33 Participants Needed

Trastuzumab + GM-CSF for Ependymoma

MW
DS
Overseen ByDeb Schissel, RN
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)

Trial Summary

What is the purpose of this trial?

This study plans to detect the presence of trastuzumab by mass spectroscopy in relapsed posterior fossa ependymoma (PFEPN) tumor specimen pre-treated with a single dose of intrathecal (IT) trastuzumab, as well as to evaluate toxicity of intrathecal trastuzumab in combination with subcutaneous (subQ) Granulocyte-macrophage colony-stimulating factor (GM-CSF) in children with relapsed PFEPN

Do I need to stop my current medications to join the trial?

Yes, you will need to stop certain medications. You cannot take systemic corticosteroids, investigational drugs, or other anti-cancer agents while participating in the trial.

Do I need to stop taking my current medications to join the trial?

Yes, you will need to stop taking certain medications. Specifically, you cannot be on systemic corticosteroids, other investigational drugs, or anti-cancer agents to participate in the trial.

What data supports the idea that Trastuzumab + GM-CSF for Ependymoma is an effective treatment?

The available research shows that Trastuzumab, when used for HER2-positive breast cancer with leptomeningeal metastases, has been effective in improving symptoms and slowing disease progression. For example, patients treated with intrathecal Trastuzumab experienced rapid symptom relief and remained stable for several months. Although this data is specific to breast cancer, it suggests that Trastuzumab can be effective in treating conditions involving the central nervous system. However, there is no direct data available for its use in Ependymoma, so its effectiveness for this condition remains uncertain.12345

What data supports the effectiveness of the drug Trastuzumab for treating leptomeningeal metastases in HER2-positive breast cancer?

Research shows that intrathecal (directly into the spinal fluid) administration of Trastuzumab can be effective for treating leptomeningeal metastases in HER2-positive breast cancer, with patients experiencing rapid symptom relief and disease control for several months.12345

What safety data exists for Trastuzumab + GM-CSF treatment?

The safety data for GM-CSF (Granulocyte-Macrophage Colony Stimulating Factor) includes potential side effects such as capillary leak syndrome, fever, skin rashes, and flu-like symptoms. In one case, a patient developed capillary leak syndrome during low-dose GM-CSF treatment, which was potentially fatal. GM-CSF has been used to treat chemotherapy-induced leukopenia and neutropenia, showing efficacy in increasing white cell counts but with noted side effects. Long-term safety, particularly regarding the risk of leukemia, has not been fully evaluated. There is no specific safety data for the combination of Trastuzumab and GM-CSF in ependymoma treatment in the provided research.678910

What safety data exists for Trastuzumab and GM-CSF treatments?

GM-CSF (also known as Sargramostim or Leukine) has been used in cancer treatments and can cause side effects like fever, skin rashes, and flu-like symptoms. In rare cases, it may lead to serious conditions like capillary leak syndrome, which involves fluid buildup in the body. Trastuzumab (also known as Herceptin) is generally considered safe but can have side effects like heart problems, so patients are usually monitored closely during treatment.678910

Is the drug GM-CSF, Trastuzumab a promising treatment for ependymoma?

Trastuzumab, when used in certain brain-related conditions like leptomeningeal carcinomatosis in breast cancer, has shown promise. It can be effective and safe, especially when administered directly into the spinal fluid, helping patients improve and manage their symptoms. This suggests that Trastuzumab could be a promising option for treating ependymoma, a type of brain tumor.1251112

How is the drug Trastuzumab + GM-CSF unique for treating ependymoma?

This treatment is unique because it combines trastuzumab, a drug that targets HER2-positive cancer cells, with GM-CSF, which stimulates the immune system, potentially offering a novel approach for ependymoma, a condition with limited standard treatment options. Trastuzumab has been used intrathecally (directly into the spinal fluid) in other cancers to overcome the blood-brain barrier, which may be relevant for treating brain-related conditions like ependymoma.1251112

Research Team

MM

Margaret Macy, MD

Principal Investigator

University of Colorado, Denver

Eligibility Criteria

This trial is for children and young adults aged between 1 and 21 years with a specific type of brain tumor called relapsed posterior fossa ependymoma. They must have good organ function, no widespread cancer in the spine or brain, and be able to undergo surgery if needed. Participants need acceptable performance scores indicating they can perform daily activities.

Inclusion Criteria

I am between 1 and 20 years old.
My PFEPN cancer has come back.
My heart is functioning well.
See 7 more

Exclusion Criteria

I have nodular metastatic spinal disease visible on MRI, making me ineligible for Stratum 1 but possibly eligible for Stratum 2.
I do not have any serious infections that are uncontrolled.
I do not have a specific type of ependymoma.
See 8 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single dose of intrathecal trastuzumab following a 5-day course of subcutaneous GM-CSF, with surgical resection planned 2-7 days after IT trastuzumab dosage.

2 weeks

Dose Finding

Participants receive IT trastuzumab in combination with GM-CSF to establish a maximum tolerated dosage.

