Pleuropulmonary BlastomaPhase 3NCT06647953
Testing a Standardized Approach to Surgery and Chemotherapy for Type I Pleuropulmonary Blastoma or the Addition of an Anti-cancer Drug, Topotecan, to the Usual Treatment for Types II and III Pleuropulmonary Blastoma
A Phase 3 study testing Biospecimen Collection, Bone Scan and Computed Tomography in people with Pleuropulmonary Blastoma, run by Children's Oncology Group at 87 sites in 2 countries.
Trial summary
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… Read more about this study
- Who is it for?
- Ages Up to 21 years
- Conditions the study is for
- Pleuropulmonary Blastoma
- What is being tested?
- Biospecimen Collection, Bone Scan and Computed Tomography
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 110 participants
- Where
- 87 sitesin 2 countries
- Study dates
- 21 Mar 2025to 31 Mar 2029
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 21 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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
- For patients with Type II or III PPB (within 7 days prior to enrollment): A serum creatinine based on age/sex as follows:
- Age: 1 month to < 6 months - Maximum Serum Creatinine (mg/dL): 0.4 (Male), 0.4 (Female)
- Age: 6 months to < 1 year - Maximum Serum Creatinine (mg/dL): 0.5 (Male), 0.5 (Female)
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- Age: 1 to < 2 years - Maximum Serum Creatinine (mg/dL): 0.6 (Male), 0.6 (Female)
- Age: 2 to < 6 years - Maximum Serum Creatinine (mg/dL): 0.8 (Male), 0.8 (Female)
- Age: 6 to < 10 years - Maximum Serum Creatinine (mg/dL): 1 (Male), 1 (Female)
- Age: 10 to < 13 years - Maximum Serum Creatinine (mg/dL): 1.2 (Male), 1.2 (Female)
- Age: 13 to < 16 years - Maximum Serum Creatinine (mg/dL): 1.5 (Male), 1.4 (Female)
- Age: ≥ 16 years - Maximum Serum Creatinine (mg/dL): 1.7 (Male), 1.4 (Female) OR - A 24 hour urine creatinine clearance ≥ 60 mL/min/1.73 m^2 OR - A glomerular filtration rate (GFR) ≥ 60 mL/min/1.73 m^2. GFR must be performed using direct measurement with a nuclear blood sampling method OR direct small molecule clearance method (iothalamate or other molecule per institutional standard)
- Note: Estimated GFR (eGFR) from serum creatinine, cystatin C or other estimates are not acceptable for determining eligibility
- For patients with Type II or III PPB (within 7 days prior to enrollment): Total bilirubin ≤ 1.5 x upper limit of normal (ULN) for age
- For patients with Type II or III PPB (within 7 days prior to enrollment): Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) ≤ 135 U/L
- Note: For the purpose of this study, the ULN for SGPT (ALT) has been set to the value of 45 U/L
- Shortening fraction of ≥ 27% by echocardiogram, or ejection fraction of ≥ 50% by radionuclide angiogram (within 21 days prior to start of protocol therapy)
- HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible as long as they are NOT receiving anti-retroviral agents that are strong inhibitors or inducers of CYP3A4
Who cannot join
- 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
- Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their study participation
- All patients and/or their parents or legal guardians must sign a written informed consent
- All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met
Trial locations and contacts
87 sites in 2 countries. Contact the study team or a site near you to ask about taking part.
