Onvansertib for Small Cell Lung Cancer
Recruiting in Palo Alto (17 mi)
+1 other location
Overseen byTaofeek Owonikoko, MD, PhD
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Taofeek Owonikoko
Must not be taking: Investigational agents, Hematopoietic growth factors
Disqualifiers: Uncontrolled brain metastases, Active GI disorders, others
No Placebo Group
Prior Safety Data
Approved in 2 Jurisdictions
Trial Summary
What is the purpose of this trial?This trial is testing onvansertib, a drug that blocks an enzyme helping cancer cells grow, in patients with small cell lung cancer who can't use standard chemotherapy. By stopping the cancer cells from repairing themselves, the drug aims to slow down or stop their growth.
Will I have to stop taking my current medications?
The trial protocol does not specify if you must stop taking your current medications. However, you cannot participate if you have had chemotherapy within 4 weeks or radiotherapy within 2 weeks before starting the trial. It's best to discuss your current medications with the trial team.
What makes the drug Onvansertib unique for treating small cell lung cancer?
Onvansertib is unique because it targets specific molecular pathways involved in cancer cell division, which is different from the standard chemotherapy treatments that are not targeted. This approach may offer a new option for patients, especially since there are currently no molecularly targeted drugs approved for small cell lung cancer.
12345Eligibility Criteria
This trial is for adults over 18 with small cell lung cancer (SCLC) who have tried and not responded to or can't tolerate chemotherapy. They must be able to take oral medication, use contraception, and have a certain level of physical fitness (ECOG ≤2). People with more than two prior chemo treatments, active hepatitis B/C or HIV without approval, recent major surgery, ongoing serious illnesses, or untreated brain metastases cannot join.Inclusion Criteria
I've had 1 or 2 chemotherapy treatments for advanced lung cancer and can't tolerate standard treatments.
I have a tumor that can be measured with a scan.
I am over 18 years old.
+8 more
Exclusion Criteria
I haven't had chemotherapy, radiotherapy, or biologic agents recently.
I had major surgery less than 2 weeks ago or am still dealing with its side effects.
I am willing and able to follow the study rules and work with the research team.
+7 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Safety Run-in
Initial 6 participants are closely monitored to establish safety and tolerability of onvansertib at the dose of 15 mg/m2 on D1-D14 of a 21-day cycle
3 weeks
Multiple visits for monitoring
Treatment
Participants receive onvansertib treatment in a 21-day cycle, with dose adjustments based on safety evaluations
Up to 42 months
Follow-up
Participants are monitored for safety and effectiveness after treatment
Up to 3.5 years
Participant Groups
The trial is testing Onvansertib's safety and effectiveness in treating SCLC. Onvansertib blocks PLK-1 enzymes that help cancer cells repair themselves. Participants will receive this drug after failing standard platinum-based therapies and up to two lines of cytotoxic chemotherapy for extensive stage disease.
1Treatment groups
Experimental Treatment
Group I: Single Treatment ArmExperimental Treatment1 Intervention
Onvansertib
Onvansertib is already approved in United States, European Union for the following indications:
🇺🇸 Approved in United States as Onvansertib for:
- Acute Myeloid Leukemia (AML) - Orphan Drug Designation
🇪🇺 Approved in European Union as Onvansertib for:
- Acute Myeloid Leukemia (AML) - Orphan Drug Designation
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
University of Maryland Greenebaum Comprehensive Cancer CenterBaltimore, MD
UPMC Hillman Cancer CenterPittsburgh, PA
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Who Is Running the Clinical Trial?
Taofeek OwonikokoLead Sponsor
National Institutes of Health (NIH)Collaborator
Cardiff OncologyIndustry Sponsor
National Cancer Institute (NCI)Collaborator
References
A phase I trial of sorafenib combined with cisplatin/etoposide or carboplatin/pemetrexed in refractory solid tumor patients. [2021]Sorafenib has demonstrated single agent activity in non-small cell (NSCLC) and small cell lung cancer (SCLC). Carboplatin/pemetrexed (CbP) and cisplatin/etoposide (PE) are commonly used in the treatment of these diseases.
