Onvansertib in Combination With Gemcitabine and Nab-paclitaxel for the Treatment of Patients With Locally-advanced, Unresectable, or Metastatic Pancreatic Ductal Adenocarcinoma

NCT06398587 | Withdrawn Phase 2 FDA Drug

• 2 other identifiers: STUDY00026545NCI-2024-02588
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial studies how well onvansertib in combination with gemcitabine and nab-paclitaxel works in treating patients with pancreatic ductal carcinoma (PDAC) that has spread to nearby tissue or lymph nodes (locally advanced), that cannot be removed by surgery (unresectable), or that has spread from where it first started (primary site) to other places in the body (metastatic). Onvansertib is a small chemical molecule that binds and stops the function of of PLK1 in tumor cells. By attacking the PLK1 protein, onvansertib is thought to reduce tumor cells ability to replicate and grow; causing them to die. Chemotherapy drugs, such as gemcitabine and nab-paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving chemotherapy with onvansertib may kill more tumor cells in patients with locally-advanced, unresectable, or metastatic pancreatic ductal carcinoma.

Conditions

Locally Advanced Pancreatic Ductal Adenocarcinoma; Metastatic Pancreatic Ductal Adenocarcinoma; Stage II Pancreatic Cancer AJCC v8; Stage III Pancreatic Cancer AJCC v8; Stage IV Pancreatic Cancer AJCC v8; Unresectable Pancreatic Adenocarcinoma

Outcome Measures

Primary Outcomes (1)

• Objective response rate (ORR)

  Defined as the percentage of participants that achieve a best overall response of complete response (CR) or partial response (PR) (per Response Evaluation Criteria in Solid Tumors version \[v\]1.1 criteria). Using the Group 1 efficacy analysis set, an estimate of ORR will be reported with 95% exact confidence interval (CI).

  Up to 3 months after last dose of study intervention

Secondary Outcomes (6)

• Incidence of treatment-emergent adverse events (AEs) and serious AEs

  Up to 30 days after last dose of study intervention

• Disease control rate (DCR)

  Up to 1 year after last dose of study intervention

• Duration of response (DOR)

  From the date of first response (CR, PR, or SD ≥ 16 weeks [per RECIST v1.1 criteria]) to date of disease progression or death, whichever occurs first, assessed up to 1 year after last dose of study intervention

• Time to progression (TTP)

  From the start of study intervention until first objectively documented date of disease progression, assessed up to 1 year after last dose of study intervention

• Progression-free survival (PFS)

  From first dose of study drug to the first date of objectively documented disease progression, or death by any cause, assessed up to 1 year from last dose of study intervention

Study Arms (2)

Group 1 (onvansertib, GnP)

EXPERIMENTAL

Patients receive onvansertib PO QD on days 1-5, 8-12, and 15-19 and gemcitabine IV and nab-paclitaxel IV on days 1, 8, and 15. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo electrocardiography at baseline, as well as blood sample collection, tumor biopsy, CT, MRI, and/or PET throughout the trial.

Drug: Onvansertib; Drug: Gemcitabine; Drug: Nab-paclitaxel; Procedure: Electrocardiography; Procedure: Magnetic Resonance Imaging; Procedure: Positron Emission Tomography; Procedure: Biospecimen Collection; Procedure: Computed Tomography

Group 2 (onvansertib monotherapy lead-in, GnP)

EXPERIMENTAL

Patients receive onvansertib PO QD on days 1-10. Patients then receive onvansertib, gemcitabine, and nab-paclitaxel as in Group 1. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo electrocardiography at baseline, as well as blood sample collection, tumor biopsy, CT, MRI, and/or PET throughout the trial.

Drug: Onvansertib; Drug: Gemcitabine; Drug: Nab-paclitaxel; Procedure: Electrocardiography; Procedure: Magnetic Resonance Imaging; Procedure: Positron Emission Tomography; Procedure: Biospecimen Collection; Procedure: Computed Tomography

Interventions

Onvansertib DRUG

Given PO

Also known as: NMS-1286937, PCM 075, PCM-075, PLK-1 Inhibitor PCM-075, PLK1 Inhibitor PCM-075, Polo-like Kinase 1 Inhibitor NMS-1286937, Polo-like Kinase 1 Inhibitor PCM-075

Group 1 (onvansertib, GnP); Group 2 (onvansertib monotherapy lead-in, GnP)

Gemcitabine DRUG

Given IV

Also known as: dFdC, dFdCyd, Difluorodeoxycytidine

Group 1 (onvansertib, GnP); Group 2 (onvansertib monotherapy lead-in, GnP)

Nab-paclitaxel DRUG

Given IV

Also known as: ABI 007, ABI-007, Abraxane, Albumin-bound Paclitaxel, Albumin-Stabilized Nanoparticle Paclitaxel, Nanoparticle Albumin-bound Paclitaxel, Nanoparticle Paclitaxel, Paclitaxel Albumin, paclitaxel albumin-stabilized nanoparticle formulation, Paclitaxel Nanoparticle Albumin-bound, Paclitaxel Protein-Bound, Protein-bound Paclitaxel

Group 1 (onvansertib, GnP); Group 2 (onvansertib monotherapy lead-in, GnP)

Electrocardiography PROCEDURE

Undergo electrocardiography

Also known as: ECG, EKG

Group 1 (onvansertib, GnP); Group 2 (onvansertib monotherapy lead-in, GnP)

