LUNA18 for Solid Tumors
Recruiting in Palo Alto (17 mi)
+18 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Recruiting
Sponsor: Chugai Pharmaceutical
Disqualifiers: Cardiovascular disease, CNS malignancy, ILD, others
No Placebo Group
Trial Summary
What is the purpose of this trial?This trial is testing a new drug called LUNA18 to see if it can help treat advanced or spreading cancers. Researchers will look at how the drug moves through and affects the body, and whether it can help control or reduce tumors. The study includes patients whose cancer is difficult to treat with standard therapies.
Do I need to stop my current medications for the trial?
The trial protocol does not specify whether you need to stop taking your current medications.
What data supports the idea that LUNA18 for Solid Tumors is an effective treatment?
The available research does not provide specific data on the effectiveness of LUNA18 for Solid Tumors. The studies mentioned focus on other treatments and conditions, such as breast cancer and lung cancer, and do not include information about LUNA18. Therefore, there is no direct evidence from the provided information to support the effectiveness of LUNA18 for Solid Tumors.
12345What safety data is available for LUNA18 treatment?
The safety data for LUNA18, which may be related to Aurora kinase inhibitors like MLN8237 (alisertib) and MK-0457, includes common side effects such as febrile neutropenia, stomatitis, gastrointestinal toxicity, hypertension, and fatigue. These side effects have been observed in clinical trials involving Aurora kinase inhibitors for advanced solid tumors. Specific studies, such as the Phase I study of MLN8237, evaluated safety, pharmacokinetics, and dose-limiting toxicities in patients with advanced solid tumors.
678910Is the drug LUNA18 a promising treatment for solid tumors?
Yes, LUNA18 is a promising treatment for solid tumors. It has shown strong anti-tumor effects in animal studies, including reducing tumor growth and spreading. It also tends to stay in the tumor area, which could make it more effective.
1112131415Eligibility Criteria
Adults over 18 with advanced solid tumors not responding to standard treatments can join. They must be relatively healthy (ECOG status of 0 or 1) and have RAS mutation-positive tumors that are measurable. Those with serious heart conditions, uncontrolled diseases, lung complications like ILD, brain cancer, or active brain metastases needing treatment cannot participate.Inclusion Criteria
I am 18 years old or older.
My cancer is advanced, cannot be cured with surgery, and standard treatments haven't worked or I can't tolerate them.
I am fully active or can carry out light work.
+2 more
Exclusion Criteria
I do not have any severe, uncontrolled illnesses like heart, lung, or kidney diseases.
I do not have serious heart problems like recent heart attacks or unstable heart rhythms.
I have a brain tumor or cancer spread to my brain that needs treatment.
+1 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Dose Escalation
Patients receive LUNA18 capsule(s) at escalated doses to determine safety and tolerability
6-9 days for Cycle 0, 28 days for Cycle 1
Cohort Expansion
Patients receive LUNA18 capsule(s) at the recommended dose, alone or in combination with cetuximab
Up to approximately 43 months
Follow-up
Participants are monitored for safety and effectiveness after treatment
4 weeks
Participant Groups
The study is testing LUNA18's safety and effectiveness alone or with other cancer drugs in patients with advanced solid tumors. It's a Phase 1 trial where doses increase gradually to find the right balance between safety and potential benefits.
6Treatment groups
Experimental Treatment
Group I: Dose finding part (Part D)Experimental Treatment2 Interventions
Patients will receive LUNA18 capsule(s) in combination with cetuximab at finding doses
Group II: Dose escalation part (Part A)Experimental Treatment1 Intervention
Patients will receive LUNA18 capsule(s) at escalated doses
Group III: Cohort expansion part (Part E)Experimental Treatment2 Interventions
Patients will receive LUNA18 capsule(s) in combination with cetuximab at the recommended dose
Group IV: Cohort expansion part (Part C)Experimental Treatment1 Intervention
Patients will receive LUNA18 capsule(s) at the recommended dose
Group V: Biomarker part (Part B)Experimental Treatment1 Intervention
Patients will receive LUNA18 capsule(s) at doses where the tolerability is confirmed in Part A
Group VI: Backfill part (Part AA)Experimental Treatment1 Intervention
Patients will receive LUNA18 capsule(s) at doses where the tolerability is confirmed in Part A
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
University of California - DavisDavis, CA
Beth Israel DeaconessBoston, MA
Dana-Farber Cancer InstituteBoston, MA
Barbara Ann Karmanos Cancer InstituteDetroit, MI
More Trial Locations
Loading ...
Who Is Running the Clinical Trial?
