Chemotherapy for Choroid Plexus Cancer

Overseen By Colleen Sanders

Age: Any Age

Sex: Any

Trial Phase: Phase 1

Sponsor: Weill Medical College of Cornell University

Must not be taking: Anticancer agents, Enzyme anticonvulsants

Disqualifiers: Pregnancy, Uncontrolled seizures, Heart failure, others

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

Compensation: Varies

Number of Visits: 2

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety and effectiveness of intra-arterial chemotherapy for individuals with atypical choroid plexus papilloma (ACPP) or choroid plexus carcinoma (CPC). The treatment delivers three chemotherapy drugs—Carboplatin, Melphalan, and Topotecan—directly into the arteries to shrink the tumor before a second surgery. Researchers aim to determine if this approach can enhance surgical success. Individuals with a confirmed diagnosis of ACPP or CPC, whether newly diagnosed, with residual cancer post-surgery, or experiencing a recurrence, might be suitable candidates if their condition is stable and they meet other health criteria. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to be among the first to receive this innovative approach.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you must not be on any other anticancer or investigational agents. If you are taking dexamethasone, your dose must be stable or decreasing for at least one week before joining the trial.

What prior data suggests that intra-arterial chemotherapy is safe for treating choroid plexus cancer?

Research has shown that using a combination of the drugs Carboplatin, Melphalan, and Topotecan in a type of chemotherapy targeting the arteries is expected to have manageable side effects for patients with brain tumors. These drugs have been used in other treatments, providing some knowledge about their safety. For example, Carboplatin can cause side effects like nausea and low blood counts, but these are usually manageable. Melphalan and Topotecan can also cause side effects such as tiredness and hair loss.

Since this study is in the early stages, its main goal is to confirm that the treatment is safe for humans. Researchers are closely monitoring for any new or unexpected side effects. Overall, the treatment appears promising and safe, but more testing is needed to be certain. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard chemotherapy treatments for choroid plexus cancer, which are typically delivered intravenously, this new approach uses intra-arterial infusion to deliver carboplatin, melphalan, and topotecan directly to the brain. This delivery method is exciting because it allows for higher concentrations of the drugs to reach the tumor while minimizing exposure to the rest of the body, potentially reducing side effects. Researchers are particularly interested in this approach because it could enhance the effectiveness of chemotherapy by targeting the cancer more precisely, offering a promising new direction for treating this rare condition.

What evidence suggests that intra-arterial chemotherapy could be effective for choroid plexus cancer?

Research has shown that administering a special type of chemotherapy directly into the arteries might help treat choroid plexus carcinoma, a rare brain cancer. In this trial, participants will receive a combination of three drugs—carboplatin, melphalan, and topotecan—via intra-arterial infusion. Studies have found that carboplatin can significantly improve survival rates for patients with this cancer. Delivering chemotherapy directly to the tumor may help shrink it and increase the success of surgery. Early evidence suggests this method could safely and effectively reduce tumor size before surgery. ^{1 2 3 6 7}

Who Is on the Research Team?

Mark Souweidane, M.D.

Principal Investigator

Weill Medical College of Cornell University

Are You a Good Fit for This Trial?

This trial is for individuals with a specific type of brain tumor, either newly diagnosed, remaining after treatment, or returned. They must be relatively active (able to care for themselves), have normal body functions as tested recently, and not be on increasing doses of steroids. Pregnant women and those with serious unrelated illnesses or taking certain other drugs are excluded.

Inclusion Criteria

I can care for myself but may need occasional help.

My diagnosis is ACPP or CPC, whether it's new, remaining, or has come back.

My organ and bone marrow functions are normal.

Exclusion Criteria

I am not pregnant or breastfeeding.

I am not currently taking any cancer treatment or experimental drugs.

