What side effects are associated with this type of intervention?

Common treatments for esophageal cancer, such as chemotherapy, immunotherapy, and radiation therapy, have a range of side effects. Chemotherapy agents like docetaxel, cisplatin, and fluorouracil can cause mucositis, myelosuppression, nausea, and neuropathy. Immunotherapy drugs, including pembrolizumab and nivolumab, may lead to immune-related adverse effects such as colitis, dermatitis, and endocrinopathies. Radiation therapy can result in esophagitis, fatigue, and skin reactions. These side effects vary in severity and frequency among patients.

What prior FDA approvals exist?

The FDA has approved several anti-cancer agents for the treatment of esophageal cancer, particularly for advanced stages. Notable approvals include pembrolizumab (Keytruda), an anti-PD-1 monoclonal antibody, for patients with recurrent locally advanced or metastatic squamous cell carcinoma (SCC) of the esophagus expressing high levels of PD-L1. Nivolumab (Opdivo), another anti-PD-1 monoclonal antibody, has also been approved for esophageal SCC, showing efficacy in patients who have progressed after prior chemotherapy. These immunotherapy agents are similar to VLS-1488 in their role as targeted treatments for advanced cancer.

What other types of research exist?

Promising novel alternatives to VLS-1488 for esophageal cancer patients include pembrolizumab, which has shown efficacy in PD-L1-positive advanced gastric or gastroesophageal junction cancer, and trastuzumab, which is used beyond progression in HER2-positive advanced gastric or gastroesophageal junction cancer. Additionally, the combination of carboplatin and etoposide with atezolizumab or durvalumab has shown improved survival outcomes in extensive-stage small cell lung cancer, which may be relevant for esophageal cancer treatment.

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VLS-1488 for Advanced Cancer

Phase 1 & 2

Recruiting

Research Sponsored by Volastra Therapeutics, Inc.

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

For Dose Escalation: No available therapeutic options to provide clinically meaningful benefits in specific tumor types

ECOG Performance Status ≤ 1

Must not have

Any clinically significant ascites or pleural effusions at time of enrollment, or any therapeutic paracentesis or thoracentesis within 28 days of planned first dose of study drug

Inability to comply with concomitant medication restrictions with respect to strong inhibitors and inducers of CYP3A, and clinical inhibitors of MDR1 (P-gp) and BCRP

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 5 years

Awards & highlights

No Placebo-Only Group

Summary

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.

Who is the study for?

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.

What is being tested?

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.

What are the potential side effects?

As this is a first-in-human study for VLS-1488, specific side effects are not yet known but may include typical reactions related to cancer drugs such as nausea, fatigue, allergic reactions or more serious complications depending on individual patient responses.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I have no other treatment options that would significantly help my cancer.

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I am fully active or can carry out light work.

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I can swallow pills without needing to crush or dissolve them.

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I am 18 years old or older.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I haven't had fluid drained from my abdomen or chest in the last 28 days.

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I can avoid medications that strongly affect certain liver enzymes and drug transporters.

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My cancer has specific genetic mutations or is known to mutate quickly.

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My cancer has spread to my brain or spinal cord.

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I have been treated with a KIF18A inhibitor before.

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I haven't had recent severe heart issues or a heart function below normal.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 5 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 5 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 5 years for reporting.

Treatment Details

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

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.

0 / 10Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for esophageal cancer include chemotherapy, radiation therapy, and immunotherapy. Chemotherapy targets rapidly dividing cancer cells to disrupt their growth and replication. Radiation therapy uses high-energy rays to damage the DNA of cancer cells, leading to their death. Immunotherapy, such as pembrolizumab and nivolumab, enhances the immune system's ability to detect and destroy cancer cells by inhibiting checkpoints like PD-1/PD-L1. These mechanisms are important for esophageal cancer patients as they help tailor treatment plans to effectively target the cancer while considering the patient's overall health and specific cancer characteristics.

Minimally Invasive Versus Open Esophageal Resection: Three-year Follow-up of the Previously Reported Randomized Controlled Trial: the TIME Trial.