Carboplatin Regimens for Brain Tumors

Not currently recruiting at 22 trial locations

Overseen By Laura Kane

Age: < 65

Sex: Any

Trial Phase: Phase 3

Sponsor: Alicia Lenzen

Must not be taking: Investigational agents

Disqualifiers: Subependymal Giant Cell Astrocytomas, intrinsic brainstem tumors, 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: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether the chemotherapy drug carboplatin alone can treat low-grade glioma (a type of brain tumor) as effectively as the usual combination of carboplatin and vincristine. The goal is to determine if carboplatin alone can maintain treatment success while improving the quality of life for patients and their families. This trial focuses on individuals under 21 with a low-grade glioma who have not started other treatments besides surgery or steroids. As a Phase 3 trial, it represents the final step before FDA approval, offering patients a chance to contribute to potentially groundbreaking treatment advancements.

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 cannot be on any other investigational or chemotherapy drugs. If you are taking those, you would need to stop.

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

Research has shown that carboplatin, whether used alone or with vincristine, is generally safe, though side effects can occur. In studies where carboplatin was combined with vincristine to treat children with low-grade brain tumors, many patients experienced positive outcomes. However, some faced side effects like low blood cell counts, increasing the risk of infections or bruising.

Carboplatin alone has also been studied for various brain tumors. It is considered somewhat effective and generally safe, but like many cancer treatments, it can cause side effects, such as changes in blood cell levels. Doctors closely monitor this during treatment.

Both treatments have been tested in many patients, and while side effects can occur, they are usually manageable. It's important to discuss with a healthcare provider what to expect and how to handle any possible side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for brain tumors because they offer unique approaches compared to traditional options. The combination of Carboplatin and Vincristine provides an aggressive regimen with a structured induction and maintenance phase, potentially increasing efficacy through its dual-drug strategy. On the other hand, the Carboplatin-alone treatment delivers a higher dosage less frequently, which might reduce side effects and improve patient quality of life. Both approaches aim to target cancer cells more effectively and could lead to better outcomes for patients.

What evidence suggests that carboplatin alone could be an effective treatment for low grade glioma?

Research has shown that using carboplatin and vincristine together effectively treats low-grade gliomas, a type of brain tumor, in children. This combination excels at controlling these tumors and improving survival rates. In this trial, one group of participants will receive this combination treatment. Another group will receive carboplatin alone, which has also shown promise, as studies indicate it can manage these tumors well. Early results suggest that carboplatin alone might be as effective as the combination treatment. Both approaches in this trial aim to manage the condition effectively, with ongoing research to understand their effects on quality of life. ^{1 4 5 6 7}

Who Is on the Research Team?

Alicia Lenzen, MD

Principal Investigator

Attending

Are You a Good Fit for This Trial?

This trial is for children and young adults under 21 with low grade glioma brain tumors who haven't had previous tumor treatment, except surgery or steroids. They must be in stable condition, have normal organ function, not be pregnant or breastfeeding, and willing to use birth control.

Inclusion Criteria

I can do most daily activities by myself.

Patients of childbearing or child fathering potential must be willing to use a medically acceptable form of birth control, which includes abstinence, while being treated on this study and for 6 months after the last drug administration.

My seizures are under control.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction Treatment

Participants receive 10 weeks of Carboplatin and Vincristine therapy

10 weeks

Weekly visits for IV infusion

Maintenance Treatment

Maintenance consists of 8 cycles of chemotherapy, each lasting 6 weeks

48 weeks

Weekly visits for IV infusion during each cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 years

What Are the Treatments Tested in This Trial?

Interventions

• Carboplatin
• Vincristine

Trial Overview The study compares two treatments: the standard therapy of carboplatin plus vincristine versus just carboplatin alone. It aims to see if carboplatin by itself can effectively treat low grade gliomas while possibly improving patients' quality of life.

How Is the Trial Designed?

Group I: Carboplatin alone Experimental Treatment 2 Interventions

Carboplatin is given once every four weeks, Each 4-week period is considered a cycle. Regimen B will last for 13 cycles which is equivalent to one year (52 weeks). Carboplatin 560 mg/m2 (or 19 mg/kg for children weighing less than 12 kg) IV over 1 hour every 4 weeks

Group II: Carboplatine and Vincristine Active Control 2 Interventions

Induction: 10 weeks of Carboplatin and Vincristine therapy. Carboplatin 175 mg/m2 give an an IV infusion weeks 1, 2, 3, 4, 7, 8, 9, 10. Vincristine 1.5mg/m2 (0.05 mg/kg if child less than 12 kg) (maximum dose 2.0 mg) give as an IV bolus infusion on weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10. Maintenance: Maintenance consists of 8, 6-week cycles of chemotherapy. It begins week 12 of Induction or when peripheral counts recover with ANC \>1,000/µL and platelet count \>100,000/µL. Each cycle will consist of 4 weekly doses of carboplatin, three weekly doses of vincristine (given concomitantly with the first 3 weeks of carboplatin), followed by two weeks of rest for a total of 6 weeks. Maintenance will continue for a total of 8 cycles. Carboplatin 175 mg/m2 as an IV continuous infusion over 60 minutes on Week 1, 2, 3, 4 of each cycle. Vincristine 1.5 mg/m2 (0.05 mg/ kg for children \<12 kg) (maximum dose 2.0 mg) IV bolus infusion on Week 1, 2, 3 of each cycle.

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?

Alicia Lenzen

Lead Sponsor

Trials

1

Recruited

100+

Natasha Pillay Smiley

Lead Sponsor

Trials

1

Recruited

100+

Published Research Related to This Trial

In a Phase II trial involving 95 children with recurrent brain tumors, carboplatin showed some efficacy, particularly in medulloblastoma and central nervous system PNET, with a notable response rate in patients who had not previously been treated with cisplatin.