Magnetic Resonance Imaging PROCEDURE

Undergo MRI

Also known as: Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MR, MR Imaging, MRI, MRI Scan, MRIs, NMR Imaging, NMRI, Nuclear Magnetic Resonance Imaging, sMRI, Structural MRI

Group 1 (onvansertib, GnP); Group 2 (onvansertib monotherapy lead-in, GnP)

Positron Emission Tomography PROCEDURE

Undergo PET

Also known as: Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron emission tomography (procedure), Positron Emission Tomography Scan, Positron-Emission Tomography, proton magnetic resonance spectroscopic imaging, PT

Group 1 (onvansertib, GnP); Group 2 (onvansertib monotherapy lead-in, GnP)

Biospecimen Collection PROCEDURE

Undergo blood sample collection

Also known as: Biological Sample Collection, Specimen Collection

Group 1 (onvansertib, GnP); Group 2 (onvansertib monotherapy lead-in, GnP)

Computed Tomography PROCEDURE

Undergo CT

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, Computerized Tomography (CT) scan, CT, CT Scan, tomography

Group 1 (onvansertib, GnP); Group 2 (onvansertib monotherapy lead-in, GnP)

Eligibility Criteria

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

You may qualify if:

• Must provide written informed consent before any study-specific procedures or interventions are performed
• Must be ≥ 18 years old at the time of informed consent
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
• Histologically or cytologically-proven adenocarcinoma of the exocrine pancreas with locally advanced or metastatic disease
• Must not have received prior radiotherapy, surgery, chemotherapy or investigational therapy for the treatment of metastatic disease. Prior palliative radiotherapy of metastases for alleviation of pain is permitted provided that irradiated metastases are not target lesions
• Patient must be eligible to receive GnP regimen for the treatment of their PDAC in accordance with institutional standards
• Must have measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1
• Must have at least one disease lesion that is amenable to biopsy procedures performed per institutional standards
• Group 1 participant must agree to undergo two (2) research biopsies
• Group 2 participants must agree to undergo three (3) research biopsies
• Hemoglobin ≥ 8.0 g/dL
• Absolute neutrophil count (ANC) ≥ 1.5 x 10\^9/L (\> 1500 per mm\^3)
• Platelet count ≥ 100 x 10\^9/L (\> 100,000 per mm\^3);
• Creatinine ≤ 1.5 x upper limit of normal (ULN), or measured or calculated creatinine clearance \> 50 mL/min/1.73 m\^2 (per Cockcroft-Gault equation)
• Aspartate aminotransferase (AST)/alanine aminotransferase (ALT): ≤ 3 x ULN, or ≤ 5 x ULN in presence of liver metastases

You may not qualify if:

• Concomitant use of other anti-cancer therapy (chemotherapy, immunotherapy, hormonal therapy (hormone replacement therapy is acceptable), radiotherapy (except for palliative), biological therapy or other novel agent) or live virus and live bacterial vaccines while receiving study medication
• Prior treatment with a PLK1 inhibitor
• Known severe hypersensitivity to onvansertib, gemcitabine, or nab-paclitaxel, or to any excipient of these medicinal products, or history of allergic reactions attributed to compounds of similar chemical or biologic composition
• Major surgery within 6 weeks prior to enrollment
• Uncontrolled intercurrent illness including symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, and myocardial infarction within 3 months of initiating study intervention
• QT interval with Fridericia's correction (QTcF) \> 470 milliseconds
• The QTcF should be calculated based on a mean of triplicate electrocardiogram (ECGs). In the case of potentially correctible causes of QT prolongation (e.g., medications, hypokalemia), the triplicate ECG may be repeated once during Screening and that result may be used to determine eligibility
• Use of concomitant medications known to increase QTc or risk of Torsades. These drugs should only be used if there are no other alternatives and only with appropriate monitoring (i.e., electrocardiograms)
• Presence of risk factors for torsade de pointes, including family history of Long QT Syndrome or uncorrected hypokalemia
• Known dysphagia, short-gut syndrome, gastroparesis, or other conditions that limit the ingestion or gastrointestinal absorption of drugs administered orally
• Use of strong CYP3A4 or UGT1A1 inhibitors or strong CYP3A4 inducers. Individuals currently receiving these agents who are able to switch to alternate therapy are still eligible for participation
• CYP3A4 or UGT1A1 inhibitors should be stopped at least one week prior to the first dose of onvansertib
• CYP3A4 inducers should be stopped at least two weeks prior to the first dose of onvansertib
• Psychiatric illness/social situations that would limit compliance with study requirements
• Any concurrent severe and/or uncontrolled medical condition (e.g. uncontrolled diabetes, infection, hypertension, etc.)

Sponsors & Collaborators

• OHSU Knight Cancer Institute: lead
• Oregon Health and Science University: collaborator

Study Sites (1)

OHSU Knight Cancer Institute

Portland, Oregon, 97239, United States

Location

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

onvansertib; Gemcitabine; 130-nm albumin-bound paclitaxel; Albumin-Bound Paclitaxel; Taxes; Magnetic Resonance Spectroscopy; Specimen Handling

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Paclitaxel; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Albumins; Proteins; Amino Acids, Peptides, and Proteins; Economics; Health Care Economics and Organizations; Spectrum Analysis; Chemistry Techniques, Analytical; Investigative Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis

Study Officials

• Charles D Lopez

  OHSU Knight Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: April 30, 2024
• First Posted: May 3, 2024
• Study Start: August 1, 2024
• Primary Completion: May 4, 2026
• Study Completion (Estimated): June 7, 2027
• Last Updated: July 19, 2024

Record last verified: 2024-07

Locations

US (1)