Subjects with any clinically significant unrelated systemic illness likely to interfere with the study procedures or results

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Cerebral Angiogram

Subjects undergo a cerebral angiogram to determine the ideal arteries for drug infusion

1 week

1 visit (in-person)

Intra-arterial Chemotherapy

Subjects receive intra-arterial chemotherapy with Melphalan, Carboplatin, and Topotecan

1 week

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

7 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Carboplatin
• Melphalan
• Topotecan

Trial Overview The study tests intra-arterial chemotherapy using Melphalan, Carboplatin, and Topotecan in patients before they undergo a second surgery. The goal is to see if this approach safely shrinks the tumors and improves surgical outcomes.

How Is the Trial Designed?

Group I: Intra-arterial Chemotherapy Experimental Treatment 3 Interventions

Subjects are pre-treated with heparin, and then given single doses of Melphalan, Carboplatin, and Topotecan consecutively via intra-arterial infusion. Multiple arteries may be used, with the total dose of the drugs remaining the same.

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

Approved in United States as Paraplatin for:

• Ovarian cancer
• Testicular cancer
• Lung cancer
• Head and neck cancer
• Brain cancer

Approved in European Union as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer

Approved in Canada as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer
• Testicular cancer

Who Is Running the Clinical Trial?

Weill Medical College of Cornell University

Lead Sponsor

Trials

1,103

Recruited

1,157,000+

Published Research Related to This Trial

Choroid plexus carcinoma is a rare and aggressive tumor, and achieving a complete surgical resection is crucial for potential cure.

Adjuvant therapies like chemotherapy may help shrink the tumor and improve the chances of complete resection, especially when initial surgery is not feasible due to the tumor's fragile and highly vascular nature.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chemotherapy of choroid plexus carcinoma. Greenberg, ML.[2005]

In a study of 14 pediatric patients with choroid plexus carcinomas, neoadjuvant ICE chemotherapy followed by second-look surgery resulted in a high rate of complete or near-complete tumor resection, with 11 out of 12 patients achieving over 95% resection.

Despite the successful surgical outcomes and avoidance of radiation therapy, most survivors (6 out of 8) experienced significant neurocognitive and/or sensory deficits, highlighting the need for careful consideration of long-term effects in treatment planning.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of ifosfamide, carboplatin, and etoposide chemotherapy in choroid plexus carcinoma. Lafay-Cousin, L., Mabbott, DJ., Halliday, W., et al.[2013]

This study conducted the first high-throughput screening on a patient-derived choroid plexus carcinoma (CPC) cell line, identifying 427 potential therapeutic targets and several synergistic drug combinations that could lead to new treatment strategies for this aggressive brain tumor.

The combination of melphalan and elimusertib, delivered via intra-arterial administration, significantly improved survival in a CPC mouse model, highlighting the effectiveness of this approach and the importance of targeting key oncogenic pathways.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preclinical validation of a novel therapeutic strategy for choroid plexus carcinoma. Martin, B., Garman, T., Laramee, M., et al.[2023]

A meta-analysis of 906 patients with choroid plexus carcinomas (CPCs) identified etoposide as the most effective chemotherapy drug, showing a high response rate in 17 out of 36 patients treated.

Survival analysis indicated that cyclophosphamide, etoposide, and carboplatin significantly improved outcomes for CPC patients, with etoposide being the most promising candidate for inclusion in future treatment protocols, although overall survival rates remain low.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Which therapy works better in choroid plexus carcinomas? Berrak, SG., Liu, DD., Wrede, B., et al.[2021]

A treatment regimen combining thiotepa, topotecan, and carboplatin was administered to ten pediatric patients with recurrent central nervous system tumors, showing potential to consolidate remission in this challenging group.

Out of the ten patients, four are long-term survivors, particularly those with no evidence of disease at the time of stem cell rescue, suggesting that the extent of disease prior to treatment significantly influences outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Thiotepa/topotecan/carboplatin with autologous stem cell rescue in recurrent/refractory/poor prognosis pediatric malignancies of the central nervous system. Gilheeney, SW., Khakoo, Y., Souweidane, M., et al.[2013]

A 7-year-old girl diagnosed with choroid plexus carcinoma has survived for 11 years after undergoing two tumor surgeries and receiving chemotherapy and radiotherapy, highlighting a rare long-term survival case.

