Carboplatin + Radiotherapy for Relapsing Glioblastoma

Overseen By David Fortin, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Université de Sherbrooke

Disqualifiers: Severe psychiatric, Auto-immune, Pregnancy, others

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

Compensation: Varies

Number of Visits: 11

Duration: 2 weeks for initial radiation, followed by monthly IA carboplatin for up to 12 months

35 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment approach for people with glioblastoma, an aggressive brain cancer that often returns after treatment. The study combines carboplatin, a chemotherapy drug, with radiation therapy to determine if this mix can better control the cancer. It targets those who have already undergone surgery, radiation, and chemotherapy (known as the Stupp protocol) but whose cancer has returned. Participants must have glioblastoma confirmed by a doctor, visible on an MRI, and have already tried standard treatments. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new approach.

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

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

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

Studies have shown that using carboplatin with radiotherapy to treat glioblastoma can cause mild side effects, such as nausea and reduced blood platelets, which help blood clot. Earlier research indicated that this treatment allowed patients to live without disease progression for about six months and overall survival for about 14 months.

While patients might experience some side effects, they are usually not severe. Additionally, because carboplatin is used in other treatments, doctors understand its effects in the body, aiding in predicting and managing side effects. The treatment undergoes careful monitoring to ensure it meets the highest safety standards. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of carboplatin and radiotherapy for relapsing glioblastoma because it offers a novel approach compared to standard treatments like temozolomide and bevacizumab. This trial explores varying doses of radiation (15 Gy to 35 Gy) paired with carboplatin, aiming to optimize the balance between efficacy and safety. Unlike conventional treatments that often rely on systemic chemotherapy, this approach uses intra-arterial delivery, potentially enhancing drug concentration at the tumor site and improving outcomes. By testing different radiation levels, the trial seeks to uncover the most effective combination, which could lead to better management of this aggressive brain cancer.

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

Research shows that intraarterial (IA) carboplatin for treating relapsing glioblastoma has a 70% success rate. This method has increased overall survival to 22 months and extended the time before disease progression to 5 months. In this trial, participants will receive varying doses of carboplatin combined with different levels of radiotherapy. This combination has been shown to enhance treatment effectiveness by making cancer cells more sensitive to radiation. Previous studies have shown encouraging results, with 58% of patients living for one year and 31% living for two years when treated with similar combined therapies. This approach helps the treatment reach the brain more effectively by targeting the blood-brain barrier, which typically prevents drugs from entering the brain. ^{1 2 3 4 5}

Who Is on the Research Team?

David Fortin, MD

Principal Investigator

CRC-CHUS

Are You a Good Fit for This Trial?

This trial is for adults over 18 with glioblastoma multiforme that has relapsed after initial treatment with radiotherapy and temozolomide. Participants must have a Karnofsky performance status of 60-100% and adequate blood counts, without impaired bone marrow function or significantly elevated bilirubin levels.

Inclusion Criteria

Hemoglobin > 8 g/dL

Bilirubin ≤ 2 times normal value

My glioblastoma has worsened on MRI after treatment with radiotherapy and Temozolomide.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Surgery

Surgery for cytoreduction and tumor sample collection

1 week

1 visit (in-person)

Treatment

Combination of re-irradiation and intraarterial carboplatin chemotherapy

2 weeks for initial radiation, followed by monthly IA carboplatin for up to 12 months

10 visits (in-person) for radiation, monthly visits for IA carboplatin

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Monthly MRI and assessments

What Are the Treatments Tested in This Trial?

Interventions

• Carboplatin
• Radiation

Trial Overview The study tests intraarterial (IA) carboplatin combined with re-irradiation in patients whose glioblastoma has recurred. The goal is to find the optimal radiation dose alongside IA chemotherapy, assessing tumor response, quality of life, neurocognition, and drug delivery within the brain.

How Is the Trial Designed?

Group I: Arm 6: IA Carbo + radiation Experimental Treatment 1 Intervention

400 mg/m\^2 carbo + 35 Gy

Group II: Arm 5: IA Carbo + radiation Experimental Treatment 1 Intervention

400 mg/m\^2 carbo + 30 Gy

Group III: Arm 4: IA Carbo + radiation Experimental Treatment 1 Intervention

400 mg/m\^2 carbo + 25 Gy

Group IV: Arm 3: IA Carbo + radiation Experimental Treatment 1 Intervention

400 mg/m\^2 carbo + 20 Gy

Group V: Arm 2: IA Carbo + radiation Experimental Treatment 1 Intervention

400 mg/m\^2 carbo + 18 Gy

Group VI: Arm 1: IA Carbo + radiation Experimental Treatment 1 Intervention

400 mg/m\^2 carbo + 15 Gy

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?

Université de Sherbrooke

Lead Sponsor

Trials

317

Recruited

79,300+

Published Research Related to This Trial

In a study of 56 patients with newly diagnosed glioblastoma, treatment with radiotherapy and concurrent carboplatin plus teniposide followed by carmustine resulted in a median survival time of 12.5 months and a time to progression of 7.5 months.

The treatment was generally well-tolerated, with acceptable levels of toxicity, although 7.1% of patients experienced radiation necrosis, indicating that while the regimen is effective, careful monitoring for side effects is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carboplatin and teniposide concurrent with radiotherapy in patients with glioblastoma multiforme: a phase II study. Brandes, AA., Rigon, A., Zampieri, P., et al.[2020]

In a study involving 44 patients with recurrent childhood brain tumors, carboplatin was found to have a disease-specific response rate of 43% in medulloblastoma, indicating its potential effectiveness in treating this type of cancer.