87 sites in 2 countries
United States80 sites, 80 recruiting
- Recruiting
Albany Medical Center
Albany, New York, 12208
Site Public Contact, 518-262-5513
Lauren R. Weintraub
- Recruiting
C S Mott Children's Hospital
Ann Arbor, Michigan, 48109
Site Public Contact, 800-865-1125
Rama Jasty
- Recruiting
Children's Healthcare of Atlanta - Arthur M Blank Hospital
Atlanta, Georgia, 30329
Site Public Contact, 404-785-0232, Olivia.Floyd@choa.org
Sarah G. Mitchell
- Recruiting
Children's Hospital Colorado
Aurora, Colorado, 80045
Site Public Contact, 303-764-5056, josh.b.gordon@nsmtp.kp.org
Navin R. Pinto
- Recruiting
Dell Children's Medical Center of Central Texas
Austin, Texas, 78723
Site Public Contact, 512-628-1902, TXAUS-DL-SFCHemonc.research@ascension.org
Shannon M. Cohn
- Recruiting
Johns Hopkins University/Sidney Kimmel Cancer Center
Baltimore, Maryland, 21287
Site Public Contact, 410-955-8804, jhcccro@jhmi.edu
Lindy Zhang
- Recruiting
Children's Hospital of Alabama
Birmingham, Alabama, 35233
Site Public Contact, 205-638-9285, oncologyresearch@peds.uab.edu
Elizabeth D. Alva
- Recruiting
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215
Site Public Contact, 877-442-3324
Junne Kamihara
- Recruiting
UNC Lineberger Comprehensive Cancer Center
Chapel Hill, North Carolina, 27599
Site Public Contact, 877-668-0683, cancerclinicaltrials@med.unc.edu
Thomas B. Alexander
- Recruiting
University of Virginia Cancer Center
Charlottesville, Virginia, 22908
Site Public Contact, 434-243-6303, uvacancertrials@hscmail.mcc.virginia.edu
Brian C. Belyea
- Recruiting
Lurie Children's Hospital-Chicago
Chicago, Illinois, 60611
Site Public Contact, 773-880-4562
Elizabeth A. Sokol
- Recruiting
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, 60637
Site Public Contact, 773-702-8222, cancerclinicaltrials@bsd.uchicago.edu
Lorraine E. Canham
- Recruiting
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229
Site Public Contact, 513-636-2799, cancer@cchmc.org
Brian K. Turpin
- Recruiting
Rainbow Babies and Childrens Hospital
Cleveland, Ohio, 44106
Site Public Contact, 216-844-5437
Duncan S. Stearns
- Recruiting
Nationwide Children's Hospital
Columbus, Ohio, 43205
Site Public Contact, 614-722-6039, Melinda.Triplet@nationwidechildrens.org
Mark A. Ranalli
- Recruiting
UT Southwestern/Simmons Cancer Center-Dallas
Dallas, Texas, 75390
Site Public Contact, 214-648-7097, canceranswerline@UTSouthwestern.edu
Avanthi T. Shah
- Recruiting
Dayton Children's Hospital
Dayton, Ohio, 45404
Site Public Contact, 800-228-4055
Jordan M. Wright
- Recruiting
Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center
Denver, Colorado, 80218
Site Public Contact, 303-832-2344, PSGResearchSharedMailbox@HCAHealthcare.com
Florence Choo
- Recruiting
Children's Hospital of Michigan
Detroit, Michigan, 48201
Site Public Contact, helpdesk@childrensoncologygroup.org
Alissa M. Martin
- Recruiting
Kaiser Permanente Downey Medical Center
Downey, California, 90242
Site Public Contact, 626-564-3455
Robert M. Cooper
- Recruiting
Duke University Medical Center
Durham, North Carolina, 27710
Site Public Contact, 888-275-3853
Jessica M. Sun
- Recruiting
Sanford Broadway Medical Center
Fargo, North Dakota, 58122
Site Public Contact, 701-323-5760, OncologyClinicalTrialsFargo@sanfordhealth.org
Samuel J. Milanovich
- Recruiting
Golisano Children's Hospital of Southwest Florida
Fort Myers, Florida, 33908
Site Public Contact, 239-343-5333, molly.arnstrom@leehealth.org
Emad K. Salman
- Recruiting
Cook Children's Medical Center
Fort Worth, Texas, 76104
Site Public Contact, 682-885-2103, CookChildrensResearch@cookchildrens.org
Kelly L. Vallance
- Recruiting
