EGFR(V)-EDV-Dox for Brain Cancer

(CerebralEDV Trial)

No longer recruiting at 1 trial location

Overseen By Kelly Szajna, RN BSN

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Engeneic Pty Limited

Must not be taking: Anti-angiogenics, Anticoagulants

Disqualifiers: CNS bleeding, Coronary artery disease, HIV, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 9

Duration: 8 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety and tolerance of a new treatment called EGFR(V)-EDV-Dox, an experimental drug for recurring glioblastoma multiforme (GBM), an aggressive brain tumor. Researchers aim to determine the best dose for future studies and assess whether the treatment can effectively trigger an immune response against the tumor. Individuals with a confirmed diagnosis of recurrent GBM who have not responded to standard treatments might be suitable for this trial. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new drug.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, certain treatments like radiation, specific chemotherapies, and anticoagulation therapy must not have been received recently. It's best to discuss your current medications with the trial team.

Is there any evidence suggesting that EGFR(V)-EDV-Dox is likely to be safe for humans?

Research has shown that EGFR(V)-EDV-Dox, a new treatment under study for recurring glioblastoma multiforme (GBM), has been tested for safety in humans. In earlier studies, nausea, fever, and chills were the most common side effects, affecting only a few patients. These side effects were usually mild and resolved on their own. Other studies on similar treatments in animals showed only minor issues, such as slight weight loss. This suggests that EGFR(V)-EDV-Dox might be well-tolerated by people. However, as it remains in the early stages of testing, more information is needed to fully understand its safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Most treatments for recurrent glioblastoma multiforme (GBM) involve surgery, radiation, and chemotherapy. However, EGFR(V)-EDV-Dox is unique because it targets cancer cells using a bacterially derived vehicle to deliver the chemotherapy drug doxorubicin directly to tumor cells. This targeted approach aims to minimize damage to healthy cells, potentially reducing side effects compared to traditional chemotherapy. Researchers are excited about this method because it represents a more precise way to attack cancer cells, which could lead to better outcomes for patients with recurrent GBM.

What evidence suggests that EGFR(V)-EDV-Dox might be an effective treatment for recurrent glioblastoma multiforme?

Research has shown that EGFR inhibitors, such as the EGFR(V)-EDV-Dox treatment studied in this trial, improve response rates and control disease in other advanced cancers. Past studies demonstrated that these inhibitors help patients live longer without cancer progression. Early results suggest that combining nanotechnology with doxorubicin in EGFR(V)-EDV-Dox is well tolerated by patients with recurring glioblastoma multiforme (GBM). Although human studies have provided limited data, this treatment aims to deliver doxorubicin directly to the tumor by targeting specific cancer cell receptors, potentially increasing its effectiveness. The goal is for this targeted method to lead to better treatment outcomes for those with recurring GBM. ^{1 2 3 5 6}

Who Is on the Research Team?

Stuart A Grossman, M.D.

Principal Investigator

Johns Hopkins University

Himanshu Brahmbhatt, Ph. D

Principal Investigator

Engeneic Pty Limited

Gary L Gallia, M.D., Ph.D

Principal Investigator

Johns Hopkins University

Jennifer MacDiarmid, Ph.D

Principal Investigator

Engeneic Pty Limited

Are You a Good Fit for This Trial?

Inclusion Criteria

Karnofsky Performance Status (KPS) ≥ 60%.

Life expectancy ≥ 3 months.

Pathologically documented, and definitively diagnosed recurrent World Health Organization (WHO) Grade IV astrocytoma (GBM).

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive EGFR(V)-EDV-Dox weekly for 7 weeks via IV infusion, followed by radiological evaluation at week 8

8 weeks

8 visits (in-person)

Safety Follow-up

A safety follow-up visit is performed 30 (+5) days after the last dose of drug

5 weeks

1 visit (in-person)

Long-term Follow-up

Participants are monitored approximately every 1 month for 12 months, then every 2-3 months for survival

12 months

What Are the Treatments Tested in This Trial?

Interventions

• EGFR(V)-EDV-Dox

How Is the Trial Designed?

Group I: EGFR(V)-EDV-Dox Experimental Treatment 1 Intervention

EGFR(V)-EDV-Dox administered via 20 minute intravenous infusion once a week for seven weeks (1 Cycle). Subjects will receive one of two dose levels: 5 x 10\^9 or 8 x 10\^9. All subjects will undergo an adapted dose escalation regime in the first cycle of treatment. For subsequent cycles all doses will be administered at full strength (5x10\^9 or 8x10\^9 EGFR(V)-EDV-Dox). Subjects may receive further cycles of treatment if the tumor remains stable or is responding, and/or they are deriving clinical benefit from the therapy and are tolerating treatment.

