Small Cell Lung Cancer Irinotecan and CDC2-like Kinase Inhibition Trial (SLICK Trial)
Trial statusRecruiting
Trial phasePhase 1, Phase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorWashington University School of Medicine
About this trial
Although small cell lung cancer (SCLC) responds dramatically to initial platinum-based chemotherapy, recurrences are nearly universal. The addition of atezolizumab, an immune checkpoint inhibitor, to front-line chemotherapy has recently demonstrated an improvement in overall survival (OS) in extensive stage SCLC (ES-SCLC). Subsequent lines of therapies are associated with modest efficacy in patients with relapsed disease, and the median overall survival is still 12 to 13 months at best.
Cirtuvivint is a small molecule inhibitor of the CDC2-like kinases (CLKs) and dual-specificity tyrosine-regulated kinases (DYRKs); inhibiting CLKs and DYRKs has been shown in preclinical models to cause tumor growth inhibition and sensitize cancer cells to cytotoxic chemotherapy.
This study is testing the hypothesis that adding cirtuvivint to chemotherapy in patients with relapsed SCLC will be well tolerated and improve the response rate and progression-free survival (PFS).
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Histologically or cytologically confirmed small cell lung cancer that has progressed on at least one line of prior platinum-based chemotherapy, given with or without anti-PD-(L)1 therapy.
Presence of measurable disease per RECIST 1.1 criteria
At least 18 years of age.
ECOG performance status ≤ 2
Disqualifiers
Prior or concurrent malignancy whose treatment or natural history has the potential to interfere with the safety or efficacy assessment of the investigational regimen. Patients with prior or concurrent malignancy that does NOT meet that definition (following discussion with the PI) are eligible for this trial.
Previous intolerance to irinotecan. Treatment with prior irinotecan is allowed as along as treatment was not discontinued for treatment related adverse events.
Currently receiving any other investigational agents.
Patients with untreated symptomatic brain metastases or with clinically evident CNS hemorrhage. Patients with treated brain metastases are allowed if post-treatment brain imaging after CNS-directed therapy shows no evidence of progression. Patients with asymptomatic, punctate brain metastases < 5 mm are allowed.
Trial design
Design model
Sequential
Treatments tested in this trial
Cirtuvivint
DrugCirtuvivint will be supplied by Biosplice.
Irinotecan
DrugIrinotecan is commercially available.
Treatment groups
42 Participants
are divided into 2 treatment groupsGroup A: Phase I: Irinotecan + CirtuvivintExperimental treatment 2 interventions
Group B: Phase II: Irinotecan + CirtuvivintExperimental treatment 2 interventions
Trial outcomes
Primary outcomes
1
Recommended Phase II dose (RP2D) (Phase I only)
\- The RP2D is defined as the dose level immediately below the dose level at which 2 patients of a cohort (of 2 to 6 patients) experience dose-limiting toxicity during the first cycle. Dose-limiting toxicities are defined in the protocol.
Time frame
Through completion of cycle 1 (cycle is 21 days) for all Phase I patients2
Objective response rate (ORR) per RECIST criteria (Phase II and RP2D only)
* ORR: Percentage of patients who have a complete response (CR) or partial response (PR). * Complete Response (CR): Disappearance of all target lesions. Disappearance of all non-target lesions and normalization of tumor marker level. All lymph nodes must be non-pathological in size (\<10 mm short axis). * Partial response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.
Time frame
Through completion of treatment (estimated to be 4 months)Secondary outcomes
1
Kaplan-Meier Estimate of Progression-Free Survival (PFS) (Phase II and RP2D only)
* PFS is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first. * Progressive Disease (PD): At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Appearance of one or more new lesions and/or unequivocal progression of existing non-target 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
Through completion of follow-up (estimated to be 10 months)2
Kaplan-Meier Estimate of Overall Survival (OS) (Phase II and RP2D only)
OS is defined as the length of time from start of treatment until date of death.
Time frame
Through completion of follow-up (estimated to be 10 months)Sponsors and contacts
Click on the lead sponsor to view all of their trials.
Washington University School of Medicine
Lead sponsor
Biosplice Therapeutics, Inc.
Collaborator
Source ClinicalTrials.gov