Corewell Health Grand Rapids Hospitals - Helen DeVos Children's Hospital
Grand Rapids, Michigan, 49503
Site Public Contact, 616-391-1230, crcwm-regulatory@crcwm.org
Kathleen Y. Butler
- Recruiting
Saint Vincent Hospital Cancer Center Green Bay
Green Bay, Wisconsin, 54301
Site Public Contact, 920-433-8889, WI_research_admin@hshs.org
Catherine A. Long
- Recruiting
BI-LO Charities Children's Cancer Center
Greenville, South Carolina, 29605
Site Public Contact, 864-522-4317, Kim.Williams3@prismahealth.org
Aniket Saha
- Recruiting
Riley Hospital for Children
Indianapolis, Indiana, 46202
Site Public Contact, 800-248-1199
Marissa Just
- Recruiting
University of Iowa/Holden Comprehensive Cancer Center
Iowa City, Iowa, 52242
Site Public Contact, 800-237-1225
Andrew P. Groves
- Recruiting
University of Mississippi Medical Center
Jackson, Mississippi, 39216
Site Public Contact, 601-815-6700
Amanda Strobel
- Recruiting
Nemours Children's Clinic-Jacksonville
Jacksonville, Florida, 32207
Site Public Contact, 302-651-5572, Allison.bruce@nemours.org
Sridhi Patel
- Recruiting
Bronson Methodist Hospital
Kalamazoo, Michigan, 49007
Site Public Contact, 616-391-1230, crcwm-regulatory@crcwm.org
Kathleen Y. Butler
- Recruiting
Children's Mercy Hospitals and Clinics
Kansas City, Missouri, 64108
Site Public Contact, 816-302-6808, COGResearchGroup@cmh.edu
Keith J. August
- Not yet recruiting
University of Kentucky/Markey Cancer Center
Lexington, Kentucky, 40536
Site Public Contact, 859-257-3379
James T. Badgett
- Recruiting
Arkansas Children's Hospital
Little Rock, Arkansas, 72202-3591
Site Public Contact, 501-364-7373
Michael W. Bishop
- Recruiting
Loma Linda University Medical Center
Loma Linda, California, 92354
Site Public Contact, 909-558-4050
Albert Kheradpour
- Recruiting
Children's Hospital Los Angeles
Los Angeles, California, 90027
Site Public Contact, 323-361-4110
Rachana Shah
- Recruiting
Norton Children's Hospital
Louisville, Kentucky, 40202
Site Public Contact, 502-629-5500, CancerResource@nortonhealthcare.org
Michael J. Ferguson
- Recruiting
Covenant Children's Hospital
Lubbock, Texas, 79410
Site Public Contact, 806-725-8657, mbisbee@providence.org
Kishor M. Bhende
- Recruiting
Valley Children's Hospital
Madera, California, 93636
Site Public Contact, 559-353-3000, Research@valleychildrens.org
Ruetima Titapiwatanakun
- Recruiting
University of Wisconsin Carbone Cancer Center - University Hospital
Madison, Wisconsin, 53792
Site Public Contact, 800-622-8922, clinicaltrials@cancer.wisc.edu
Margo L. Hoover-Regan
- Recruiting
Saint Jude Children's Research Hospital
Memphis, Tennessee, 38105
Site Public Contact, 888-226-4343, referralinfo@stjude.org
Alberto S. Pappo
- Recruiting
Nicklaus Children's Hospital
Miami, Florida, 33155
Site Public Contact, 888-624-2778
Maggie E. Fader
- Recruiting
Children's Hospitals and Clinics of Minnesota - Minneapolis
Minneapolis, Minnesota, 55404
Site Public Contact, 612-813-5913, pauline.mitby@childrensmn.org
Michael K. Richards
- Recruiting
The Children's Hospital at TriStar Centennial
Nashville, Tennessee, 37203
Site Public Contact, 615-342-1919
Clinton M. Carroll
- Recruiting
Vanderbilt University/Ingram Cancer Center
Nashville, Tennessee, 37232
Site Public Contact, 800-811-8480
Daniel J. Benedetti
- Recruiting
Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital
New Brunswick, New Jersey, 08903
Site Public Contact, 732-235-8675
Scott Moerdler
- Recruiting
The Steven and Alexandra Cohen Children's Medical Center of New York
New Hyde Park, New York, 11040
Site Public Contact, 718-470-3460
Carolyn F. Levy
- Recruiting
Children's Hospital New Orleans