Who Is Running the Clinical Trial?

Engeneic Pty Limited

Lead Sponsor

Trials

2

Recruited

30+

Johns Hopkins University

Collaborator

Trials

2,366

Recruited

15,160,000+

Published Research Related to This Trial

Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) significantly enhance progression-free and overall survival in patients with non-small cell lung cancer (NSCLC) who have activating mutations in the EGFR gene.

Despite their efficacy, EGFR-TKIs can cause several adverse events, such as diarrhea, liver toxicity, and skin issues, which can negatively impact patients' quality of life and adherence to treatment; therefore, managing these side effects is crucial for effective therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of EGFR-TKIs for EGFR mutation-positive non-small cell lung cancer. Zhou, JY., Liu, SY., Wu, YL.[2021]

In the Phase III RELAY trial, the combination of ramucirumab and erlotinib (RAM + ERL) significantly improved progression-free survival (PFS) in European and US patients with EGFR mutation-positive non-small cell lung cancer (NSCLC), with a median PFS of 20.6 months compared to 10.9 months for the placebo group.

The safety profile of RAM + ERL was consistent with the overall population, with hypertension being the most common severe side effect, indicating that ramucirumab is a safe and effective addition to standard EGFR-TKI therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

RELAY, ramucirumab plus erlotinib versus placebo plus erlotinib in patients with untreated, EGFR-mutated, metastatic non-small cell lung cancer: Europe/United States subset analysis. Ponce Aix, S., Novello, S., Garon, EB., et al.[2023]

EGFR inhibitors significantly improve objective response rates (ORR), disease control rates (DCR), and progression-free survival (PFS) in advanced non-small cell lung cancer patients with EGFR mutations compared to non-targeted chemotherapy, based on a review of 21 studies involving 4,250 patients.

Despite the improved response and control rates with EGFR inhibitors, overall survival (OS) did not show significant differences compared to non-targeted chemotherapy or older EGFR inhibitors, indicating that better short-term outcomes do not necessarily translate to longer survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of EGFR Inhibitors in the Treatment of EGFRPositive NSCLC Patients: A Meta-Analysis. Dang, A., Dang, S., Vallish, BN.[2021]

Targeting the epidermal growth factor receptor (EGFR) is a promising strategy in cancer therapy, as it plays a crucial role in processes like cancer cell growth and metastasis, with several anti-EGFR drugs currently in advanced clinical development.

Cetuximab and gefitinib are two key anti-EGFR drugs that have shown efficacy in treating specific types of cancer, such as advanced colorectal cancer and chemoresistant non-small cell lung cancer, respectively, highlighting their potential in improving patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Epidermal growth factor receptor inhibitors in cancer treatment. Ciardiello, F.[2018]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT02766699

NCT02766699 | A Study to Evaluate the Safety, Tolerability ... The purpose of the Cerebral EDV study is to determine the safety and tolerability of EGFR(V)-EDV-Dox in order to establish the best dose level to be used in ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/26279503/

First in human nanotechnology doxorubicin delivery ... Our results demonstrate that (V)EDVDox, up to a dose of 5×10(9)(V)EDVDox weekly, is well tolerated in patients with recurrent GBM.

3. withpower.com withpower.com/trial/phase-1-astrocytoma-9-2016-11904

A Study to Evaluate the Safety, Tolerability and ... EGFR inhibitors significantly improve objective response rates (ORR), disease control rates (DCR), and progression-free survival (PFS) in advanced non-small ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5961011/

EGFR heterogeneity and implications for therapeutic ... While these tumors responded to treatment with cetuximab, treatment with the anti-angiogenic agent bevacizumab did not affect tumor growth (unpublished data).

5. sciencedirect.com sciencedirect.com/science/article/pii/S1535610820300908

A Pathway Elicited by Tumor-Targeted, Cytotoxic Drug- ... Ep-EDV-682 treatment could not elicit an increase in immune cell populations as seen in non-depleted tumors and even exhibited a significant ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7763629/

Nanodelivery Systems Targeting Epidermal Growth Factor ... Many researchers also reported significant limitations such as low solubility, poor oral bioavailability, and severe adverse effects in the ...