VLS-1488 for Advanced Cancer
Recruiting in Palo Alto (17 mi)
+12 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1 & 2
Recruiting
Sponsor: Volastra Therapeutics, Inc.
Must not be taking: CYP3A inhibitors, MDR1 inhibitors
Disqualifiers: CNS metastases, Cardiac issues, others
No Placebo Group
Approved in 1 jurisdiction
Trial Summary
What is the purpose of this trial?This trial tests VLS-1488, a new drug for advanced cancers, to find the safest and most effective dose. It targets patients needing new treatment options and checks how the drug interacts with other medications and food.
Will I have to stop taking my current medications?
The trial protocol does not specify if you must stop taking your current medications, but it mentions restrictions on certain medications that affect liver enzymes and drug transporters. It's best to discuss your current medications with the trial team to see if any adjustments are needed.
What is known about the safety of VLS-1488 or similar treatments in humans?
Vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors, which may be similar to VLS-1488, have been associated with risks like bleeding, heart issues, and other serious side effects. However, studies show that these treatments do not significantly increase the risk of fatal adverse events compared to other treatments.
12345How is the drug VLS-1488 different from other treatments for advanced cancer?
VLS-1488 is unique because it may act as a vascular disrupting agent (VDA), which means it targets and disrupts the blood vessels that supply the tumor, potentially leading to tumor necrosis (tissue death) and inhibiting tumor growth. This mechanism is different from standard chemotherapy, which typically targets cancer cells directly.
678910Eligibility Criteria
This trial is for adults with advanced cancers who've already tried standard treatments. They should be able to perform daily activities with minimal assistance (ECOG ≤ 1), have measurable disease, and take pills without changing them. Not eligible if they have certain genetic mutations, brain metastases, previous KIF18A inhibitor treatment, or recent serious heart issues.Inclusion Criteria
I have at least one tumor that can be measured on a CT scan or MRI.
I have no other treatment options that would significantly help my cancer.
I am fully active or can carry out light work.
+3 more
Exclusion Criteria
I haven't had fluid drained from my abdomen or chest in the last 28 days.
I can avoid medications that strongly affect certain liver enzymes and drug transporters.
I have not had a bowel blockage or gut tear in the last 6 months.
+4 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Dose Escalation
Examine the safety and tolerability of VLS-1488 in different solid tumor types at various dose levels to identify the Maximum Tolerated Dose (MTD)
28-day cycles
Dose Expansion
Examine the safety, tolerability, Drug Drug Interaction (DDI) risk, Food Effect (FE), and preliminary efficacy of VLS-1488 in different tumor types and/or dose levels
28-day cycles
Follow-up
Participants are monitored for safety and effectiveness after treatment
4 weeks
Participant Groups
The study tests VLS-1488's safety and early effectiveness in patients with various advanced cancers. It includes two parts: dose escalation to find the right amount of drug and dose expansion to see how well it works at that dose.
4Treatment groups
Experimental Treatment
Group I: Dose Expansion: Exploration CohortsExperimental Treatment1 Intervention
Subjects with a selected single tumor type will be randomized 1:1 into Exploration Cohorts at two or more dose levels of interest. A subset of subjects will have additional assessments to examine the potential for VLS-1488 to interact with other drugs and the effect of food on VLS-1488 absorption.
Group II: Dose Expansion: Development CohortsExperimental Treatment1 Intervention
Subjects with other tumor types will be enrolled at a single dose level of interest. These Development Cohorts will be utilized to examine the preliminary efficacy of VLS-1488 in various tumor types.
Group III: Dose Escalation: Dose Escalation CohortsExperimental Treatment1 Intervention
Subjects will be enrolled at various doses and/or schedules of VLS-1488. These Dose Escalation Cohorts will be utilized to identify the MTD and to select dose levels for Dose Expansion.
Group IV: Dose Escalation: Backfill CohortsExperimental Treatment1 Intervention
Additional subjects may be enrolled at any dose level that does not meet de-escalation or elimination rules per the BOIN design. These Backfill Cohorts will be utilized to build additional data to support selection of doses and/or tumor types for further study in Dose Expansion.
VLS-1488 is already approved in United States for the following indications:
🇺🇸 Approved in United States as VLS-1488 for:
- None approved yet; Fast Track designation for platinum-resistant high-grade serous ovarian cancer
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
University of Southern CaliforniaLos Angeles, CA
The Christ HospitalCincinatti, OH
Yale Cancer CenterNew Haven, CT
Women & Infants HospitalProvidence, RI
More Trial Locations
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Who Is Running the Clinical Trial?