Chugai PharmaceuticalLead Sponsor
References
An appraisal of FDA approvals for adult solid tumours in 2017-2021: has the eagle landed? [2022]In 2016, the then US President Barack Obama announced the Cancer Moonshot with a view to making 10 years' worth of progress in cancer prevention, diagnosis and treatment in only 5 years. This Perspective evaluates the FDA approvals of therapeutic agents for use in solid tumour oncology for the period 2017-2021 against the aspirations of the Cancer Moonshot. In the past 5 years, the FDA issued an unprecedented 161 new approvals of therapeutic agents for various indications in adult patients with solid tumours. However, less than a third (27%) of the newly approved medicines are supported by unequivocal evidence of an overall survival benefit; most are supported by positive signals from surrogate end points. Herein, the European Society for Medical Oncology Magnitude of Clinical Benefit Scale version 1.1 was used to evaluate the clinical value of the therapies granted FDA approval during the period 2017-2021. The results of this appraisal indicate a low level of clinical benefit for a substantial proportion (~20%) of the new indications, with most (~44%) providing intermediate benefit. The data suggest that, beyond increases in the sheer quantity of approvals, considerable improvement in the quality of the approved treatments is required to more confidently ensure that the clinical benefits are real and substantial enough to clearly justify the risks to patients.
Overall response rate, progression-free survival, and overall survival with targeted and standard therapies in advanced non-small-cell lung cancer: US Food and Drug Administration trial-level and patient-level analyses. [2022]To conduct analyses exploring trial-level and patient-level associations between overall response rate (ORR), progression-free survival (PFS), and overall survival (OS) in advanced non-small-cell lung cancer (NSCLC) trials.
Oncotype DX recurrence score implications for disparities in chemotherapy and breast cancer mortality in Georgia. [2023]Among women diagnosed with stage I-IIIa, node-negative, hormone receptor (HR)-positive breast cancer (BC), Oncotype DX recurrence scores (ODX RS) inform chemotherapy treatment decisions. Differences in recurrence scores or testing may contribute to racial disparities in BC mortality among women with HR+ tumors. We identified 12,081 non-Hispanic White (NHW) and non-Hispanic Black (NHB) BC patients in Georgia (2010-2014), eligible to receive an ODX RS. Logistic regression was used to estimate the odds of chemotherapy receipt by race and ODX RS. Cox proportional hazard regression was used to calculate the hazard ratios (HRs) comparing BC mortality rates by race and recurrence score. Receipt of Oncotype testing was consistent between NHB and NHW women. Receipt of chemotherapy was generally comparable within strata of ODX RS-although NHB women with low scores were slightly more likely to receive chemotherapy (OR = 1.16, 95% CI 0.77, 1.75), and NHB women with high scores less likely to receive chemotherapy (OR = 0.77, 95% CI 0.48, 1.24), than NHW counterparts. NHB women with a low recurrence score had the largest hazard of BC mortality (HR = 2.47 95% CI 1.22, 4.99) compared to NHW women. Our data suggest that additional tumor heterogeneity, or other downstream treatment factors, not captured by ODX, may be drivers of racial disparities in HR+ BC.
Concordance of real-world versus conventional progression-free survival from a phase 3 trial of endocrine therapy as first-line treatment for metastatic breast cancer. [2020]There is growing interest in leveraging real-world data to complement knowledge gained from randomized clinical trials and inform the design of prospective randomized studies in oncology. The present study compared clinical outcomes in women with metastatic breast cancer who received letrozole as first-line monotherapy in oncology practices across the United States versus patients in the letrozole-alone cohort of the PALOMA-2 phase 3 trial. The real-world cohort (N = 107) was derived from de-identified patient data from the Flatiron Health electronic health record database. The clinical trial cohort (N = 222) comprised postmenopausal women in the letrozole-alone arm of PALOMA-2. Patients in the real-world cohort received letrozole monotherapy per labeling and clinical judgment; patients in PALOMA-2 received letrozole 2.5 mg/d, continuous. Real-world survival and response rates were based on evidence of disease burden curated from clinician notes, radiologic reports, and pathology reports available in the electronic health record. Progression-free survival and objective response rate in PALOMA-2 were based on Response Evaluation Criteria in Solid Tumors v1.1. Concordance of survival and response rates were retrospectively assessed using inverse probability of treatment weighting-adjusted Cox regression analysis. Inverse probability of treatment weighting-adjusted Cox regression results showed similar median progression-free survival in the real-world and PALOMA-2 cohorts (18.4 and 16.6 months, respectively): the hazard ratio using real-world data as reference was 1.04 (95% CI, 0.69-1.56). No significant difference was observed in response rates: 41.8% in the real-world cohort vs 39.4% in the PALOMA-2 cohort (odds ratio using real-world data as reference: 0.91 [95% CI, 0.57-1.44]). These findings indicate that data abstracted from electronic health records with proper quality controls can yield meaningful information on clinical outcomes. These data increase confidence in the use of real-world assessments of progression and response as efficacy endpoints. Trial registration NCT01740427; Funding: Pfizer.
