Carboplatin Regimens for Brain Tumors

Recruiting at 20 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

95 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the drug carboplatin for brain tumors?

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 number of patients achieving tumor stabilization or better outcomes. Additionally, carboplatin has been used successfully in treating other cancers, like non-small cell lung cancer, indicating its potential effectiveness in cancer treatment. ^{1 2 3 4 5}

Is carboplatin safe for use in humans?

Carboplatin has been tested in various clinical trials and is generally considered safe for use in humans, though it can cause side effects like low blood cell counts, nausea, vomiting, and hearing issues. It is less likely to cause kidney damage and severe nausea compared to a similar drug, cisplatin. ^{2 6 7 8 9}

How is the drug Carboplatin, used with Vincristine, unique for treating brain tumors?

This drug combination is unique because Carboplatin is less toxic than similar drugs and has shown effectiveness in treating pediatric brain tumors, while Vincristine adds to its effectiveness. The combination aims to reduce side effects and improve outcomes, especially in children with low-grade gliomas. ^{10 11 12 13 14}

What is the purpose of this trial?

This study is trying to learn and understand if the chemotherapy drug called carboplatin works as well as the standard therapy. The standard therapy for Low Grade Glioma (LGG) in children and young adults is using a combination of carboplatin and vincristine. Studies in children have shown that the use of carboplatin alone has promise of being just as effective for treating LGG as standard therapy. Additionally, this study will try to understand if treatment with carboplatin alone is associated with an improved quality of life for LGG patients and their families.

Research Team

Alicia Lenzen, MD

Principal Investigator

Attending

Eligibility Criteria

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.

My seizures are under control.

I am not pregnant or breastfeeding and have a negative pregnancy test.

Timeline

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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]

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 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]

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]

References

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

Phase I study of intracarotid administration of carboplatin. [2019]

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

Nonrandomized comparison of neurofibromatosis type 1 and non-neurofibromatosis type 1 children who received carboplatin and vincristine for progressive low-grade glioma: A report from the Children's Oncology Group. [2021]

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

Carboplatin and vincristine for recurrent and newly diagnosed low-grade gliomas of childhood. [2017]

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

Single agent carboplatin for pediatric low-grade glioma: A retrospective analysis shows equivalent efficacy to multiagent chemotherapy. [2016]

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

Carboplatin in non-small cell lung cancer: an update on the Cancer and Leukemia Group B experience. [2018]

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

Carboplatin in childhood brain tumors. A Children's Cancer Study Group Phase II trial. [2019]

7. Germany 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. [2022]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Results of NCI-sponsored phase I trials with carboplatin. [2019]

9. United States 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. [2019]

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

Carboplatin and recurrent childhood brain tumors. [2017]

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

Carboplatin-based primary chemotherapy for infants and young children with CNS tumors. [2021]

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

Toxicity and efficacy of carboplatin and etoposide in conjunction with disruption of the blood-brain tumor barrier in the treatment of intracranial neoplasms. [2019]

13. United States 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. [2019]

14. England 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. [2021]