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

• ClinicalTrials.gov Identifier: NCT04752696
• Recruitment Status: Recruiting
• First Posted: February 12, 2021
• Last Update Posted: December 16, 2022
• Sponsor: Cardiff Oncology
• Information provided by (Responsible Party): Cardiff Oncology

Study Description

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).

Condition or disease	Intervention/treatment	Phase
Pancreatic Ductal Adenocarcinoma	Drug: Onvansertib; Drug: Nanoliposomal irinotecan; Drug: Leucovorin; Drug: Fluorouracil	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 40 participants
• Allocation: Non-Randomized
• Intervention Model: Sequential Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: May 3, 2021
• Estimated Primary Completion Date: February 13, 2023
• Estimated Study Completion Date: March 11, 2024

Arms and Interventions

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 Name: PCM-075; Drug: Nanoliposomal irinotecan; Intravenous infusion; Other Names: Onivyde; Nal-IRI; Drug: Leucovorin; Intravenous infusion; Drug: Fluorouracil; Intravenous infusion; Other Name: 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 Name: PCM-075; Drug: Nanoliposomal irinotecan; Intravenous infusion; Other Names: Onivyde; Nal-IRI; Drug: Leucovorin; Intravenous infusion; Drug: Fluorouracil; Intravenous infusion; Other Name: 5-FU

Outcome Measures

Primary Outcome Measures :

1. Overall Response Rate (ORR) [ Time Frame: 6 months ]

Secondary Outcome Measures :

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

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

Contacts

Contact: Cardiff Oncology; 858-952-7570; info@cardiffoncology.com

Locations

United States, Arizona

Mayo Clinic Phoenix; Recruiting

Phoenix, Arizona, United States, 85054

Contact: Clinical Trial Referral Office 855-776-0015

United States, Florida

Mayo Clinic Jacksonville; Recruiting

Jacksonville, Florida, United States, 32224

Contact: Clinical Trial Referral Office 855-776-0015

United States, Kansas

University of Kansas Medical Center; Recruiting

Westwood, Kansas, United States, 66205

United States, Minnesota

Mayo Clinic Rochester; Recruiting

Rochester, Minnesota, United States, 55905

Contact: Clinical Trials Referral Office 855-776-0015

United States, Nebraska

University of Nebraska Medical Center; Recruiting

Omaha, Nebraska, United States, 68198

United States, Virginia

Inova Schar Cancer Institute; Recruiting

Fairfax, Virginia, United States, 22031

Sponsors and Collaborators

Cardiff Oncology

More Information

• Responsible Party: Cardiff Oncology
• ClinicalTrials.gov Identifier: NCT04752696
• Other Study ID Numbers: CRDF-001
• First Posted: February 12, 2021
• Last Update Posted: December 16, 2022
• Last Verified: December 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Cardiff Oncology:

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

Additional relevant MeSH terms:

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Leucovorin; Fluorouracil; Irinotecan; Onvansertib; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Topoisomerase I Inhibitors; Topoisomerase Inhibitors; Enzyme Inhibitors; Antidotes; Protective Agents; Vitamin B Complex; Vitamins; Micronutrients; Protein Kinase Inhibitors