ERC1671 + GM-CSF + Cyclophosphamide for Glioblastoma

Not currently recruiting at 2 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Epitopoietic Research Corporation

Must not be taking: Immunosuppressants, Bevacizumab

Disqualifiers: Metastatic disease, Active infection, Uncontrolled hypertension, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 8

Duration: 28 days per cycle, repeated until disease progression or intolerance

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of treatments to determine if they outperform standard treatment in individuals with glioblastoma, a type of brain cancer. The treatment mix includes ERC1671, GM-CSF (which boosts the immune system), Cyclophosphamide (a chemotherapy drug), and Bevacizumab, a common cancer treatment. The trial compares this combination to a placebo group, with both groups also receiving Bevacizumab. It suits those whose glioblastoma has returned or worsened after initial treatments like surgery and radiation and who have not yet received Bevacizumab. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it mentions that patients taking temozolomide can start the study treatment 23 days after their last dose. For other chemotherapy drugs, treatment can start as long as side effects are mild. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the combination of ERC1671, GM-CSF, and cyclophosphamide is generally well-tolerated. In earlier studies, patients who received this combination with bevacizumab lived longer and experienced only a few more side effects than those who received only bevacizumab.

ERC1671 is designed to strengthen the immune system, and studies have not identified any major safety issues with it. Cyclophosphamide and GM-CSF are also used in other treatments, so their safety is well understood. Overall, early results suggest this treatment combination is safe, with some patients experiencing significant long-term benefits. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of ERC1671, GM-CSF, and Cyclophosphamide for treating glioblastoma because it introduces an innovative approach compared to the standard treatments like temozolomide and radiation. Unlike typical therapies that primarily focus on targeting tumor cells directly, ERC1671 is derived from tumor cells and aims to stimulate the body's immune system to recognize and attack the cancer. This immunotherapy-based strategy, combined with GM-CSF which boosts immune response, and Cyclophosphamide which enhances the effect by modulating the immune environment, offers a potentially more targeted and effective way to combat this aggressive brain cancer. Additionally, the use of bevacizumab or its biosimilars complements this regimen by inhibiting blood vessel growth in tumors, which might enhance the overall efficacy of the treatment.

What evidence suggests that this trial's treatments could be effective for glioblastoma?

This trial will compare two treatment approaches for recurrent glioblastoma. One group will receive a combination of ERC1671, GM-CSF, and cyclophosphamide with bevacizumab. Studies have shown that this combination can significantly extend the lives of patients with recurrent glioblastoma. Specifically, research indicates that all patients treated with this combination were alive six months after starting treatment. After 12 months, these patients still had better survival rates compared to those who only received bevacizumab. Cyclophosphamide is generally safe, though it can lower white blood cell counts. This combination treatment is under study because it aims to boost the immune system's ability to fight the tumor. The control group will receive placebo injections and pills alongside bevacizumab or its biosimilar. ^{1 2 4 6 7}

Who Is on the Research Team?

Daniela A. Bota, MD, PhD

Principal Investigator

University of California, Irvine

Are You a Good Fit for This Trial?

This trial is for adults over 18 with glioblastoma or gliosarcoma who are experiencing their first or second relapse. They must have had prior surgery, radiation, and chemotherapy with temozolomide, be in good physical condition (KPS ≥ 70%), and have a life expectancy of more than 12 weeks. Participants should not currently have severe treatment-related side effects except hair loss and certain blood conditions.

Inclusion Criteria

MRI record must show specific timing in relation to prior treatments

Life expectancy > 12 weeks

Signed informed consent approved by the Institutional Review Board

Exclusion Criteria

I haven't had any major abdominal issues like fistula, perforation, or abscess in the last 6 months.

I have had a heart problem recently.

I haven't taken immunosuppressive drugs in the last 2 weeks, except for dexamethasone for brain swelling.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive ERC1671, GM-CSF, and cyclophosphamide in combination with bevacizumab or placebo controls in 28-day cycles

28 days per cycle, repeated until disease progression or intolerance

Every 2 weeks for bevacizumab administration

Follow-up

Participants are monitored for safety, effectiveness, and immune response after treatment

12 months

Every 6 weeks for radiographic assessment

What Are the Treatments Tested in This Trial?

Interventions

• Cyclophosphamide
• ERC1671
• GM-CSF

Trial Overview The study tests if ERC1671 combined with GM-CSF and Cyclophosphamide improves outcomes when added to Bevacizumab compared to placebo injections/pills plus Bevacizumab in patients with recurrent/progressive glioblastoma multiforme that haven't been treated with Bevacizumab before.

How Is the Trial Designed?

Group I: (ERC1671/GM-CSF/Cyclophosphamide)+bevacizumab/bevacizumab biosimilar Experimental Treatment 4 Interventions

ERC1671 and GM-CSF will be intradermally administered, while cyclophosphamide is orally administered. GM-CSF dose is 500mcg fixed dose and cyclophosphamide dose is 50 mg/day. Bevacizumab or approved bevacizumab biosimilars are administered as standard of care at 10 mg/kg every 2 weeks. The treatment will be repeated every 28 days until progression of disease or intolerance.

Group II: (Placebo Injection/Placebo Pill) +Bevacizumab/bevacizumab biosimilar Placebo Group 3 Interventions

The control group will have the same study schedule except that the patients will be receiving the Oral Control on the Cyclophosphamide treatment days and the Injectable control on the GM-CSF + ERC1671 treatment days. The control group will receive bevacizumab or approved bevacizumab biosimilar just as the active treatment group above. The treatment will be repeated every 28 days until progression of disease or intolerance.