Volastra Therapeutics, Inc.Lead Sponsor
References
Safety profile and tolerability of antiangiogenic agents in non-small-cell lung cancer. [2022]Recent advances in understanding the importance of angiogenesis to tumor growth and distant metastasis has driven the development of antiangiogenic therapies for the treatment of non-small-cell lung cancer (NSCLC). The anti-vascular endothelial growth factor (VEGF) monoclonal antibody, bevacizumab, is the only US Food and Drug Administration-approved antiangiogenic agent for advanced NSCLC. Accumulated safety data with bevacizumab in NSCLC shows that patients are at risk for hemorrhage, venous thromboembolism, hypertension, and proteinuria. Investigational agents that target VEGF via a different mechanism (such as aflibercept [VEGF Trap]) or simultaneously inhibit multiple molecular pathways involved in angiogenesis (ie, multitargeted tyrosine kinase inhibitors [TKIs]) and vascular disrupting agents (VDAs) that target existing tumor vasculature are in various stages of clinical development for NSCLC, and safety profiles are emerging for these classes of agents. This review describes the molecular rationale for targeting angiogenic pathways in anticancer therapy and summarizes safety and tolerability data from clinical trials of bevacizumab or aflibercept in combination with chemotherapy and the investigational TKIs and VDAs in patients who have advanced NSCLC.
Clinical Safety of Combined Targeted and Viscum album L. Therapy in Oncological Patients. [2020]Background: Despite improvement of tumor response rates, targeted therapy may induce toxicities in cancer patients. Recent studies indicate amelioration of adverse events (AEs) by add-on mistletoe (Viscum album L., VA) in standard oncological treatment. The primary objective of this multicenter observational study was to determine the safety profile of targeted and add-on VA therapy compared to targeted therapy alone. Methods: Demographic and medical data were retrieved from the Network Oncology registry. Allocation to either control (targeted therapy) or combinational group (targeted/add-on VA) was performed. Safety-associated variables were evaluated by adjusted multivariable analyses. Results: The median age of the study population (n = 310) at first diagnosis was 59 years; 67.4% were female. In total, 126 patients (40.6%) were in the control and 184 patients (59.4%) in the combination group. Significant differences were observed between both groups with respect to overall AE frequency (χ² = 4.1, p = 0.04) and to discontinuation of standard oncological treatment (χ² = 4.8, p = 0.03) with lower rates in the combinational group (20.1%, 35% respectively) compared to control (30.2%, 60.5%, respectively). Addition of VA to targeted therapy significantly reduced the probability of oncological treatment discontinuation by 70% (Odds ratio (OR) 0.30, p = 0.02). Conclusions: Our results indicate a highly significant reduction of AE-induced treatment discontinuation in all-stage cancer patients when treated with VA in addition to targeted therapy.
Are VEGFR-TKIs effective or safe for patients with advanced non-small cell lung cancer? [2022]Vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKIs) might be new therapeutic strategies for advanced non-small cell lung cancer (NSCLC). Here a total of 12,520 patients from 23 randomized controlled trials (RCTs) were enrolled to evaluate the efficacy and safety of VEGFR-TKIs quantitatively in advanced NSCLC. Compared with non-VEGFR-TKIs, VEGFR-TKIs regimen significantly improved progression-free survival (PFS) [hazard ratio (HR): 0.839, 95% confidence interval (CI): 0.805-0.874, P
Incidence and Risk of Fatal Adverse Events in Cancer Patients Treated With Vascular Endothelial Growth Factor Receptor 2-Targeted Agents: A Meta-Analysis With Trial Sequential Analysis of Randomized Controlled Trials. [2020]Background/Aim: Agents targeting vascular endothelial growth factor (VEGF) pathway have dramatically improved the outlook of cancer treatment. Meanwhile, it is well-known that they are associated with increases in the risk of fatal adverse events (FAEs). Vascular endothelial growth factor receptor 2 (VEGFR2)-targeted drugs have been approved for the treatment of several malignancies. However, little is known regarding the FAEs induced by VEGFR2-targeted agents across different tumor types and treatment regimens. Methods: We searched PubMed and Embase database from January 1966 to April 2018 for randomized controlled trials (RCTs) to calculate the incidence and relative risks (RRs) of FAE. Results: Seventeen RCTs involving 6,982 subjects with solid tumors were included in this study. The overall incidence of FAEs associated with VEGFR2-targeted agents was 1.7% (95% CI: 0.9-2.4%). Compared with controls, the administration of VEGFR2-targeted agents did not increase the risk of FAEs (RR, 1.29; 95% CI: 0.90-1.86). No significant association was found between FAE and VEGFR2-targeted agents in subgroup analyses based on tumor type, treatment strategy, clinical phase, masking method, median treatment duration, and approval status. Additionally, FAEs occurred in the major organ systems dispersedly. Trial sequential analysis revealed that our results are solid and further studies are unlikely to change this. Conclusions: VEGFR2-targeted agents were not associated with an increased risk of FAEs.