Palbociclib and cetuximab compared with placebo and cetuximab in platinum-resistant, cetuximab-naïve, human papillomavirus-unrelated recurrent or metastatic head and neck squamous cell carcinoma: A double-blind, randomized, phase 2 trial. [2021]This study examined whether palbociclib and cetuximab prolonged overall survival (OS) versus placebo and cetuximab.
Phase I study of aurora A kinase inhibitor MLN8237 in advanced solid tumors: safety, pharmacokinetics, pharmacodynamics, and bioavailability of two oral formulations. [2021]This phase I study evaluated the safety, pharmacokinetics, pharmacodynamics, and efficacy of the investigational oral drug MLN8237 (alisertib), a small-molecule Aurora A kinase (AAK) inhibitor, in 87 adult patients with advanced solid tumors.
Aurora Kinase Inhibitors in Oncology Clinical Trials: Current State of the Progress. [2022]The Aurora kinase family of kinases (Aurora A, B, and C) are involved in multiple mitotic events, and aberrant expression of these kinases is associated with tumorigenesis. Aurora A and Aurora B are validated anticancer targets, and the development of Aurora kinase inhibitors has progressed from preclinical to clinical studies. A variety of Aurora A, B and pan-Aurora kinase inhibitors have entered the clinic. The main side effects include febrile neutropenia, stomatitis, gastrointestinal toxicity, hypertension, and fatigue. Responses including complete remissions have been described in diverse, advanced malignancies, most notably ovarian cancer and acute myelogenous leukemia. This review highlights the biologic rationale for Aurora kinase as a target, and clinical trials involving Aurora kinase inhibitors, with particular emphasis on published early phase studies, and the observed anti-tumor activity of these agents.
Phase I dose escalation study of MK-0457, a novel Aurora kinase inhibitor, in adult patients with advanced solid tumors. [2022]To assess the maximum-tolerated dose (MTD), dose-limiting toxicity (DLT), safety, and tolerability of the 24-h continuous intravenous (CIV) infusion of MK-0457, a novel pan-Aurora kinase inhibitor, in patients with advanced solid tumors and to determine the bioavailability of an oral dose of 100 mg MK-0457.
Phase 1 study of MLN8054, a selective inhibitor of Aurora A kinase in patients with advanced solid tumors. [2021]Aurora A kinase is critical in assembly and function of the mitotic spindle. It is overexpressed in various tumor types and implicated in oncogenesis and tumor progression. This trial evaluated the dose-limiting toxicities (DLTs) and maximum tolerated dose (MTD) of MLN8054, a selective small-molecule inhibitor of Aurora A kinase.
Early phase II trial of oral vorinostat in relapsed or refractory breast, colorectal, or non-small cell lung cancer. [2021]Vorinostat (Zolinza) is a histone deacetylase inhibitor that has demonstrated activity in patients with advanced solid tumors in phase I trials. A multicenter, open-label phase II trial of oral vorinostat 200, 300 or 400 mg bid for 14 days followed by a 7-day rest until disease progression or intolerable toxicity was conducted. Patients with measurable, relapsed or refractory breast or non-small cell lung cancer who had received > or = 1 prior therapy or colorectal cancer who had received > or = 2 prior therapies were eligible. The response rate, safety and tolerability were evaluated. Sixteen patients (median age, 62 years; median 5.5 prior therapies) were enrolled. Six patients received 400 mg bid, six received 300 mg bid and four received 200 mg bid (14 days/3 weeks). Dose-limiting toxicities (DLTs) at the 400 or 300 mg bid levels were anorexia, asthenia, nausea, thrombocytopenia, vomiting, and weight loss. No DLTs were observed at the 200 mg bid level. Disease stabilization was observed in eight patients, but there were no confirmed responses. The median TTP was 33.5 days. Eleven patients discontinued due to clinical adverse experiences (AEs). The most common drug-related AEs were anorexia (81%), fatigue (62%), nausea (62%), diarrhea (56%), vomiting (56%), thrombocytopenia (50%) and weight loss (50%). Drug-related AEs > or = grade 3 included thrombocytopenia (50%), anemia (12%), asthenia (12%) and nausea (12%). Vorinostat in a daily oral schedule for 14 days/3 weeks was tolerable at 200 mg bid only, and no responses were observed in this study. Most patients, however, had limited drug exposure which did not allow a reliable efficacy analysis.