New Orleans, Louisiana, 70118
Site Public Contact, 504-894-5377
Maria C. Velez-Yanguas
- Recruiting
Children's Hospital of The King's Daughters
Norfolk, Virginia, 23507
Site Public Contact, 757-668-7243, CCBDCresearch@chkd.org
Melissa S. Mark
- Recruiting
UCSF Benioff Children's Hospital Oakland
Oakland, California, 94609
Site Public Contact, 510-428-3264, PedOncRschOAK@ucsf.edu
Arun A. Rangaswami
- Recruiting
Kaiser Permanente-Oakland
Oakland, California, 94611
Site Public Contact, 877-642-4691, Kpoct@kp.org
Aarati V. Rao
- Recruiting
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, 73104
Site Public Contact, 405-271-8777, ou-clinical-trials@ouhsc.edu
Rene Y. McNall-Knapp
- Recruiting
Children's Hospital and Medical Center of Omaha
Omaha, Nebraska, 68114
Site Public Contact, 402-955-3949
Jill C. Beck
- Recruiting
University of Nebraska Medical Center
Omaha, Nebraska, 68198
Site Public Contact, 402-559-6941, unmcrsa@unmc.edu
Jill C. Beck
- Recruiting
Arnold Palmer Hospital for Children
Orlando, Florida, 32806
Site Public Contact, 321-841-5357, Jennifer.spinelli@orlandohealth.com
Jaime M. Libes-Bander
- Recruiting
Nemours Children's Hospital
Orlando, Florida, 32827
Site Public Contact, 302-651-5572, Allison.bruce@nemours.org
Sridhi Patel
- Recruiting
Saint Joseph's Regional Medical Center
Paterson, New Jersey, 07503
Site Public Contact, 973-754-2207, HallL@sjhmc.org
Alissa Kahn
- Recruiting
Nemours Children's Clinic - Pensacola
Pensacola, Florida, 32504
Site Public Contact, helpdesk@childrensoncologygroup.org
Jeffrey H. Schwartz
- Recruiting
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
Site Public Contact, 267-425-5544, CancerTrials@email.chop.edu
Frank M. Balis
- Recruiting
Phoenix Childrens Hospital
Phoenix, Arizona, 85016
Site Public Contact, 602-546-0920
Alok K. Kothari
- Recruiting
Children's Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania, 15224
Site Public Contact, 412-692-8570, jean.tersak@chp.edu
Brittani K. Seynnaeve
- Not yet recruiting
Oregon Health and Science University
Portland, Oregon, 97239
Site Public Contact, 503-494-1080, trials@ohsu.edu
Katrina Winsnes
- Recruiting
Mayo Clinic in Rochester
Rochester, Minnesota, 55905
Site Public Contact, 855-776-0015
Peter Schoettler
- Recruiting
Primary Children's Hospital
Salt Lake City, Utah, 84113
Site Public Contact, 801-585-5270
Matthew Dietz
- Recruiting
Children's Hospital of San Antonio
San Antonio, Texas, 78207
Site Public Contact, 210-704-2894, bridget.medina@christushealth.org
Julie Voeller
- Recruiting
Methodist Children's Hospital of South Texas
San Antonio, Texas, 78229
Site Public Contact, 210-575-6240, Vinod.GidvaniDiaz@hcahealthcare.com
Jose M. Esquilin
- Recruiting
UCSF Medical Center-Mission Bay
San Francisco, California, 94158
Site Public Contact, 877-827-3222, cancertrials@ucsf.edu
Arun A. Rangaswami
- Not yet recruiting
Seattle Children's Hospital
Seattle, Washington, 98105
Site Public Contact, 866-987-2000
Sarah E. Leary
- Recruiting
Sanford USD Medical Center - Sioux Falls
Sioux Falls, South Dakota, 57117-5134
Site Public Contact, 605-312-3320, OncologyClinicalTrialsSF@SanfordHealth.org
Kayelyn J. Wagner
- Recruiting
Providence Sacred Heart Medical Center and Children's Hospital
Spokane, Washington, 99204
Site Public Contact, 800-228-6618, HopeBeginsHere@providence.org
Judy L. Felgenhauer
- Recruiting
Washington University School of Medicine
St Louis, Missouri, 63110
Site Public Contact, 800-600-3606, info@siteman.wustl.edu
Frederick S. Huang
- Recruiting
Johns Hopkins All Children's Hospital
St. Petersburg, Florida, 33701
Site Public Contact, 727-767-4784, Ashley.Repp@jhmi.edu
Blake Foxworthy