Meta-analysis of randomized controlled trials for the incidence and risk of treatment-related mortality in patients with cancer treated with vascular endothelial growth factor tyrosine kinase inhibitors. [2022]Vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKIs) have become the cornerstone in the treatment of several malignancies. These drugs have also been associated with an increase in the risk of potentially life-threatening adverse events, such as arterial thrombotic events, bleeding, congestive heart failure, and others. We performed an up-to-date meta-analysis to determine the risk of fatal adverse events (FAEs) in patients with cancer treated with VEGFR TKIs.
Clinical trials of vascular disrupting agents in advanced non--small-cell lung cancer. [2012]Tumor vascular disrupting agents (VDAs), such as the flavonoid compound ASA404 and the tubulin-binding compound combretastatin, selectively disrupt established tumor blood vessels, inhibit tumor blood flow, and induce extensive necrosis at the core of solid tumors. A rationale for combining tumor VDAs with standard chemotherapy for treating advanced non-small-cell lung cancer (NSCLC) includes their complementary actions on different spatial regions of solid tumors and their additive or synergistic preclinical activity in animal models of lung cancer. A randomized, phase II, multicenter, open-label trial with a single-arm extension phase evaluated outcomes in a total of 104 patients (> 18 years of age) with histologically confirmed stage IIIb or stage IV, previously untreated NSCLC that in this trial was treated with ASA404 plus standard chemotherapy vs. standard chemotherapy alone. Adding ASA404 to standard chemotherapy numerically improved tumor response, time to disease progression, and overall survival in this phase II trial, without significantly increasing the incidence or severity of side effects. Other randomized phase II and phase III clinical trials of ASA404 and combretastatin combined with standard chemotherapy in advanced NSCLC are currently ongoing or will be reported shortly.
A randomized phase II efficacy and safety study of vandetanib (ZD6474) in combination with bicalutamide versus bicalutamide alone in patients with chemotherapy naïve castration-resistant prostate cancer. [2022]To investigate the efficacy and safety of combining vandetanib, an orally available multi-targeted tyrosine kinase inhibitor of vascular endothelial growth factor receptor-2 (VEGFR-2) and epidermal growth factor receptor (EGFR), with bicalutamide in patients with metastatic castration-resistant prostate cancer (mCRPC).
Safety and pharmacokinetics of motesanib in combination with gemcitabine and erlotinib for the treatment of solid tumors: a phase 1b study. [2022]This phase 1b study assessed the maximum tolerated dose (MTD), safety, and pharmacokinetics of motesanib (a small-molecule antagonist of VEGF receptors 1, 2, and 3; platelet-derived growth factor receptor; and Kit) administered once daily (QD) or twice daily (BID) in combination with erlotinib and gemcitabine in patients with solid tumors.
Motesanib, or open-label bevacizumab, in combination with paclitaxel, as first-line treatment for HER2-negative locally recurrent or metastatic breast cancer: a phase 2, randomised, double-blind, placebo-controlled study. [2022]Vascular endothelial growth factor (VEGF) has a crucial role in angiogenesis, and is a valid target in metastatic breast cancer. Motesanib is an investigational oral inhibitor of VEGF receptors. We aimed to determine whether treatment with motesanib plus paclitaxel is better than placebo plus paclitaxel in patients with HER2-negative locally recurrent or metastatic breast cancer.
A phase I and pharmacokinetic study of daily oral cediranib, an inhibitor of vascular endothelial growth factor tyrosine kinases, in combination with cisplatin and gemcitabine in patients with advanced non-small cell lung cancer: a study of the National Cancer Institute of Canada Clinical Trials Group. [2022]Cediranib, a potent vascular endothelial growth factor inhibitor, demonstrated broad pre-clinical anti-tumour activity. This study evaluated escalating cediranib doses with combination chemotherapy in advanced non-small cell lung cancer patients.