Surgery + Chemotherapy for Pleuropulmonary Blastoma

Recruiting at 46 trial locations

Overseen By Alberto S. Pappo

Age: < 65

Sex: Any

Trial Phase: Phase 3

Sponsor: Children's Oncology Group

Must not be taking: Antiretrovirals

Disqualifiers: Prior chemotherapy, Charcot-Marie-Tooth, pregnancy, 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: 3

110 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, if you are HIV-infected, you must not be on anti-retroviral agents that strongly affect the enzyme CYP3A4. It's best to discuss your current medications with the trial team.

Is the combination of surgery and chemotherapy safe for treating pleuropulmonary blastoma?

The safety of surgery combined with chemotherapy for pleuropulmonary blastoma has been explored in various cases. Chemotherapy drugs like vincristine, actinomycin-D, and cyclophosphamide have been used in children with some success, but the overall safety profile is not well-documented, and the treatment can be intensive. ^{1 2 3 4 5}

How does the treatment for Pleuropulmonary Blastoma differ from other treatments?

The treatment for Pleuropulmonary Blastoma involving surgery and chemotherapy is unique because it combines surgical removal of the tumor with chemotherapy, which may include drugs like topotecan. Topotecan is known for its ability to inhibit topoisomerase I, an enzyme important for DNA replication, and has been studied in various cancers, showing potential benefits in stabilizing disease and improving symptoms. ^{6 7 8 9 10}

What is the purpose of this trial?

This phase III trial tests how well surgery plus chemotherapy compared to surgery alone works in treating patients with type I pleuropulmonary blastoma (PPB), and tests how well surgery plus standard chemotherapy with the addition of topotecan works compared to surgery plus standard chemotherapy alone in treating patients with type II and III PPB. Historically, most children with type I PPB had surgery and approximately 40% of children with type I PPB received chemotherapy following their surgery, usually for 22-42 weeks. There has not been a consistent standard for which children with type I PPB receive chemotherapy after surgery. For patients whose tumor has been removed completely with surgery, observation without chemotherapy may work as well as giving chemotherapy after surgery in preventing a return of the PPB tumor. The standard chemotherapy for patients with types II or III PPB in the United States is four cycles of IVADo (ifosfamide, vincristine, dactinomycin, and doxorubicin) followed by 8 cycles of IVA (ifosfamide, vincristine and dactinomycin). Ifosfamide is in a class of medications called alkylating agents. It works by slowing or stopping the growth of tumor cells in the body. Vincristine is in a class of medications called vinca alkaloids. It works by stopping tumor cells from growing and dividing and may kill them. Dactinomycin is a type of antibiotic that is only used in cancer chemotherapy (antineoplastic antibiotic). It works by damaging the cell's deoxyribonucleic acid (DNA) and may kill tumor cells. Doxorubicin is in a class of medications called anthracyclines. Doxorubicin damages the cell's DNA and may kill tumor cells. It also blocks a certain enzyme needed for cell division and DNA repair. Topotecan is in a class of medications called topoisomerase I inhibitors. It works by interfering with tumor cell DNA which kills them. Giving topotecan in addition to standard IVADo and IVA chemotherapy regimens may shrink the cancer as well as or better than the standard therapy or could decrease the chance the tumor spreads while causing fewer side effects.

Research Team

Kris Ann P Schultz

Principal Investigator

Children's Oncology Group

Eligibility Criteria

This trial is for children and young adults (up to 21 years old) diagnosed with Type I, Ir, II or III Pleuropulmonary Blastoma (PPB), a rare type of lung cancer. Participants must have been diagnosed within the last 60 days. Those with certain genetic variants may join without biopsy if it's unsafe. Kidney function needs to be within specific limits based on age.

Inclusion Criteria

I am between 1 month and less than 6 months old with a creatinine level at or below 0.4 mg/dL.

I am 21 years old or younger.

I am between 6 and 10 years old with a creatinine level of 1 or less.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Surgery

Patients undergo surgery for tumor removal, with observation or chemotherapy following based on tumor type and resection status

Varies based on individual treatment plan

Chemotherapy

Patients receive chemotherapy regimens based on tumor type: VAC1200/VA for Type I, VTC400 followed by IVADo and IVA for Types II/III

Up to 42 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 5 years

Every 3 months for 24 months, then every 6 months until 5 years

Treatment Details

Interventions

• Topotecan

Trial Overview The study tests surgery plus chemotherapy versus surgery alone for Type I PPB patients. For Types II and III PPB, it compares standard chemo (IVADo/IVA) with or without an additional drug called Topotecan. The goal is to see if adding Topotecan can better shrink tumors or prevent spread with fewer side effects.

