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

NCT04752696 | Completed Phase 2 FDA Drug

• 1 other identifier: CRDF-001
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 6

Brief Summary

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).

Conditions

Pancreatic Ductal Adenocarcinoma

Keywords

Pancreatic Ductal Adenocarcinoma; Onvansertib; Nanoliposomal irinotecan; Leucovorin; Fluorouracil; PLK1; PLK Inhibitor

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate (ORR)

  Up to 2 years

Secondary Outcomes (6)

• Number of Participants Who Experience a Treatment-emergent Adverse Event (TEAE)

  Up to 2 years

• Duration of Response (DOR)

  Up to 2 years

• Overall Response Rate (ORR) in Participants Who Receive At Least 2 Treatment Cycles

  Up to 2 years

• Overall Survival (OS)

  Up to 2 years

• Disease Control Rate (DCR)

  Up to 2 years

Study Arms (2)

Safety Lead-in: Onvansertib + nal-IRI + leucovorin + 5-FU

EXPERIMENTAL

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; Drug: Nanoliposomal irinotecan; Drug: Leucovorin; Drug: Fluorouracil

Treatment Period: Onvansertib + nal-IRI + leucovorin + 5-FU

EXPERIMENTAL

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; Drug: Nanoliposomal irinotecan; Drug: Leucovorin; Drug: Fluorouracil

Interventions

Onvansertib DRUG

Oral capsule

Also known as: PCM-075

Safety Lead-in: Onvansertib + nal-IRI + leucovorin + 5-FU; Treatment Period: Onvansertib + nal-IRI + leucovorin + 5-FU

Nanoliposomal irinotecan DRUG

Intravenous infusion

Also known as: Onivyde, Nal-IRI

Safety Lead-in: Onvansertib + nal-IRI + leucovorin + 5-FU; Treatment Period: Onvansertib + nal-IRI + leucovorin + 5-FU

Fluorouracil DRUG

Intravenous infusion

Also known as: 5-FU

Safety Lead-in: Onvansertib + nal-IRI + leucovorin + 5-FU; Treatment Period: Onvansertib + nal-IRI + leucovorin + 5-FU

Leucovorin DRUG

Intravenous infusion

Safety Lead-in: Onvansertib + nal-IRI + leucovorin + 5-FU; Treatment Period: Onvansertib + nal-IRI + leucovorin + 5-FU

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 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Cardiff Oncology: lead

Study Sites (6)

Mayo Clinic Phoenix

Phoenix, Arizona, 85054, United States

Location

Mayo Clinic Jacksonville

Jacksonville, Florida, 32224, United States

Location

University of Kansas Medical Center

Westwood, Kansas, 66205, United States

Location

Mayo Clinic Rochester

Rochester, Minnesota, 55905, United States

Location

University of Nebraska Medical Center

Omaha, Nebraska, 68198, United States

Location

Inova Schar Cancer Institute

Fairfax, Virginia, 22031, United States

Location

MeSH Terms

Interventions

onvansertib; irinotecan sucrosofate; Leucovorin; Fluorouracil

Intervention Hierarchy (Ancestors)

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 9, 2021
• First Posted: February 12, 2021
• Study Start: May 25, 2021
• Primary Completion: December 24, 2024
• Study Completion: December 24, 2024
• Last Updated: December 22, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (6)