COG ARAR 2331 Prospective Treatment of Types I, II, and III Pleuropulmonary Blastoma (PPB)

THIS PROTOCOL IS FOR RESEARCH PURPOSES ONLY, SEE PAGE 1 FOR USAGE POLICY ARAR2331 The Children''s Oncology Group has received a Certificate of Confidentiality from the federal government, which will help us protect the privacy of our research subjects. The Certificate protects against the involuntary release of information about your subjects collected during the course of our covered studies. The researchers involved in the studies cannot be forced to disclose the identity or any information collected in the study in any legal proceedings at the federal, state, or local level, regardless of whether they are criminal, administrative, or legislative proceedings. However, the subject or the researcher may choose to voluntarily disclose the protected information under certain circumstances. For example, if the subject or his/her guardian requests the release of information in writing, the Certificate does not protect against that voluntary disclosure. Furthermore, federal agencies may review our records under limited circumstances, such as a DHHS request for information for an audit or program evaluation or an FDA request under the Food, Drug and Cosmetics Act. The Certificate of Confidentiality will not protect against mandatory disclosure by the researchers of information on suspected child abuse, reportable communicable diseases, and/or possible threat of harm to self or others. ABSTRACT PPB is the most common malignant lung tumor of infancy and early childhood. More than 90% of clinically significant PPB occurs in children under the age of seven. PPB is unique among solid tumors in that it progresses through three distinct histopathologic types, from purely cystic (Type I), to mixed cystic and solid (Type II), to purely solid sarcoma (Type III). A fourth type of PPB, Type Ir (regressed) PPB, which lacks malignant cells, is also recognized. Type I PPB is most commonly diagnosed in infants (median age 7 months); 95% of children with Type I PPB are under 2.5 years of age. Types II and III PPB are diagnosed at a median age of 35 and 39 months, respectively. Despite intensive chemotherapy, 3-year EFS is 66.2% (95% CI: 55.3, 79.3) and OS 84.6% (95% CI: 75.7, 94.5) for children with Type II PPB, and 3-year EFS is only 56.1% (95% CI: 43.7, 71.9) and OS 62.2% (95% CI: 49.3, 78.6) for Type III PPB. Local recurrence within the thorax is the most common first failure event. As the CNS is the most common extra-thoracic site of treatment failure, integration of agents with established CNS penetration is also of high importance. Preclinical and some clinical data suggest that camptothecins may be effective in the treatment of PPB. In this trial, we will assess the overall response to two cycles of window therapy using vincristine, topotecan, and cyclophosphamide (VTC) for children with Types II and III PPB. Additionally, we will estimate progression-free survival (PFS) and overall survival (OS) when integrating camptothecins into standard care therapy. In this study, we’ll assess PFS and OS in children with Type I and Ir PPB following resection and refine the indications for chemotherapy using prospectively defined criteria for adjuvant treatment. Children younger than age five with Type I PPB with less than R0 following best resection or residual, unresectable cysts greater than or equal to one cm in size will receive VAC/VA chemotherapy, while the remaining children will be observed. Correlative biology studies will also be performed. Version Date: 03/03/2025 Page 8