Maintenance Chemotherapy vs Observation for Ependymoma

Not currently recruiting at 221 trial locations

Age: < 65

Sex: Any

Trial Phase: Phase 3

Sponsor: Children's Oncology Group

Disqualifiers: Metastatic disease, Spinal cord ependymoma, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: 25

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if adding maintenance chemotherapy after surgery and radiation can more effectively treat ependymoma, a type of brain tumor, compared to surgery and radiation alone. The trial includes different groups: one group receives chemotherapy and is monitored, while other groups receive chemotherapy and/or 3-Dimensional Conformal Radiation Therapy. The focus is on how well these treatments prevent tumor growth. This trial is for children and young adults aged 1-21 who have been newly diagnosed with intracranial ependymoma and have undergone surgery. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

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

The trial protocol does not specify whether you need to stop taking your current medications. However, it mentions that no prior treatment other than surgery and corticosteroids is allowed, which might imply that other medications should be stopped. 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 shows that the chemotherapy drugs used in this trial are well-studied. For example, Vincristine may cause side effects like constipation and nerve problems, but these are usually manageable. Doctors closely monitor any drop in blood cell counts that some patients might experience.

Carboplatin, often used with other drugs, effectively treats certain cancers. It may cause nausea or affect blood cells, but these effects are generally predictable and treatable.

Cisplatin is a strong drug with warnings. It can affect kidney function and cause nerve damage or nausea. However, doctors take steps to reduce these risks during treatment.

Cyclophosphamide is another important drug. It may cause side effects like hair loss and bladder issues, but healthcare teams monitor and manage these.

Etoposide is used for its ability to fight cancer. It may cause low blood cell counts or hair loss, but these effects are temporary.

Overall, these drugs have been used in many settings and are well understood. The trial's phase indicates they have been studied for safety in humans, and doctors will watch closely for any side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for ependymoma because they offer a more tailored approach compared to standard treatments like surgery and radiation alone. The trial explores the use of maintenance chemotherapy with drugs like vincristine, carboplatin, and etoposide, which could potentially improve outcomes by targeting cancer cells that remain after surgery. Additionally, the use of 3-Dimensional Conformal Radiation Therapy is noteworthy because it allows precise targeting of tumors, minimizing damage to surrounding healthy tissue. These aspects combine to potentially enhance treatment effectiveness and reduce side effects, making the approach promising for patients with varying resection outcomes.

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

Research has shown that chemotherapy drugs such as carboplatin, cisplatin, cyclophosphamide, etoposide, and vincristine can effectively treat brain tumors, including ependymoma. In this trial, participants will receive various combinations of these drugs in different arms. For instance, carboplatin has been found to shrink tumors in 43% of children with recurring brain tumors. Cisplatin is commonly used for various cancers and works well when applied directly to tumors. Cyclophosphamide and etoposide have demonstrated a 69% response rate in patients with difficult-to-treat brain tumors. Vincristine is known to extend survival, with rates ranging from 50% to 75% over ten years, depending on factors such as tumor removal extent and patient age. Combining these drugs with radiation therapy, which targets and destroys tumor cells, may enhance these outcomes. Participants in this trial may receive chemotherapy alone, chemotherapy with radiation, or observation, depending on their assigned treatment arm. ^{1 2 6 7 8}

Who Is on the Research Team?

Amy A Smith

Principal Investigator

Children's Oncology Group

Are You a Good Fit for This Trial?

This trial is for children and young adults aged 1-21 with newly diagnosed brain ependymoma, who've had surgery but no other treatment. It's not for those with spinal cord ependymoma or certain other types, pregnant or breastfeeding individuals, or patients with metastatic disease.

Inclusion Criteria

My child has ependymoma but can still participate in the study despite any neurological issues.

I have been newly diagnosed with a specific type of brain tumor called ependymoma.

REGULATORY: All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met

Exclusion Criteria

I have only had surgery or used corticosteroids for my condition.

I do not have cancer spread beyond the primary site as confirmed by MRIs and CSF tests.

Pregnant female patients are not eligible for this study

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction Chemotherapy

Patients receive induction chemotherapy with vincristine, carboplatin, cyclophosphamide, and etoposide to achieve complete response or prepare for further treatment

7 weeks

Multiple visits for chemotherapy administration

Radiation Therapy

Patients undergo conformal radiotherapy over 6-7 weeks

6-7 weeks

Daily visits for radiation therapy

Maintenance Chemotherapy

Patients receive maintenance chemotherapy with vincristine, etoposide, cisplatin, and cyclophosphamide

12 weeks

Every 21 days for 4 courses

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

Every 4 months for 5 years, then annually

What Are the Treatments Tested in This Trial?

