AzTrials
AzTrials

Locally Advanced Pancreatic Ductal AdenocarcinomaPhase 2NCT06398587

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

A Phase 2 study testing Onvansertib, Gemcitabine and Nab-paclitaxel in people with Locally Advanced Pancreatic Ductal Adenocarcinoma and Metastatic Pancreatic Ductal Adenocarcinoma, run by OHSU Knight Cancer Institute at 1 site in United States.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
Search all trials

Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Onvansertib, Gemcitabine and Nab-paclitaxel
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
1 siteUnited States
Study dates
1 Aug 2024to 7 Jun 2027
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 18Show fewer
  • 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
  • Participants of childbearing potential (POCBP) must agree to abstain from sexual intercourse or use effective non-hormonal methods of contraception starting with the first dose of study therapy through 90 days from the last dose of study intervention
  • POCBP may participate provided they have a negative serum pregnancy test at screening and a negative serum OR urine pregnancy test within 7 days of starting treatment
  • Sperm-producing participants must agree to abstain from sexual intercourse or use effective contraception starting with the first dose through 1 month after last dose of study intervention

Who cannot join

  • 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
Show all 17Show fewer
  • 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.)
  • Participant is pregnant or breastfeeding, or expecting to conceive or sire children within the projected duration of the trial, starting with the screening visit through 90 days after the last dose of trial treatment
  • Judgment by the investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions and requirements

Trial locations and contacts

1 site in 1 country.

United States1 site

  • OHSU Knight Cancer Institute

    Portland, Oregon, 97239

Other trials in United States

About this study

Official title: An Open-Label, Phase II Trial to Assess Efficacy and Safety of Onvansertib in Combination With Gemcitabine and Nab-Paclitaxel in Patients With Previously Untreated, Locally-Advanced or Unresectable Pancreatic Adenocarcinoma

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.

Read the detailed description

PRIMARY OBJECTIVE:

  1. To assess preliminary response to treatment with onvansertib and gemcitabine and nab-paclitaxel (GnP).

SECONDARY OBJECTIVES:

  1. To assess the safety of onvansertib in combination with GnP. II. To assess the rate of disease control following treatment with onvansertib and GnP in patients with PDAC.

III. To estimate the duration of response (DOR). IV. To estimate the time to disease progression. V. To estimate the progression-free survival associated with onvansertib and GnP.

VI. To estimate the overall survival associated with onvansertib and GnP.

EXPLORATORY OBJECTIVE:

  1. To evaluate therapy induced changes in the tumor and tumor ecosystem.

OUTLINE: This is a safety lead-in study of onvansertib in combination with GnP, followed by a phase II study. Patients are assigned to 1 of 2 groups.

GROUP 1: Patients receive onvansertib orally (PO) once daily (QD) on days 1-5, 8-12, and 15-19 and gemcitabine intravenously (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, computed tomography (CT), magnetic resonance imaging (MRI), and/or positron emission tomography (PET) throughout the trial.

GROUP 2: 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.

Upon completion of the study treatment, patients are followed up at 30 days and then every 3 months for up to 12 months from date of last dose of study drug.

Being tested
Onvansertib, Gemcitabine, Nab-paclitaxel, Electrocardiography, Magnetic Resonance Imaging
Medical subject headings
Pancreatic Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • OnvansertibDrug

    Also called NMS-1286937, PCM 075, PCM-075, PLK-1 Inhibitor PCM-075

    Given PO

  • GemcitabineDrug

    Also called dFdC, dFdCyd, Difluorodeoxycytidine

    Given IV

  • Nab-paclitaxelDrug

    Also called ABI 007, ABI-007, Abraxane, Albumin-bound Paclitaxel

    Given IV

  • ElectrocardiographyProcedure or surgery

    Also called ECG, EKG

    Undergo electrocardiography

  • Magnetic Resonance ImagingProcedure or surgery

    Also called Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan

    Undergo MRI

  • Positron Emission TomographyProcedure or surgery

    Also called Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron emission tomography (procedure)

    Undergo PET

  • Biospecimen CollectionProcedure or surgery

    Also called Biological Sample Collection, Specimen Collection

    Undergo blood sample collection

  • Biospecimen CollectionProcedure or surgery

    Also called Biological Sample Collection, Biospecimen Collected, Specimen Collection

    Undergo tumor biopsy

  • Computed TomographyProcedure or surgery

    Also called CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography

    Undergo CT

Study groups in NCT06398587
Study groupRoleWhat they receive
Group 1 (onvansertib, GnP)ExperimentalPatients 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.
Receives: 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)ExperimentalPatients 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.
Receives: Drug: Onvansertib; Drug: Gemcitabine; Drug: Nab-paclitaxel; Procedure: Electrocardiography; Procedure: Magnetic Resonance Imaging; Procedure: Positron Emission Tomography; Procedure: Biospecimen Collection; Procedure: Computed Tomography

What is being measured

The primary outcome is the main question the study is designed to answer.

  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).

    Measured: Up to 3 months after last dose of study intervention

Secondary outcomes (6)

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

    Using safety analysis set, the incidence of having treatment-emergent AEs and SAEs per Common Terminology Criteria for Adverse Events (CTCAE) 5.0 will be determined for participants that received at least one dose of onvansertib. The 95% CI will be reported with the point estimate of toxicity rate.

    Measured: Up to 30 days after last dose of study intervention

  2. Disease control rate (DCR)

    Defined as percentage of participants who have achieved CR, PR, or stable disease (SD) (per RECIST v1.1 criteria) for at least 16 weeks from initiating study treatment. Using the Group 1 efficacy analysis set, the estimate of DCR will be reported with 95% exact CI.

    Measured: Up to 1 year after last dose of study intervention

  3. Duration of response (DOR)

    Using the Group 1 efficacy analysis set, DOR will characterized using the Kaplan-Meier (KM) method at specific timepoints (e.g., 3, 6, 9, 12, and 24 months; median DOR), along with corresponding 95% CI.

    Measured: 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

  4. Time to progression (TTP)

    Using the Group 1 efficacy analysis set, the time to progression distribution will be characterized using the KM method. KM curves of TTP will be presented. Median TTP, quartiles and TTP rate after specific time points (e.g., 3, 6, 9, 12, and 24 months; median TTP) will be estimated from the survival curves. All these parameter estimates will be reported together with their 95% CIs.

    Measured: 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

  5. Progression-free survival (PFS)

    The estimated distribution of the PFS will be plotted using KM curves and reported with median survival and 95% CIs if available.

    Measured: 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

  6. Overall survival (OS)

    The estimated distribution of the OS will be plotted using KM curves and reported with median survival and 95% CIs if available.

    Measured: From date of first dose of study drug to the date of death by any cause, assessed up to 1 year after last dose of study intervention

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted3 May 2024
  2. Study start1 Aug 2024 (estimated)
  3. Primary completion4 May 2026 (estimated)
  4. Study completion7 Jun 2027 (estimated)

Why it stopped: Sponsor withdrawal

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06398587
Sponsor's protocol ID
STUDY00026545
Other IDs
NCI-2024-02588, STUDY00026545
Status last verified
Jul 2024
First submitted
30 Apr 2024
Last updated
19 Jul 2024
Results posted
No
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Onvansertib, Gemcitabine and Nab-paclitaxel in people with Locally Advanced Pancreatic Ductal Adenocarcinoma and Metastatic Pancreatic Ductal Adenocarcinoma, run by OHSU Knight Cancer Institute at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 18 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 19 Jul 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Objective response rate (ORR) (time frame: Up to 3 months after last dose of study intervention). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06398587.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Jul 2024.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in