- Recruiting
Saint Joseph's Hospital/Children's Hospital-Tampa
Tampa, Florida, 33607
Site Public Contact, 813-357-0849, jennifer.manns@baycare.org
Don E. Eslin
- Recruiting
Montefiore Medical Center - Moses Campus
The Bronx, New York, 10467
Site Public Contact, 718-379-6866, eskwak@montefiore.org
Alice Lee
- Recruiting
ProMedica Toledo Hospital/Russell J Ebeid Children's Hospital
Toledo, Ohio, 43606
Site Public Contact, 419-824-1842, PCIOncResearch@promedica.org
Jamie L. Dargart
- Recruiting
Saint Francis Children's Hospital
Tulsa, Oklahoma, 74136
Site Public Contact, 918-502-6720
Jill A. Salo
- Recruiting
New York Medical College
Valhalla, New York, 10595
Site Public Contact, 914-594-3794
Andrew J. Bellantoni
- Recruiting
Children's National Medical Center
Washington D.C., District of Columbia, 20010
Site Public Contact, 202-476-2800, OncCRC_OnCall@childrensnational.org
Jeffrey S. Dome
- Recruiting
Alfred I duPont Hospital for Children
Wilmington, Delaware, 19803
Site Public Contact, 302-651-5572, Allison.bruce@nemours.org
Sridhi Patel
Canada7 sites, 7 recruiting
- Recruiting
IWK Health Centre
Halifax, Nova Scotia, B3K 6R8
Site Public Contact, 902-470-8520, Research@iwk.nshealth.ca
Chelsea Ash
- Recruiting
The Montreal Children's Hospital of the MUHC
Montreal, Quebec, H3H 1P3
Site Public Contact, 514-412-4445, info@thechildren.com
Stephanie Mourad
- Recruiting
Centre Hospitalier Universitaire Sainte-Justine
Montreal, Quebec, H3T 1C5
Site Public Contact, 514-345-4931, yvan.samson@umontreal.ca
Monia Marzouki
- Recruiting
CHU de Quebec-Centre Hospitalier de l'Universite Laval (CHUL)
Québec, G1V 4G2
Site Public Contact, 418-525-4444, rechclinique@crchudequebec.ulaval.ca
Bruno Michon
- Recruiting
Centre Hospitalier Universitaire de Sherbrooke-Fleurimont
Sherbrooke, Quebec, J1H 5N4
Site Public Contact, 819-820-6480, crcinformation.chus@ssss.gouv.qc.ca
Josee Brossard
- Recruiting
Hospital for Sick Children
Toronto, Ontario, M5G 1X8
Site Public Contact, 416-813-7654, ask.CRS@sickkids.ca
David Malkin
- Recruiting
CancerCare Manitoba
Winnipeg, Manitoba, R3E 0V9
Site Public Contact, 866-561-1026, ctu_web@cancercare.mb.ca
Stephanie M. Villeneuve
About this study
Official title: Prospective Treatment of Types I, II and III Pleuropulmonary Blastoma (PPB)
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.
Read the detailed description
PRIMARY OBJECTIVE:
- To determine the overall response rate (complete response [CR] + partial response [PR]) to 2 cycles of window therapy with vincristine, topotecan and cyclophosphamide in children with Types II and III pleuropulmonary blastoma (PPB) using Response Evaluation Criteria in Solid Tumors (RECIST) criteria.
SECONDARY OBJECTIVES:
- To estimate 3-year progression-free survival (PFS) and overall survival (OS) in children with Types II and III PPB.
II. To estimate 3-year PFS and OS in children with Type I PPB treated with surgery or surgery and chemotherapy using standardized guidelines.
EXPLORATORY OBJECTIVES:
- To assess primary resection rate in children with Types I, II and III PPB using central radiology review and standardized surgical guidelines.
II. To assess surgical complications among those undergoing primary resection versus (vs.) biopsy followed by neoadjuvant chemotherapy for Types II and III PPB.
III. To establish a new cohort of prospectively treated children with newly diagnosed PPB which will serve as a comparison group for future novel agent trials.
IV. To evaluate toxicities in children treated for PPB including late cardiopulmonary toxicity.
- To evaluate the molecular genetics/epigenetics of PPB and correlate with outcomes.