Participant Groups

Group I: Group II, Arm 4 (VTC400, IVADo, IVA regimens) Experimental Treatment 14 Interventions

See Detailed Description for Group II, Arm 4.

Group II: Group II, Arm 3 (VTC400, IVADo, VTC250, VAC1200 regimens) Experimental Treatment 14 Interventions

See Detailed Description for Group II, Arm 3.

Group III: Group I, Arm 1 (VAC1200/VA regimen) Experimental Treatment 6 Interventions

Patients receive vincristine IV on days 1, 8, and 15 of cycles 1-3 and 5-7, dactinomycin IV over 1-5 or 10-15 minutes on day 1 of each cycle, and cyclophosphamide IV over 30-60 minutes on day 1 of cycles 1-4. Cycles repeat every 21 days for 8 cycles in the absence of disease progression or unacceptable toxicity. Tumor tissue is collected and centrally reviewed by a study pathologist. Patients also undergo blood sample collection, CT and ultrasound throughout the study.

Group IV: Group I, Arm 2 (observation) Active Control 4 Interventions

Patients undergo observation on study. This includes tumor tissue collection and review by a study pathologist, and blood sample collection, chest CT, and ultrasound throughout the study.

Who Is Running the Clinical Trial?

Children's Oncology Group

Lead Sponsor

Trials

467

Recruited

241,000+

Findings from Research

The maximum-tolerated dose (MTD) of Topotecan when combined with full-dose thoracic radiotherapy is determined to be 0.4 mg/m² per day, based on observed dose-limiting toxicities such as severe diarrhea and hematological issues.

In a study involving 24 patients with advanced thoracic malignancies, the treatment resulted in nine partial responses and significant local tumor responses, suggesting that Topotecan may enhance the effectiveness of radiotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I study of Topotecan, as a radiosensitizer, for thoracic malignancies. Forouzannia, A., Schiller, J., Berlin, J., et al.[2019]

In a phase III study involving 795 patients with extensive disease small-cell lung cancer, the combination of topotecan and cisplatin (TP) demonstrated noninferior overall survival compared to cisplatin and etoposide (PE), with median survival times of 44.9 weeks for TP and 40.9 weeks for PE.

TP showed superior efficacy in terms of overall response rates (55.5% for TP vs. 45.5% for PE) and longer median time to progression (27.4 weeks for TP vs. 24.3 weeks for PE), but it also had a slightly higher incidence of hematologic toxicities, making it unsuitable as a first-line treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Topotecan/cisplatin compared with cisplatin/etoposide as first-line treatment for patients with extensive disease small-cell lung cancer: final results of a randomized phase III trial. Fink, TH., Huber, RM., Heigener, DF., et al.[2013]

References

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

Case report: pulmonary blastoma in children--response to chemotherapy. [2015]

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

Survival with combined modality therapy after intracerebral recurrence of pleuropulmonary blastoma. [2019]

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

A Case of Biphasic Pulmonary Blastoma Treated with Carboplatin and Paclitaxel plus Bevacizumab. [2020]

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

Pleuropulmonary blastoma: long-term survival and literature review. [2019]

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

Role of chemotherapy in pediatric pulmonary blastoma. [2019]

6. Ireland pubmed.ncbi.nlm.nih.gov

A phase I study of Topotecan, as a radiosensitizer, for thoracic malignancies. [2019]

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

Topotecan/cisplatin compared with cisplatin/etoposide as first-line treatment for patients with extensive disease small-cell lung cancer: final results of a randomized phase III trial. [2013]

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

Phase II study of oral topotecan in advanced non-small cell lung cancer. [2013]

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

Topotecan in pediatric patients with recurrent and progressive solid tumors: a Pediatric Oncology Group phase II study. [2022]

10. Switzerland pubmed.ncbi.nlm.nih.gov

Topotecan plus Platinum-Based Chemotherapy versus Etoposide plus Platinum-Based Chemotherapy for Small-Cell Lung Cancer: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. [2021]