Interventions

• 3-Dimensional Conformal Radiation Therapy
• Carboplatin
• Cisplatin
• Clinical Observation
• Cyclophosphamide
• Etoposide
• Laboratory Biomarker Analysis
• Vincristine

Trial Overview The study tests if maintenance chemotherapy after surgery and radiation helps more than just surgery and radiation alone in treating brain ependymoma. Some will receive combination chemotherapy drugs plus specialized radiation therapy aimed at killing tumor cells while sparing healthy tissue.

How Is the Trial Designed?

Group I: Arm II (radiotherapy, chemotherapy) Experimental Treatment 8 Interventions

Patients with supratentorial ependymoma (Grade II without GTR1 or Grade III) or any infratentorial ependymoma who have undergone gross or near total resection (GTR or NTR) or achieved CR either after first or second resection or after post-operative induction chemotherapy are randomized to undergo conformal radiotherapy over 6-7 weeks followed by maintenance chemotherapy. Maintenance chemotherapy comprised of vincristine IV on days 1, 8, and 15 of cycles 1-3 only, etoposide IV over 60-120 minutes on days 1-3, cisplatin IV over 1-8 hours on day 1, and cyclophosphamide IV over 30-60 minutes on days 2-3. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. Patients without GTR or NTR at enrollment require induction chemotherapy (see Arm I) and possibly second surgery before randomization.

Group II: Arm I (chemotherapy, observation) Experimental Treatment 7 Interventions

Patients with classic histology(WHO Grade II) supratentorial ependymoma who have undergone microscopic gross total resection (GTR1) or achieved CR either after first or second resection or after post-operative induction chemotherapy are assigned to observation. For patients without GTR1, induction chemotherapy is comprised of vincristine intravenously (IV) over 1 minute on days 1 and 8 of cycles 1 and 2, carboplatin IV over 15-60 minutes on day 1 of cycles 1 and 2, and cyclophosphamide IV over 30-60 minutes on days 1-2 of cycle 1 only. Patients also receive etoposide IV over 60-120 minutes on days 1-3 of cycle 2 only. Cycle 1 continues for 3 weeks and cycle 2 continues for 4 weeks in the absence of disease progression or unacceptable toxicity.

Group III: ARM IV (radiotherapy, chemotherapy) Active Control 8 Interventions

Patients with subtotal resection after induction chemotherapy (see Arm I) and second surgery are nonrandomly assigned to Arm II treatment.

Group IV: Arm III (radiotherapy, observation) Active Control 3 Interventions

Patients with supratentorial ependymoma (Grade II without GTR1 or ST Grade III) or any infratentorial ependymoma (Grade II or III) who have undergone gross or near total resection or achieved CR either after first or second resection or after post-operative induction chemotherapy are randomized to undergo conformal radiotherapy over 6-7 weeks and then undergo observation. Patients without GTR or NTR at enrollment require induction chemotherapy (see Arm I) and possibly second surgery before randomization.

3-Dimensional Conformal Radiation Therapy is already approved in United States, European Union, Canada, Japan, China, Switzerland for the following indications:

Approved in United States as 3D-CRT for:

• Various types of cancer, including gynecologic cancers

Approved in European Union as 3D-CRT for:

• Various types of cancer, including gynecologic cancers

Approved in Canada as 3D-CRT for:

• Various types of cancer, including gynecologic cancers

Approved in Japan as 3D-CRT for:

• Various types of cancer, including gynecologic cancers

Approved in China as 3D-CRT for:

• Various types of cancer, including gynecologic cancers

Approved in Switzerland as 3D-CRT for:

• Various types of cancer, including gynecologic cancers

Who Is Running the Clinical Trial?

Children's Oncology Group

Lead Sponsor

Trials

467

Recruited

241,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Complete surgical resection of ependymomas significantly improves patient survival, making it crucial to evaluate the extent of disease through cerebrospinal fluid cytology and MRI before deciding on treatment.

For patients with residual disease who cannot undergo further surgery, limited-field radiotherapy is typically used, but the effectiveness of craniospinal irradiation remains debated due to the tendency for local recurrences.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ependymomas. Chowdhary, S., Green, MR., Chamberlain, M.[2022]

Childhood intracranial ependymoma has a poor prognosis, particularly in young children and those who cannot undergo complete surgical resection, with about two-thirds experiencing recurrence even without visible tumor remnants.

