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.
21 years of age or younger
Newly diagnosed PPB. Note that patients with known germline DICER1 variant or mosaicism with a large, solid unresectable thoracic mass with imaging features characteristic for Type II or III PPB are eligible without histologic confirmation of the diagnosis if a biopsy of the mass is not considered safe or feasible
Individuals are eligible based on institutional diagnosis of Type I, Ir, II or III PPB diagnosed within 60 days prior to enrollment. Children with Type II or III PPB at risk for clinical decompensation may receive protocol therapy while awaiting rapid central pathology review. Children with Type I or Ir PPB will be assigned to chemotherapy vs. observation based on imaging and central pathology review diagnosis. Type I and Ir patients should not begin chemotherapy prior to return of central pathology results
Age: 1 month to < 6 months - Maximum Serum Creatinine (mg/dL): 0.4 (Male), 0.4 (Female)
Administration of prior PPB-directed chemotherapy is an exclusion criterion. Prior treatment for another malignancy is not an exclusion criterion
Patients with known Charcot-Marie-Tooth disease
Female patients who are pregnant since fetal toxicities and teratogenic effects have been noted for several of the study drugs. A pregnancy test is required for female patients of childbearing potential
Lactating females who plan to breastfeed their infants
Sequential
Biospecimen Collection
Procedure/SurgeryUndergo collection of blood samples
Biospecimen Collection
Procedure/SurgeryTumor tissue is collected and centrally reviewed by a study pathologist
Bone Scan
Procedure/SurgeryUndergo bone scan
Computed Tomography
Procedure/SurgeryUndergo CT
Cyclophosphamide
DrugGiven IV
Dactinomycin
Biological/VaccineGiven IV
Dexrazoxane
DrugGiven IV
Doxorubicin
DrugGiven IV
Echocardiography Test
Procedure/SurgeryUndergo ECHO
Ifosfamide
DrugGiven IV
Magnetic Resonance Imaging
Procedure/SurgeryUndergo MRI
Multigated Acquisition Scan
Procedure/SurgeryUndergo MUGA
Patient Observation
Other interventionUndergo observation
Positron Emission Tomography
Procedure/SurgeryUndergo PET
Topotecan
DrugGiven IV
Ultrasound Imaging
Procedure/SurgeryUndergo ultrasound
Vincristine
DrugGiven IV
Objective response
Response rates at the end of Cycle 2 will be calculated as the percent of evaluable patients who are responders, and confidence intervals will be constructed using the Wilson score interval method. Any eligible type II/III patients who do not undergo complete resection, have measurable disease at baseline (per central review) and start protocol therapy will be included in the primary analysis.
Progression-free survival (PFS) in children with Types II and III pleuropulmonary blastoma (PPB)
3-year PFS, along with the confidence intervals will be estimated using the Kaplan-Meier method. These results will be presented for Type II and III patients combined regardless of the timing of surgery.
Overall survival (OS) in children with Types II and III PPB
3-year OS, along with the confidence intervals will be estimated using the Kaplan-Meier method. These results will be presented for Type II and III patients combined regardless of the timing of surgery.
PFS in children with Types I PPB
3-year PFS, along with the confidence intervals will be estimated using the Kaplan-Meier method.
OS in children with Types I PPB
3-year OS, along with the confidence intervals will be estimated using the Kaplan-Meier method.
Resection rates for Type I PPB
Will be reported based on central radiology reviews.
Resection rates for Type II and III PPB
Will be reported based on central radiology reviews.
Resection rates for Type II and III PPB
Will be reported based on central radiology reviews.
Incidence of surgery-related adverse events
Percentage of patients with surgery related adverse event. Results will be summarized separately for those undergoing primary resection versus those undergoing biopsy followed by neoadjuvant chemotherapy.
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