Antitumor effects of 3-[p-(N,N-bis-(2'-chloroethyl)amino)-phenyl]-L- alanine conjugated with human immunoglobulin (K18). [2013]K18 (3-[p-(N,N-bis(2'-chloroethyl)amino)- phenyl]-L-alanine conjugated with human immunoglobulin) is a newly developed antitumor agent. LD50 values of K18 in animals were quite high, suggesting its low acute toxicity. This drug showed anti-tumorigenicity not only on an experimental animal tumor (Walker 256), but also on a human tumor transplantable into nude mice (RCC-13). A distribution study clarified the unique properties of K18 to accumulate and remain in the tumor site with a high rate.
Antitumor effect of K18 on metastatic models. [2013]K18 is a newly synthesized antitumor agent which is the conjugate form of human immunoglobulin with p-di (2-chloroethyl)-amino-L-phenylalamine (melphalan). The antitumor effect of K18 on two animal metastatic models was investigated: (a) Lewis lung carcinoma was transplanted into thigh muscle of mice, followed by the reaction of the primary lesion, or the tumor was transplanted through the tail vein: (b) a renal model was also created, where colon-26 was inoculated into the renal capsule of BALB/c mice. Oral administration of K18 resulted in the decrease in the number of nodules in the lung in the case of tumor transplantation through tail vein.
Transcription Factor SOX18 Promotes Clear Cell Renal Cell Carcinoma Progression and Alleviates Cabozantinib-Mediated Inhibitory Effects. [2020]The transcription factor SOX18, which was initially discovered as an activator of genetic transcription during embryogenesis, is now implicated in many diseases, including cancer, and is associated with the malignant tumor phenotype, angiogenesis, and lymphangiogenesis. However, the role of SOX18 in clear cell renal cell carcinoma (ccRCC) is not well understood. In the current study, SOX18 expression was evaluated in a 250 case-cohort of primary ccRCC tissues that included 103 cases of matched normal kidney tissues and 21 cases of metastatic tissues. Functional and mechanistic analyses were performed in cells that had SOX18 either overexpressed or silenced to evaluate the effects of SOX18 on cell function, the cellular response to cabozantinib, and SOX18-mediated molecular mechanisms. Our data revealed that upregulation and nuclear translocation of SOX18 promoted ccRCC carcinogenesis and metastasis. Elevated SOX18 expression was associated with advanced pathologic grades and TNM stages, as well as poor patient survival. SOX18 also regulated the cell cycle and the epithelial-mesenchymal transition to promote the malignant phenotype in ccRCC cells. The activation of EGF/EGFR and HGF/c-MET signaling in vitro and in vivo was induced by SOX18. Moreover, SOX18 activation bypassed the inhibitory effects of cabozantinib on cell proliferation, migration, and invasion. In conclusion, our data indicate that SOX18 may be a promising therapeutic target for ccRCC treatment.
Interleukin-6 upregulates SOX18 expression in osteosarcoma. [2022]SOX18 is a potential oncogene in osteosarcoma via controlling osteosarcoma cell proliferation and metastasis. Interleukin-6 (IL-6), a major activator of Janus kinase 2 (JAK2)/signal transducers and activators of transcription 3 (STAT3) signaling, plays an important role in the growth of carcinoma cells. The present study aims to investigate the correlation between IL-6 and SOX18 in osteosarcoma.
Heterogeneous expression and biological function of SOX18 in osteosaroma. [2018]Osteosaroma (OS) is a primary bone malignancy and is associated with high morbidity. Sex determining region Y-box 18 (SOX18) is identified overexpressed in OS. However, the molecular mechanism underlying the biological function of SOX18 in OS is still unclear. The aim of the current study was to determine the SOX18 expression in patients with OS and its effect on tumor cell malignant phenotypes. Our results showed that SOX18 was overexpressed in OS patients from both E-MEXP-3628 database and independent samples from our hospital and in OS cell lines. SOX18 silencing significantly induced G0-G1 phase cell cycle arrest and apoptosis and inhibited U-2OS cell migration and invasion and cell growth both in vitro and in vivo. However, SOX18 overexpression remarkably promoted 143B cell proliferation, migration and invasion and inhibited cell cycle arrest and apoptosis. The protein expression levels of p53, p21, Bax, Bcl-2, and Caspase-3 were also regulated by SOX18. Moreover, SOX18 was found negative correlated with the expression of HERC1, HER2, HERC3, HERC4, HERC5, and HERC6 in OS patients and in OS cells, with the most significant correlation detected in HERC2 expression, which was following found interacted with SOX18 in OS cells. Taken together, our results suggest that SOX18 is overexpressed in OS and plays an important role in proliferation, apoptosis, migration and invasion of OS cells, and may provide a novel and promising thera-peutic strategy for OS.