Cyclophosphamide is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as Cytoxan for:

• Breast cancer
• Ovarian cancer
• Multiple myeloma
• Leukemia
• Lymphoma
• Rheumatoid arthritis

Approved in European Union as Endoxan for:

• Breast cancer
• Ovarian cancer
• Multiple myeloma
• Leukemia
• Lymphoma
• Rheumatoid arthritis

Approved in Canada as Neosar for:

• Breast cancer
• Ovarian cancer
• Multiple myeloma
• Leukemia
• Lymphoma
• Rheumatoid arthritis

Approved in Japan as Endoxan for:

• Breast cancer
• Ovarian cancer
• Multiple myeloma
• Leukemia
• Lymphoma

Who Is Running the Clinical Trial?

Epitopoietic Research Corporation

Lead Sponsor

Trials

2

Recruited

110+

University of California, Irvine

Collaborator

Trials

580

Recruited

4,943,000+

Published Research Related to This Trial

A high-dose intensity regimen of cyclophosphamide combined with GM-CSF was tested in 23 children with brain tumors, showing partial responses in 5 out of 6 patients with primitive neuroectodermal tumors (PNET), but no effectiveness against malignant glioma.

The treatment resulted in a manageable safety profile, with a short duration of severe neutropenia, although fever during neutropenia was common, occurring in 54 out of 83 treatment cycles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I and II trial of dose-intensified cyclophosphamide and GM-CSF in pediatric malignant brain tumors. Abrahamsen, TG., Lange, BJ., Packer, RJ., et al.[2020]

In a study involving 35 patients (18 receiving GM-CSF and 17 controls), GM-CSF did not enhance T cell or natural killer cell recovery after allogeneic stem cell transplantation, contrary to expectations.

However, GM-CSF administration improved dendritic cell reconstitution in patients undergoing autologous stem cell transplantation, suggesting its benefits may vary based on the type of transplant.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Granulocyte-macrophage colony-stimulating factor increases the proportion of circulating dendritic cells after autologous but not after allogeneic hematopoietic stem cell transplantation. Eksioglu, EA., Kielbasa, J., Eisen, S., et al.[2018]

A case report described an adverse reaction to sargramostim (rhu GM-CSF) involving symptoms like itching, hives, and throat tightness, highlighting the potential for allergic reactions to this treatment.

Prick skin testing showed that the patient was sensitized to sargramostim but not to filgrastim (rhu G-CSF), suggesting that skin testing could help identify patients at risk for allergic reactions to GM-CSF therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immediate hypersensitivity to human recombinant granulocyte-macrophage colony-stimulating factor associated with a positive prick skin test reaction. Engler, RJ., Weiss, RB.[2017]

Mecapegfilgrastim, a long-acting granulocyte colony-stimulating factor, significantly reduced the duration of severe neutropenia in breast cancer patients undergoing chemotherapy compared to filgrastim, with mean durations of 1.06 days and 2.06 days respectively.

Both dosing regimens of mecapegfilgrastim (100 µg/kg and a fixed 6 mg dose) were well tolerated and showed comparable efficacy, making the fixed 6 mg dose a convenient option for patients due to its once-per-cycle administration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of mecapegfilgrastim for prophylaxis of chemotherapy-induced neutropenia in patients with breast cancer: a randomized, multicenter, active-controlled phase III trial. Xu, F., Zhang, Y., Miao, Z., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6200061/

Phase II study of ERC1671 plus bevacizumab versus ... The addition of ERC1671/GM-CSF/cyclophosphamide to bevacizumab resulted in a clinically meaningful survival benefit with minimal additional ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT01903330

NCT01903330 | ERC1671/GM-CSF/Cyclophosphamide for ... Overall Survival at 12 months of patients with recurrent, bevacizumab naïve glioblastoma treated with ERC1671 in combination with GM-CSF and cyclophosphamide ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05366062

NCT05366062 | ERC1671 to Treat Malignant Gliomas ... This is a treatment clinical trial to assess the efficacy of ERC1671 in combination with bevacizumab and pembrolizumab in patients with GBM that has ...

4. targetedonc.com targetedonc.com/view/fda-advises-on-termination-of-erc1671-clinical-trial-in-recurrent-glioblastoma

FDA Advises on Termination of ERC1671 Clinical Trial in ... A total of 10 patients were included in the first analysis and a 6-month overall survival rate of 100% was achieved as a well as a 12-month OS ...

5. withpower.com withpower.com/trial/phase-3-gliosarcoma-2-2014-d13c9

ERC1671 + GM-CSF + Cyclophosphamide for Glioblastoma Cyclophosphamide has shown acceptable safety in treating glioblastoma, with common side effects being blood-related issues like low white blood cell counts, ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5692303/

HOUT-17. A PRELIMINARY DATA REPORT ON A PHASE ... The proposed action of ERC1671 is the stimulation of the patients' immune system. This ongoing phase 2 study has a goal to determine the safety ...

7. onclive.com onclive.com/view/fda-recommends-termination-of-phase-2-trial-examining-immunotherapy-erc1671-in-glioblastoma

FDA Recommends Termination of Phase 2 Trial Examining ... Additionally, about 10% of patients who were given ERC1671 experienced total recovery and survived longer than 3 years after glioblastoma ...