VI. To collect tumor tissue and serial blood samples for tumor profiling, liquid biopsies, and future correlative biology studies.
OUTLINE: Patients are assigned to 1 of 2 groups. For both groups, tumor tissue is centrally reviewed by a study pathologist. Blood samples are collected at specific clinical timepoints.
GROUP I (TYPE I/Ir PPB): Patients < 5 years old with Type I PPB whose tumor was not able to be completely removed by surgery are assigned to Arm 1. All other patients are assigned to Arm 2.
ARM 1 (VAC1200/VA REGIMEN): Patients receive vincristine intravenously (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. Patients also undergo blood sample collection, computed tomography (CT) and ultrasound throughout the study.
ARM 2: Patients undergo observation on study. This includes blood sample collection, chest CT, and ultrasound throughout the study.
GROUP II: (TYPE II/III PPB):
CYCLES 1-2 (VTC400 REGIMEN): Patients receive vincristine IV on days 1, 8, and 15 of each cycle, topotecan IV over 30 minutes on days 1-5 of each cycle, and cyclophosphamide IV over 15-30 minutes on days 1-5 of each cycle. Cycles repeat every 21 days for 2 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo multi-gated acquisition (MUGA) or echocardiography (ECHO), positron emission tomography (PET) or bone scan, CT, magnetic resonance imaging (MRI), and blood sample collection throughout the study.
Patients with complete response, partial response, or stable disease after cycle 2 are assigned to Arm 3. Patients with disease progression after cycle 2 are assigned to Arm 4. Patients also undergo surgery and radiation therapy as clinically indicated.
ARM 3:
CYCLES 3-6 (IVADo REGIMEN): Patients receive vincristine IV on day 1 of each cycle, dactinomycin IV over 1-5 or 10-15 minutes on day 1 of each cycle, ifosfamide IV over 3 hours on days 1-2 of each cycle, dexrazoxane IV over 5-15 minutes on days 1-2 of each cycle, and doxorubicin IV over 3-15 minutes on days 1-2 of each cycle. Cycles repeat every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity.
CYCLES 7, 9, 11 (VTC250 REGIMEN): Patients receive vincristine IV on days 1, 8, and 15 of each cycle, topotecan IV over 30 minutes on days 1-5 of each cycle, and cyclophosphamide IV over 15-30 minutes on days 1-5 of each cycle. Treatment continues for 21 days every odd cycle for 3 cycles in the absence of disease progression or unacceptable toxicity.
CYCLES 8, 10, 12 (VAC1200 REGIMEN): Patients receive vincristine IV on day 1 of each cycle, 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 each cycle. Treatment continues for 21 days every even cycle for 3 cycles in the absence of disease progression or unacceptable toxicity.
ARM 4:
CYCLES 3-6 (IVADo REGIMEN): Patients receive vincristine IV on day 1 of each cycle, dactinomycin IV over 1-5 or 10-15 minutes on day 1 of each cycle, ifosfamide IV over 3 hours on days 1-2 of each cycle, dexrazoxane IV over 5-15 minutes on days 1-2 of each cycle, and doxorubicin IV over 3-15 minutes on days 1-2 of each cycle. Cycles repeat every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity.
CYCLES 7-12 (IVA REGIMEN): Patients receive vincristine IV on day 1 of each cycle, dactinomycin IV over 1-5 or 10-15 minutes on day 1 of each cycle, and ifosfamide IV over 3 hours on day 1 of each cycle. Cycles repeat every 21 days for 6 cycles in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed every 3 months for 24 months, then every 6 months until 5 years.
