Chemotherapy for Choroid Plexus Cancer

Overseen by Mark Souweidane, M.D.

Age: Any Age

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Waitlist Available

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

Trial Summary

What is the purpose of this trial?

This trial will test if delivering cancer drugs directly to brain tumors through blood vessels is safe and effective for patients with specific types of brain tumors. The goal is to shrink the tumors.

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 evidence supports the effectiveness of the drugs Carboplatin, Melphalan, and Topotecan for treating 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. Additionally, a study found that a combination of melphalan with another drug increased survival in a mouse model of choroid plexus carcinoma, suggesting potential effectiveness. However, the overall survival rates remain unsatisfactory, indicating a need for further research. ^{1 2 3 4 5}

Is chemotherapy for choroid plexus cancer generally safe in humans?

Chemotherapy drugs like carboplatin and topotecan have been studied in various cancers, including brain and spinal cord tumors. While they show promise in treating these conditions, they can cause side effects like myelosuppression (a decrease in bone marrow activity leading to fewer blood cells) and neutropenia (low levels of a type of white blood cell), which are important safety considerations. ^{1 2 6 7 8}

How does the chemotherapy drug combination of Carboplatin, Melphalan, and Topotecan differ from other treatments for choroid plexus cancer?

The chemotherapy combination of Carboplatin, Melphalan, and Topotecan is unique because it includes Melphalan and Topotecan, which are not commonly highlighted in existing studies for choroid plexus cancer, where drugs like etoposide and cyclophosphamide are more frequently mentioned. This combination may offer a novel approach, especially since no optimal treatment has been established for this rare cancer. ^{1 2 4 5 9}

Research Team

Mark Souweidane, M.D.

Principal Investigator

Weill Medical College of Cornell University

Eligibility Criteria

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

Trial Timeline

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

Treatment Details

Interventions

• Carboplatin (Platinum-based compound)
• Melphalan (Alkylating agents)
• Topotecan (Topoisomerase I inhibitors)

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.

Participant Groups

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 Canada for the following indications:

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+

Dr. Robert Min

Weill Medical College of Cornell University

Chief Executive Officer since 2024

MD, MBA

Dr. Adam R. Stracher

Weill Medical College of Cornell University

Chief Medical Officer since 2024

MD

Findings from Research

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]

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]

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]

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]

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]

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Which therapy works better in choroid plexus carcinomas? [2021]

2. United States pubmed.ncbi.nlm.nih.gov

Use of ifosfamide, carboplatin, and etoposide chemotherapy in choroid plexus carcinoma. [2013]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Preclinical validation of a novel therapeutic strategy for choroid plexus carcinoma. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Response of a recurrent choroid plexus tumor to combination chemotherapy. [2019]

5. Germany pubmed.ncbi.nlm.nih.gov

Chemotherapy of choroid plexus carcinoma. [2005]

6. United States 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. [2013]

7. Germany 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. [2021]

8. United States pubmed.ncbi.nlm.nih.gov

Topotecan in combination chemotherapy. [2017]

9. Japan pubmed.ncbi.nlm.nih.gov

[A study of usefulness of chemotherapy in long-term survival choroid plexus carcinoma case of childhood]. [2013]