Cisplatin is the only chemotherapy agent that has shown some effectiveness in treating ependymoma, but overall, these tumors are generally resistant to chemotherapy, highlighting the need for new treatment strategies and well-designed clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Childhood ependymoma: a systematic review of treatment options and strategies. Grill, J., Pascal, C., Chantal, K.[2022]

In a multicenter study of lung cancer patients undergoing carboplatin-based chemotherapy, a one-day dexamethasone (DEX) regimen combined with 5-HT3RA and aprepitant (APR) resulted in significantly higher rates of delayed nausea compared to a multiple-day DEX regimen.

The findings suggest that while a DEX-sparing strategy may be considered, it should be approached with caution due to the increased risk of nausea, indicating the need for careful patient selection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of one-day versus multiple-day dexamethasone for chemotherapy-induced nausea and vomiting in lung cancer patients receiving carboplatin-based chemotherapy: a propensity score-matched analysis. Hayashi, T., Shimokawa, M., Mizuki, F., et al.[2021]

In adults with intra-cranial ependymal tumors, there is a lack of universally accepted prognostic factors and treatment guidelines due to the rarity of these tumors and limited data.

Current evidence from a phase III trial in children shows that adding chemotherapy (lomustine, vincristine, and prednisone) to cranio-spinal irradiation does not improve survival compared to radiation therapy alone, suggesting that chemotherapy should only be used in controlled clinical trials for adults.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Guidelines for the treatment of adult intra-cranial grade II-III ependymal tumours. Reni, M.[2004]

In a study of 69 patients undergoing cisplatin chemotherapy for testicular cancer, aprepitant significantly improved the complete response rate to 42% compared to only 13% with placebo, indicating its efficacy in preventing nausea and vomiting.

Patients overwhelmingly preferred the aprepitant treatment cycle, with no reported toxicity, suggesting that aprepitant is a safe and effective addition to standard antiemetic therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized, double-blind, placebo-controlled, phase III cross-over study evaluating the oral neurokinin-1 antagonist aprepitant in combination with a 5HT3 receptor antagonist and dexamethasone in patients with germ cell tumors receiving 5-day cisplatin combination chemotherapy regimens: a hoosier oncology group study. Albany, C., Brames, MJ., Fausel, C., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10489494/

JS01.5.A PHASE 2 TRIAL OF CARBOPLATIN AND ... CONCLUSION. This treatment regimen was safe and met the primary efficacy endpoint of 12-month PFS rate. The improvement in disease-related symptoms in brain ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT01295944

Carboplatin and Bevacizumab for Recurrent Ependymoma The choice of carboplatin is justified by the fact that, as detailed above, this remains the most effective agent in this disease, and extensive toxicity data ...

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0936655510003778

Carboplatin Chemotherapy in Patients with Recurrent High ... The median survival was 19.4 weeks (27.9 weeks for patients with grade III glioma and 8.1 weeks for patients with grade IV glioma). Among patients with either ...

4. withpower.com withpower.com/trial/carboplatin-regimens-for-brain-tumors-9dbf7

Carboplatin Regimens for Brain Tumors · Info for Participants In a study involving 44 patients with recurrent childhood brain tumors, carboplatin was found to have a disease-specific response rate of 43% in ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4307774/

CARBOPLATIN-BASED PRIMARY CHEMOTHERAPY FOR ... For medulloblastoma, the five-year PFS is 26% ± 9%; for EP 33 ± 10%; for CPCA, 80 ± 18%; for PNET and atypical teratoid rhabdoid tumor (ATRT) 0%. Localized ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT01295944?term=AREA%5BBasicSearch%5D(AREA%5BBasicSearch%5D(AREA%5BBasicSearch%5D(AREA%5BConditionSearch%5D(%22Anaplastic%20Ependymoma%22))))&rank=2

Carboplatin and Bevacizumab for Recurrent Ependymoma Also called a data safety and monitoring board, or DSMB. Early Phase 1 (formerly listed as Phase 0). A phase of research used to describe exploratory trials ...

7. go.drugbank.com go.drugbank.com/drugs/DB00958

Carboplatin: Uses, Interactions, Mechanism of Action Carboplatin is indicated in combination with an established combination of chemotherapeutic agents for the initial treatment of advanced ovarian carcinoma.

8. cancer.gov cancer.gov/clinicaltrials/NCT01295944

Carboplatin and Bevacizumab for Recurrent Ependymoma Description. The goal of this clinical research study is to learn if the combination of bevacizumab and carboplatin can help to control recurrent ependymoma.