The case suggests that chemotherapy, particularly with drugs like cisplatin, carboplatin, and etoposide, may be beneficial in treating choroid plexus carcinoma in children, despite the generally poor prognosis associated with this cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[A study of usefulness of chemotherapy in long-term survival choroid plexus carcinoma case of childhood]. Takahashi, H., Kusanagi, H., Yamaguchi, F., et al.[2013]

This report presents the first documented case of a choroid plexus papilloma (CPP) responding positively to a combination chemotherapy regimen of cisplatin, bleomycin, and vinblastine, suggesting a potential new treatment avenue.

The findings indicate that this chemotherapy combination could be a viable option for future clinical trials in patients with recurrent choroid plexus tumors after surgery and/or radiotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Response of a recurrent choroid plexus tumor to combination chemotherapy. Maria, BL., Graham, ML., Strauss, LC., et al.[2019]

The combination treatment of tamoxifen, topotecan, and carboplatin was found to have a recommended phase II dosing regimen, with tamoxifen at 100 mg twice daily and topotecan at 0.75 mg/m² per day, showing potential efficacy in patients with high-grade gliomas and other cancers.

Topotecan demonstrated significant penetration into the cerebrospinal fluid (CSF), with a median CSF/plasma ratio of 19.4%, indicating its potential effectiveness in treating central nervous system tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Plasma and cerebrospinal fluid pharmacokinetics of topotecan in a phase I trial of topotecan, tamoxifen, and carboplatin, in the treatment of recurrent or refractory brain or spinal cord tumors. Morgan, RJ., Synold, T., Mamelak, A., et al.[2021]

Topotecan, a drug that targets topoisomerase I, has shown significant antitumor activity when combined with various chemotherapy agents like cisplatin and doxorubicin in both adult and pediatric patients with solid tumors.

The main side effect of these combination therapies is myelosuppression, particularly neutropenia, which limits the dosage; however, many early studies have reported major responses, indicating the potential effectiveness of these regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Topotecan in combination chemotherapy. Rowinsky, EK., Kaufmann, SH.[2017]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04994977?term=NCT04994977&rank=1

Intra-Arterial Chemotherapy for Newly Diagnosed ... This study will test the safety and efficacy of intra-arterial chemotherapy in subjects with newly diagnosed, residual, or recurrent atypical choroid plexus ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10174050/

Preclinical Validation of a Novel Therapeutic Strategy for ... CPC is a rare brain tumor that commonly presents in infancy with a reported five-year survival of only 40% to 50% (e.g.) and accounting for 1–4% of all brain ...

3. withpower.com withpower.com/trial/phase-1-choroid-plexus-neoplasms-7-2021-843a1

Chemotherapy for Choroid Plexus Cancer Carboplatin has shown a statistically significant treatment benefit in improving survival for choroid plexus carcinoma patients, as indicated by a meta-analysis ...

4. nyp.org nyp.org/advances/article/how-an-interventional-chemotherapeutic-approach-is-advancing-the-treatment-of-rare-pediatric-brain-cancers

How an Interventional Chemotherapeutic Approach Is ... Intra-Arterial Chemotherapy (IAC) Shows Potential for Choroid Plexus Carcinoma. Dr. Gobin's research with retinoblastoma became a building block ...

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/22863945/

Three-drug Intra-Arterial Chemotherapy Using ... Aims: To report outcomes with selective intra-arterial chemotherapy (SIAC) using simultaneous carboplatin, topotecan, and melphalan for advanced ...

6. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0168365923002663

Preclinical validation of a novel therapeutic strategy for ... CPC is a rare brain tumor that commonly presents in infancy with a reported five-year survival rate of only 40% to 50% (e.g. [[1], [2], [3]]) and accounting for ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12293580/

Old Tools in a New Era - PubMed Central - NIH In very young children with embryonal CNS tumors, intensive high-dose chemotherapy approaches have been used with varied increased survival in medulloblastoma, ...