Surgery + Chemotherapy for Pleuropulmonary Blastoma

Recruiting at 69 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine the effectiveness of combining surgery with chemotherapy compared to surgery alone in treating pleuropulmonary blastoma (PPB), a rare childhood lung cancer. It will also assess whether adding topotecan, a chemotherapy drug, to the standard chemotherapy enhances treatment effectiveness for more severe types of PPB. Children with newly diagnosed PPB, especially those with a large, solid mass in the chest, may be suitable for this trial if they have not received prior chemotherapy for PPB. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the opportunity to contribute to potentially groundbreaking treatment advancements.

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

Research has shown that the chemotherapy treatment for pleuropulmonary blastoma (PPB) in children, which includes vincristine, dactinomycin, and cyclophosphamide, has achieved some success. Although the exact safety details remain unclear, these drugs are commonly used in similar contexts. Another treatment option, IVADo, which includes ifosfamide, vincristine, dactinomycin, and doxorubicin, has demonstrated results as good as or better than previous treatments for types II and III PPB, suggesting these treatments are generally well-tolerated.

Studies indicate that adding topotecan to the treatment plan may help shrink the cancer and reduce the chance of it spreading. While topotecan is used in other cancer treatments, its safety in this specific context is still under investigation, though it is believed to have manageable side effects.

Overall, despite the risks associated with chemotherapy for PPB, the treatments used in this trial have been part of standard care and possess a known safety record. The ongoing study aims to provide more information on the safety of these treatments. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Most treatments for pleuropulmonary blastoma involve surgery and chemotherapy with drugs like vincristine, dactinomycin, and cyclophosphamide. But researchers are exploring something new and exciting with the addition of topotecan. Unlike the standard chemotherapy, topotecan works by blocking a specific enzyme needed for cancer cells to replicate their DNA, potentially leading to more effective cancer cell death. This unique mechanism could make it a powerful addition to current treatments, offering hope for better outcomes in patients.

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

This trial will compare different treatment approaches for pleuropulmonary blastoma (PPB). Studies have shown that surgery, either alone or with chemotherapy, can effectively treat PPB. For more advanced types of PPB, known as type II and III, a specific chemotherapy plan called the IVADo regimen—which includes ifosfamide, vincristine, dactinomycin, and doxorubicin—has delivered similar or better results compared to older treatments. In this trial, some participants will receive the IVADo regimen, and adding topotecan might enhance its effectiveness by targeting the cancer cell's DNA, potentially shrinking the tumor more effectively. For type I PPB, the situation is less clear, as some patients do well with just surgery and no chemotherapy. Overall, combining surgery and chemotherapy has shown promise, especially for the more severe types of PPB. ^{5 6 7 8 9}

Who Is on the Research Team?

Kris Ann P Schultz

Principal Investigator

Children's Oncology Group

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

Citations

1.

mdpi.com

mdpi.com/2072-6694/17/19/3223

Pleuropulmonary Blastoma in Children: A Nationwide ...

The aim of the study was to analyze the treatment of pleuropulmonary blastoma (PPB) in a group of 15 pediatric patients, with a median age of 39 months.

2.

clinicaltrials.gov

clinicaltrials.gov/study/NCT06647953?term=ARAR2331&rank=1

Testing a Standardized Approach to Surgery and ...

This phase III trial tests how well surgery plus chemotherapy compared to surgery alone works in treating patients with type I pleuropulmonary blastoma ...

3.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC9901992/

A Report From the International PPB/DICER1 Registry - PMC

In the largest published study of types II and III, the 5-year overall survival (OS) was 71% and 53%, respectively; this cohort received various ...

4.

oncologynurseadvisor.com

oncologynurseadvisor.com/news/ivado-regimen-pleuro-pulmonary-blastoma-event-free-overall-survival/

Regimen Offers Hope for Children with Type II and III ...

Outcomes for children with type II and type III pleuropulmonary blastoma (PPB) was similar to improved compared with an historical control ...

5.

clinicaltrial.be

clinicaltrial.be/en/details/12882?per_page=20&only_recruiting=0&only_eligible=0&only_active=0

International Pleuropulmonary Blastoma (PPB) Treatment ...

If chemotherapy is used the Registry will suggest that it be combination chemotherapy with vincristine, dactinomycin, cyclophosphamide (VAC ).

6.

clinicaltrials.gov

clinicaltrials.gov/study/NCT01464606

International Pleuropulmonary Blastoma (PPB) Treatment ...

If chemotherapy is used the Registry will suggest that it be combination chemotherapy with vincristine, dactinomycin, cyclophosphamide (VAC ). For Types II and ...

7.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC12523366/

Pleuropulmonary Blastoma in Children - PubMed Central - NIH

The 5-year overall survival (OS) rates vary, with type IR showing the most favorable prognosis, at 100%, followed by type I, at 98%. For type II ...

8.

researchgate.net

researchgate.net/publication/355333448_Phase_III_Trial_Adding_Vincristine-Topotecan-Cyclophosphamide_to_the_Initial_Treatment_of_Patients_With_Nonmetastatic_Ewing_Sarcoma_A_Children's_Oncology_Group_Report

(PDF) Phase III Trial Adding Vincristine-Topotecan ...

The 5-year EFS and OS were 78% and 87%, respectively. There was no difference in survival outcomes between randomized groups (5-year EFS regimen ...

9.

withpower.com

withpower.com/trial/phase-3-pulmonary-blastoma-11-2024-33833

Surgery + Chemotherapy for Pleuropulmonary Blastoma

Chemotherapy drugs like vincristine, actinomycin-D, and cyclophosphamide have been used in children with some success, but the overall safety profile is not ...