The treatment was associated with significant side effects, including low neutrophil and platelet counts in a substantial number of patients, but it did not cause nephrotoxicity, indicating a relatively safer profile in that regard.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carboplatin in childhood brain tumors. A Children's Cancer Study Group Phase II trial. Gaynon, PS., Ettinger, LJ., Baum, ES., et al.[2019]

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 study of patients with advanced non-small cell lung cancer receiving carboplatin and nanoparticle albumin-bound paclitaxel, 55% experienced treatment suspension, primarily due to neutropenia (65.2%) and infections (24.2%).

Baseline liver dysfunction, age 65 or older, and a performance status of 2 were identified as significant risk factors for treatment suspension, highlighting the need for careful monitoring in these patient groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of risk factors associated with carboplatin and nab-paclitaxel treatment suspension in patients with non-small cell lung cancer. Saito, Y., Takekuma, Y., Shinagawa, N., et al.[2022]

Carboplatin is a less toxic alternative to cisplatin, allowing for comparable antitumor doses with reduced side effects, particularly in terms of nephrotoxicity and severity of nausea and vomiting.

In phase I studies involving various adult and pediatric cancers, carboplatin showed objective responses while primarily causing reversible myelosuppression, with recommended dosing strategies established for further clinical evaluation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Results of NCI-sponsored phase I trials with carboplatin. Foster, BJ., Clagett-Carr, K., Leyland-Jones, B., et al.[2019]

In a study of 41 patients with advanced cervical cancer receiving carboplatin, the overall response rate was 15%, indicating modest efficacy with two complete and four partial responses.

Carboplatin had a more favorable toxicity profile compared to cisplatin, with major side effects including nausea (48%), anemia (47%), and leukopenia (38%), suggesting it may be a safer option for further exploration in treatment regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II trial of carboplatin for recurrent or metastatic squamous carcinoma of the uterine cervix: a Southwest Oncology Group study. Weiss, GR., Green, S., Hannigan, EV., et al.[2019]

A phase 1 trial involving 26 children with low-grade gliomas tested two schedules of carboplatin and vinblastine, revealing that Schedule A was not feasible due to high rates of neutropenia, while Schedule B showed a more tolerable safety profile at a carboplatin dose of 400 mg/m².

The combination treatment on Schedule B resulted in 1 partial response and 6 minor responses among evaluable patients, with notable improvements in vision for 7 out of 9 patients with visual pathway tumors, suggesting potential efficacy and warranting further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase 1 study of vinblastine in combination with carboplatin for children with low-grade gliomas: a Children's Oncology Group phase 1 consortium study. Jakacki, RI., Bouffet, E., Adamson, PC., et al.[2021]

In a Phase II study involving 117 children with drug-resistant solid tumors, carboplatin showed some effectiveness, particularly against Wilms' tumor, Ewing's sarcoma, neuroblastoma, soft tissue sarcoma, and endodermal sinus tumor of the testis.

While myelosuppression (low blood cell counts) was common, carboplatin exhibited low rates of nonhematologic toxicity, such as ototoxicity and nephrotoxicity, making it a potentially safer option compared to its parent compound, cisplatin.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II study of carboplatin in children with recurrent or progressive solid tumors. A report from the Childrens Cancer Group. Ettinger, LJ., Gaynon, PS., Krailo, MD., et al.[2019]

In a Phase I study involving 15 patients with various brain tumors, intracarotid carboplatin showed some efficacy, with one patient experiencing partial remission and others showing stable disease, although the median survival was only 9 weeks.

The treatment was associated with mild to moderate nausea and some hematological side effects, but severe complications occurred in patients with pre-existing vascular issues, highlighting the need for careful patient selection and monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I study of intracarotid administration of carboplatin. Stewart, DJ., Belanger, JM., Grahovac, Z., et al.[2019]

In a study of 70 patients with inoperable non-small cell lung cancer (NSCLC), carboplatin alone showed a 16% overall response rate with an acceptable safety profile, indicating its potential as a treatment option.

Combination therapies involving carboplatin with other drugs like etoposide and vinblastine yielded response rates of 11%, 12%, and 20%, respectively, but with increased toxicity, particularly myelosuppression, highlighting the need to balance efficacy and safety in treatment plans.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carboplatin in non-small cell lung cancer: an update on the Cancer and Leukemia Group B experience. Green, MR., Kreisman, H., Doll, DC., et al.[2018]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3499591/

Carboplatin and bevacizumab for recurrent malignant glioma Carboplatin monotherapy has been shown to be modestly effective in therapy of recurrent malignant glioma (5,18). The results of combination therapies utilizing ...

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. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12217717/

Paclitaxel and Carboplatin in Combination with Low-Intensity ... We recently reported on clinical trials for patients with recurrent glioblastoma where low-intensity pulsed ultrasound and microbubbles ...

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

Carboplatin Regimens for Brain Tumors · Info for Participants Carboplatin, when used alone or with vincristine, has shown effectiveness in treating low-grade gliomas (a type of brain tumor) in children, with a significant ...

5. 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 ...

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

Repeated blood–brain barrier opening with a nine-emitter ... In the 12 patients who received carboplatin just prior to sonication, the progression-free survival was 3.1 months, the 1-year overall survival ...

7. mdpi.com mdpi.com/2077-0383/14/2/524

Safety of Cerebral Intra-Arterial Chemotherapy for the ... Specifically, for carboplatin, the IA + BBBD combination further increased delivery by an 18-fold factor compared to IA alone and a 320-fold factor compared to ...