1 month

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

  • GM-CSF
  • Trastuzumab
Trial OverviewThe study tests how well trastuzumab, given through the spinal canal after a dose of GM-CSF under the skin, works on this kind of brain tumor. It aims to see if trastuzumab reaches the tumor and assesses any side effects when combined with GM-CSF.
Participant Groups
2Treatment groups
Experimental Treatment
Group I: IT trastuzumab in combination with subQ GM-CSFExperimental Treatment1 Intervention
Patients with localized recurrent PFEPN will be treated with IT trastuzumab in combination with GM-CSF to establish a maximum tolerated dosage. GM-CSF will be administered at 250 mcg/m2/dose subQ daily for three (3) days prior to the IT trastuzumab dose.
Group II: IT trastuzumab after subQ GM-CSFExperimental Treatment1 Intervention
Patients with localized recurrent PFEPN will be treated with IT trastuzumab following 5-day course of subQ GM-CSF. Surgical resection should be planned (based on institutional surgical scheduling standards) for ideally 2-7 days after IT trastuzumab dosage.

GM-CSF is already approved in United States, European Union, Canada for the following indications:

🇺🇸
Approved in United States as Leukine for:
  • Neutropenia
  • Bone Marrow Transplantation
  • Leukemia
  • Lymphoma
  • HIV Infection
🇪🇺
Approved in European Union as Sargramostim for:
  • Neutropenia
  • Bone Marrow Transplantation
  • Leukemia
  • Lymphoma
🇨🇦
Approved in Canada as Leukine for:
  • Neutropenia
  • Bone Marrow Transplantation
  • Leukemia
  • Lymphoma

Find a Clinic Near You

Who Is Running the Clinical Trial?

University of Colorado, Denver

Lead Sponsor

Trials
1,842
Recruited
3,028,000+

Children's Hospital Colorado

Collaborator

Trials
121
Recruited
5,135,000+

Findings from Research

Intrathecal trastuzumab, when combined with systemic therapy, showed rapid symptomatic improvement and radiological response in two women with HER2 positive breast cancer and leptomeningeal carcinomatosis.
Both patients remained progression-free for at least seven months, suggesting that intrathecal trastuzumab may be a promising treatment option for this challenging condition.
Intrathecal trastuzumab for leptomeningeal carcinomatosis in patients with human epidermal growth factor receptor 2 positive breast cancer.Gulia, S., Gupta, S., Singh, A.[2020]
A 39-year-old woman with HER2-overexpressing metastatic breast cancer and leptomeningeal carcinomatosis showed significant improvement after receiving intrathecal trastuzumab, indicating its potential efficacy in this rare condition.
The use of an Ommaya reservoir for intrathecal administration allowed for effective delivery of trastuzumab, leading to low cell counts in cerebrospinal fluid for 11 months, suggesting a well-tolerated treatment approach for patients with compromised blood-brain barriers.
Application of intrathecal trastuzumab (Herceptintrade mark) for treatment of meningeal carcinomatosis in HER2-overexpressing metastatic breast cancer.Stemmler, HJ., Schmitt, M., Harbeck, N., et al.[2019]
In a study of 10 patients with leptomeningeal metastasis from HER2-positive breast cancer, the combination of neratinib and capecitabine showed a 60% overall survival rate at six months and a median overall survival of 10 months, indicating potential efficacy in a challenging patient population.
The treatment resulted in neurological benefits for 70% of patients, with a median duration of response of 6.5 months, suggesting that neratinib and capecitabine could be a safe and effective option for patients who have exhausted other treatment options.
Neratinib and Capecitabine for the Treatment of Leptomeningeal Metastases from HER2-Positive Breast Cancer: A Series in the Setting of a Compassionate Program.Pellerino, A., Soffietti, R., Bruno, F., et al.[2022]

References

Intrathecal trastuzumab for leptomeningeal carcinomatosis in patients with human epidermal growth factor receptor 2 positive breast cancer. [2020]
Application of intrathecal trastuzumab (Herceptintrade mark) for treatment of meningeal carcinomatosis in HER2-overexpressing metastatic breast cancer. [2019]
Neratinib and Capecitabine for the Treatment of Leptomeningeal Metastases from HER2-Positive Breast Cancer: A Series in the Setting of a Compassionate Program. [2022]
A phase I/II study of intrathecal trastuzumab in human epidermal growth factor receptor 2-positive (HER2-positive) cancer with leptomeningeal metastases: Safety, efficacy, and cerebrospinal fluid pharmacokinetics. [2023]
Sanctuary site leptomeningeal metastases in HER-2 positive breast cancer: A review in the era of trastuzumab. [2017]
Granulocyte-macrophage colony-stimulating factor increases the proportion of circulating dendritic cells after autologous but not after allogeneic hematopoietic stem cell transplantation. [2018]
Capillary leak syndrome during low dose granulocyte-macrophage colony-stimulating factor (rh GM-CSF) treatment of a patient in a continuous febrile state. [2019]
Granulocyte-macrophage colony-stimulating factor or granulocyte colony-stimulating factor infusion makes high-dose etoposide a safe outpatient regimen that is effective in lymphoma and myeloma patients. [2017]
[Clinical study of recombinant human granulocyte-macrophage colony-stimulating factor on chemotherapy-induced leukopenia]. [2013]
10.United Statespubmed.ncbi.nlm.nih.gov
Acute myeloid leukemia or myelodysplastic syndrome following use of granulocyte colony-stimulating factors during breast cancer adjuvant chemotherapy. [2020]
Intrathecal administration of trastuzumab with cytarabine and methotrexate in breast cancer patients with leptomeningeal carcinomatosis. [2015]
12.United Statespubmed.ncbi.nlm.nih.gov
A 4-week intrathecal toxicity and pharmacokinetic study with trastuzumab in cynomolgus monkeys. [2015]