Study of PLK1 Inhibitor, Onvansertib, in Relapsed Small Cell Lung Cancer
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorUniversity of Maryland, Baltimore
About this trial
This phase II clinical trial will study the safety and efficacy of onvansertib to treat patients with small cell lung cancer (SCLC) who have either not responded to or are unable to tolerate chemotherapy. Onvansertib is a drug that inhibits polo-like kinase 1 (PLK-1), an enzyme that is over-expressed in many cancer cells and is involved in cellular repair.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Patients must have histologically or cytologically confirmed small cell lung cancer
Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as >20 mm with conventional techniques or as >10 mm with spiral CT scan. See Section 8for the evaluation of measurable disease.
Patient must have failed or found to be intolerant of standard frontline platinum-based regimens and not more than two lines of cytotoxic chemotherapy treatment in total for extensive stage disease. Maintenance immunotherapy counts as part of the frontline therapy, while prior chemotherapy for limited stage disease will not count toward this total if completed more than 12 months before initiation of protocol therapy. Retreatment with the original chemotherapy regimen for sensitive relapsed SCLC counts as a separate line of treatment.
Adult patients with age >18 years. Because no dosing or adverse event data are currently available on the use of arsenic trioxide in patients <18 years of age, children are excluded from this study but will be eligible for future pediatric single-agent trials, if applicable.
Disqualifiers
Treatment with chemotherapy (within 4 weeks; 6 weeks for nitrosoureas or mitomycin C); radiotherapy or biologic agents (within 2 weeks) prior to first dose of onvansertib or those persistent, clinically significant, grade ≥2 adverse events due to agents administered more than 4 weeks earlier.
Patients may not be receiving any other investigational agents (Use of conventional external beam radiation therapy will be allowed during protocol therapy solely for palliation of localized painful lesions or bone lesions at risk of fracture provided the radiation field does not encompass any selected target lesions required for assessment).
Patients with uncontrolled symptomatic brain metastases. Subjects with a history of central nervous system (CNS) metastases must have documentation of stable brain imaging after completion of definitive treatment and prior to first dose of Study Drug. Patients must be off or on a stable dose of corticosteroids (not more than 10mg prednisone or equivalent). Definitive treatment may include surgical resection, whole brain irradiation, and/or stereotactic radiation therapy.
Patients with active GI disorders likely to impair the absorption of oral medications
Trial design
Design model
Single group
Treatments tested in this trial
Onvansertib
DrugOnvansertib at a dose of 15 mg/m2 orally on Days 1-14 of a 21-day cycle. Treatment will continue until disease progression or intolerable toxicity.
Treatment groups
37 Participants
are divided into 1 treatment groupGroup A: Single Treatment ArmExperimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
Objective Response Rate (ORR)
The proportion of patients having either a complete response (CR) or partial response (PR) (as best response), per RECIST 1.1. Complete Response (CR): Disappearance of all target lesions. For non-target lesions, CR is the disappearance of all non-target lesions and normalization of tumor marker level. Partial Response (PR): At least a 30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD.
Time frame
Up to 42 months (cohort)Secondary outcomes
1
Adverse Events (AEs) and Serious Adverse Events (SAEs)
The number of patients incurring specific Adverse Events or Serious Adverse Events that occur from first day of treatment, considered to be possibly, probably or definitely related to study treatment, per Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Patients experiencing multiple AEs of the same type will be reported by only the most severe grade.
Time frame
Up to 3.5 years2
Progression-free survival (PFS)
The median number of months from start of treatment to time of disease progression or death (from any cause), whichever occurs first. Progressive Disease (PD) as defined by RECIST v1.1 for target lesions: At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. For non-target lesions: Appearance of one or more new lesions and/or unequivocal progression of existing nontarget lesions. Unequivocal progression should not normally trump target lesion status. It must be representative of overall disease status change, not a single lesion increase.
Time frame
Up to 3.5 years3
Overall survival (OS)
The median number of months from start of treatment to time of death from any cause.
Time frame
Up to 3.5 yearsSponsors and contacts
Click on the lead sponsor to view all of their trials.
University of Maryland, Baltimore
Lead sponsor
Cardiff Oncology
Collaborator
National Cancer Institute (NCI)
Collaborator
Source ClinicalTrials.gov