Nal-IRI; Drug: Fluorouracil; Intravenous infusion; Other Names: 5-FU

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Overall Response Rate (ORR)	Up to 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)		Up to 2 years
Disease Control Rate (DCR)		Up to 2 years
Duration of Response (DOR)		Up to 2 years
Number of Participants Who Experience a Treatment-emergent Adverse Event (TEAE)		Up to 2 years
Overall Response Rate (ORR) in Participants Who Receive At Least 2 Treatment Cycles	Each cycle is 2 weeks.	Up to 2 years
Reduction from Baseline in Serum CA19-9 Response		Baseline up to 2 years

Collaborators and Investigators

• Sponsor: Cardiff Oncology

Study record dates

Study Major Dates

• Study Start (Actual): February 3, 2021
• Primary Completion (Estimated): March 11, 2024
• Study Completion (Estimated): March 11, 2024

Study Registration Dates

• First Submitted: February 9, 2021
• First Submitted That Met QC Criteria: February 9, 2021
• First Posted (Actual): February 12, 2021

Study Record Updates

• Last Update Posted (Actual): November 29, 2023
• Last Update Submitted That Met QC Criteria: November 28, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: Fluorouracil; Pancreatic Ductal Adenocarcinoma; PLK1; PLK Inhibitor; Onvansertib; Leucovorin; Nanoliposomal irinotecan
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Carcinoma; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Protective Agents; Topoisomerase Inhibitors; Micronutrients; Protein Kinase Inhibitors; Vitamins; Topoisomerase I Inhibitors; Antidotes; Vitamin B Complex; Fluorouracil; Leucovorin; Irinotecan; Onvansertib
• Other Study ID Numbers: CRDF-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No