Development of molecularly targeted agents and immunotherapies in small cell lung cancer. [2021]Small cell lung cancer (SCLC) is a smoking-induced malignancy with multiple toxin-associated mutations, which accounts for 15% of all lung cancers. It remains a clinical challenge with a rapid doubling time, early dissemination and poor prognosis. Despite multiple clinical trials in SCLC, platinum-based chemotherapy remains the mainstay of treatment in the first line advanced disease setting; good initial responses are nevertheless inevitably followed by disease relapse and survival ultimately remains poor. There are currently no molecularly targeted agents licenced for use in SCLC. Advances in sequencing the cancer genome and other high-throughput profiling technologies have identified aberrant pathways and mechanisms implicated in SCLC development and progression. Novel anti-tumour therapeutics that impact these putative targets are now being developed and investigated in SCLC. In this review, we discuss novel anti-tumour agents assessed in SCLC with reference to the complex molecular mechanisms implicated in SCLC development and progression. We focus on novel DNA damage response inhibitors, immune checkpoint modulators and antibody-drug conjugates that have shown promise in SCLC, and which may potentially transform treatment strategies in this disease. Finally, we envision the future management of SCLC and propose a biomarker-driven translational treatment paradigm for SCLC that incorporates next generation sequencing studies with patient tumours, circulating plasma DNA and functional imaging. Such modern strategies have the potential to transform the management and improve patient outcomes in SCLC.
Absence of Biomarker-Driven Treatment Options in Small Cell Lung Cancer, and Selected Preclinical Candidates for Next Generation Combination Therapies. [2022]Lung cancer is the second most common cancer in the United States, and small cell lung cancer (SCLC) accounts for about 15% of all lung cancers. In SCLC, more than other malignancies, the standard of care is based on clinical demonstration of efficacy, and less on a mechanistic understanding of why certain treatments work better than others. This is in large part due to the virulence of the disease, and lack of clinically or biologically relevant biomarkers beyond routine histopathology. While first line therapies work in the majority of patients with extensive stage disease, development of resistance is nearly universal. Although neuroendocrine features, Rb and p53 mutations are common, the current lack of actionable biomarkers has made it difficult to develop more effective treatments. Some progress has been made with the application of immune checkpoint inhibitors. There are new agents, such as lurbinectedin, that have completed late-phase clinical testing while other agents are still in the pre-clinical phase. ONC201/TIC10 is an imipridone with strong in vivo and in vitro antitumor properties and activity against neuroendocrine tumors in phase 1 clinical testing. ONC201 activates the cellular integrated stress response and induces the TRAIL pro-apoptotic pathway. Combination treatment of lurbinectedin with ONC201 are currently being investigated in preclinical studies that may facilitate translation into clinical trials for SCLC patients.
CHK1 Inhibition in Small-Cell Lung Cancer Produces Single-Agent Activity in Biomarker-Defined Disease Subsets and Combination Activity with Cisplatin or Olaparib. [2021]Effective targeted therapies for small-cell lung cancer (SCLC), the most aggressive form of lung cancer, remain urgently needed. Here we report evidence of preclinical efficacy evoked by targeting the overexpressed cell-cycle checkpoint kinase CHK1 in SCLC. Our studies employed RNAi-mediated attenuation or pharmacologic blockade with the novel second-generation CHK1 inhibitor prexasertib (LY2606368), currently in clinical trials. In SCLC models in vitro and in vivo, LY2606368 exhibited strong single-agent efficacy, augmented the effects of cisplatin or the PARP inhibitor olaparib, and improved the response of platinum-resistant models. Proteomic analysis identified CHK1 and MYC as top predictive biomarkers of LY2606368 sensitivity, suggesting that CHK1 inhibition may be especially effective in SCLC with MYC amplification or MYC protein overexpression. Our findings provide a preclinical proof of concept supporting the initiation of a clinical efficacy trial in patients with platinum-sensitive or platinum-resistant relapsed SCLC. Cancer Res; 77(14); 3870-84. ©2017 AACR.
Targeted therapies in small cell lung cancer: a review. [2021]Small cell lung cancer (SCLC) is an aggressive form of lung cancer that is characterized by a rapid doubling time, early onset of dissemination and high sensitivity to chemotherapy. Despite the potential for cure in patients with limited disease with concurrent chemoradiation and an initial good response to chemotherapy in extensive disease, there is a high chance of disease relapse with an overall poor median survival for both stages. With increasing translational research and a better understanding of the molecular basis of cancer, a number of molecular targets have been identified in various preclinical studies. This review summarizes potentially viable targets and new agents that have been developed and employed in recent, ongoing and future clinical trials to attempt to improve clinical outcomes in this disease.