Carboplatin demonstrated a favorable safety profile with mild side effects, such as low emetic effects and no significant auditory or renal toxicity, making it a promising candidate for further studies in combination therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carboplatin and recurrent childhood brain tumors. Allen, JC., Walker, R., Luks, E., et al.[2017]

In a clinical trial involving 14 patients with newly diagnosed glioblastoma multiforme (GBM) and anaplastic astrocytoma (AA), low-dose carboplatin was safely administered alongside radiotherapy without significant toxicities, suggesting a tolerable treatment approach.

Despite the safety of the combined therapy, the results showed no improvement in survival time compared to historical data for patients treated with radiotherapy alone, indicating that carboplatin may not enhance the effectiveness of radiation in these types of brain tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daily low-dose carboplatin as a radiation sensitizer for newly diagnosed malignant glioma. Peterson, K., Harsh, G., Fisher, PG., et al.[2020]

In a study of 15 patients with relapsed high-grade glioma, carboplatin and iproplatin demonstrated some effectiveness, with one patient from each treatment achieving partial remission based on CT scans.

However, the study was halted due to significant toxicity, including severe myelosuppression and fatal neurotoxicity in one patient, highlighting safety concerns with these treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Activity and toxicity of carboplatin and iproplatin in relapsed high-grade glioma. Twelves, CJ., Ash, CM., Miles, DW., et al.[2019]

In a study of 20 patients with high-grade glioma, those treated with high doses of carboplatin had a mean survival time of 10.45 months, which was better than the control group treated with BCNU, who had a mean survival time of 9.85 months.

The high-dose carboplatin treatment was generally well tolerated, and 10% of patients survived beyond 18 months, compared to 0% in the control group, suggesting that carboplatin may be a more effective option for this type of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravenous administration of high doses of carboplatin in multimodal treatment of high grade gliomas: a phase II study. Lunardi, P., Osman Farah, J., Mastronardi, L., et al.[2019]

Fractionated stereotactic re-irradiation shows a 12-month overall survival rate of 33.1% and a progression-free survival rate of 13.4% in patients with recurrent glioblastoma, based on a meta-analysis of eight studies involving 307 patients.

The treatment has a low incidence of radiation necrosis, indicating it is a relatively safe option for patients, with factors like age and radiation dose affecting survival outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fractionated stereotactic re-irradiation for recurrent glioblastoma: A systematic review and meta-analysis. Luo, T., Feng, J., Sun, P.[2023]

Combining radiation therapy with intracerebral administration of carboplatin significantly improved survival in F98 glioma-bearing rats, achieving a mean survival time of 107.7 days and a 43% cure rate, compared to 30-35 days for radiation alone.

The study found that using a pump for carboplatin delivery combined with radiation therapy was more effective than convection enhanced delivery (CED), but both methods showed promise, with CED yielding survival rates comparable to those achieved with higher radiation doses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiation therapy combined with intracerebral administration of carboplatin for the treatment of brain tumors. Yang, W., Barth, RF., Huo, T., et al.[2021]

In a study of 25 patients with glioblastoma multiforme, neoadjuvant carboplatin chemotherapy showed promising results, with 6 partial responses and 1 complete response among those with assessable tumors, indicating its potential efficacy before radiation therapy.

The treatment was found to be feasible with modest side effects, and the median survival of 19.2 months suggests that carboplatin could be a valuable option in the management of newly diagnosed glioblastoma multiforme, warranting further research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carboplatin chemotherapy before irradiation in newly diagnosed glioblastoma multiforme. Gruber, ML., Glass, J., Choudhri, H., et al.[2019]

The addition of temozolomide to radiotherapy has shown a statistically significant survival benefit for patients with glioblastoma, marking a notable success in treatment.

Despite previous treatment strategies failing to improve outcomes, this combination therapy has minimal acute toxicity, highlighting its potential as a safer option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Radiotherapy for glioblastomas: from radiobiology to concomitant chemotherapy]. Simon, JM., Toubiana, T., Lang, P., et al.[2018]

In a study of 32 patients with recurrent glioma who had previously undergone radiation and chemotherapy, 50% showed a response or stabilization of their disease after two infusions of carboplatin, indicating its efficacy in this challenging patient population.

The median time to tumor progression was 19 weeks and the median survival duration was 38 weeks, with thrombocytopenia being the main side effect, affecting one-third of patients, but no significant neurological or renal toxicities were observed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II study of intravenous carboplatin for the treatment of recurrent gliomas. Warnick, RE., Prados, MD., Mack, EE., et al.[2022]

Citations

1. withpower.com withpower.com/trial/phase-2-glioblastoma-6-2018-5f0af

Carboplatin + Radiotherapy for Relapsing Glioblastoma Progression-free survival (PFS) with this treatment is only 6.9 months and relapse is the norm. The rationale behind the fact that limited chemotherapy agents ...

2. 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 ...

3. nature.com nature.com/articles/s41467-024-45818-7

Repeated blood–brain barrier opening with a nine-emitter ... The low activity of carboplatin against GBM can be explained by the heterogeneity of cancer cell susceptibility to the drug and by the fact that ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT03672721

IA Carboplatin + Radiotherapy in Relapsing GBM Using IA carboplatin in GBM relapse, a response in 70% of patients, and a 22 months overall survival + an increase in PFS to 5 months has been observed. This ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4740000/

Concurrent therapy to enhance radiotherapeutic outcomes in ... The 1- and 2-year survival rates were 58% and 31%, respectively. These promising findings led way to large multi-institutional phase III cooperative group trial ...