- Conditions
- Pleuropulmonary Blastoma
- Being tested
- Biospecimen Collection, Bone Scan, Computed Tomography, Cyclophosphamide, Dactinomycin
- Medical subject headings
- Pleuropulmonary blastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Biospecimen CollectionProcedure or surgery
Also called Biological Sample Collection, Biospecimen Collected, Specimen Collection
Undergo collection of blood samples
Biospecimen CollectionProcedure or surgery
Also called Biological Sample Collection, Biospecimen Collected, Specimen Collection
Tumor tissue is collected and centrally reviewed by a study pathologist
Bone ScanProcedure or surgery
Also called Bone Scintigraphy
Undergo bone scan
Computed TomographyProcedure or surgery
Also called CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography
Undergo CT
CyclophosphamideDrug
Also called (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Asta B 518, B 518
Given IV
DactinomycinBiological
Also called Actinomycin A IV, Actinomycin C1, Actinomycin D, Actinomycin I1
Given IV
DexrazoxaneDrug
Also called 2, 6-Piperazinedione, 4,4'-propylenedi-, (P)- (8CI), 2,6-Piperazinedione, 4, 4'-(1-methyl-1,2-ethanediyl)bis-, (S)- (9CI), ADR 529, ADR-529
Given IV
DoxorubicinDrug
Also called Adriablastin, Hydroxydaunomycin, Hydroxyl Daunorubicin, Hydroxyldaunorubicin
Given IV
Echocardiography TestProcedure or surgery
Also called EC, Echocardiography
Undergo ECHO
IfosfamideDrug
Also called Asta Z 4942, Asta Z-4942, Cyfos, Holoxan
Given IV
Magnetic Resonance ImagingProcedure or surgery
Also called Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan
Undergo MRI
Multigated Acquisition ScanProcedure or surgery
Also called Blood Pool Scan, Equilibrium Radionuclide Angiography, Gated Blood Pool Imaging, Gated Heart Pool Scan
Undergo MUGA
Patient ObservationOther
Also called Active Surveillance, deferred therapy, expectant management, Observation
Undergo observation
Positron Emission TomographyProcedure or surgery
Also called Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron emission tomography (procedure)
Undergo PET
TopotecanDrug
Also called Hycamptamine, Topotecan Lactone
Given IV
Ultrasound ImagingProcedure or surgery
Also called 2-Dimensional Grayscale Ultrasound Imaging, 2-Dimensional Ultrasound Imaging, 2D-US, Ultrasonography
Undergo ultrasound
VincristineDrug
Also called LCR, Leurocristine, VCR, Vincrystine
Given IV
| Study group | Role | What they receive |
|---|---|---|
| Group I, Arm 1 (VAC1200/VA regimen) | Experimental | 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. Receives: Procedure: Biospecimen Collection; Procedure: Computed Tomography; Drug: Cyclophosphamide; Biological: Dactinomycin; Procedure: Ultrasound Imaging; Drug: Vincristine |
| Group I, Arm 2 (observation) | Active comparator | 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. Receives: Procedure: Biospecimen Collection; Procedure: Computed Tomography; Other: Patient Observation; Procedure: Ultrasound Imaging |
| Group II, Arm 3 (VTC400, IVADo, VTC250, VAC1200 regimens) | Experimental | See Detailed Description for Group II, Arm 3. Receives: Procedure: Biospecimen Collection; Procedure: Bone Scan; Procedure: Computed Tomography; Drug: Cyclophosphamide; Biological: Dactinomycin; Drug: Dexrazoxane; Drug: Doxorubicin; Procedure: Echocardiography Test; Drug: Ifosfamide; Procedure: Magnetic Resonance Imaging; Procedure: Multigated Acquisition Scan; Procedure: Positron Emission Tomography; Drug: Topotecan; Drug: Vincristine |
| Group II, Arm 4 (VTC400, IVADo, IVA regimens) | Experimental | See Detailed Description for Group II, Arm 4. Receives: Procedure: Biospecimen Collection; Procedure: Bone Scan; Procedure: Computed Tomography; Drug: Cyclophosphamide; Biological: Dactinomycin; Drug: Dexrazoxane; Drug: Doxorubicin; Procedure: Echocardiography Test; Drug: Ifosfamide; Procedure: Magnetic Resonance Imaging; Procedure: Multigated Acquisition Scan; Procedure: Positron Emission Tomography; Drug: Topotecan; Drug: Vincristine |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Up to 2 cycles (cycles = 21 days) of window therapy with vincristine, topotecan and cyclophosphamide
Secondary outcomes (4)
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.
Measured: From date of enrollment to the earliest occurrence of relapse, disease progression, or death due to any cause, assessed up to 3 years
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.
Measured: From date of enrollment to date of death due to any reason, assessed up to 3 years
PFS in children with Types I PPB
3-year PFS, along with the confidence intervals will be estimated using the Kaplan-Meier method.
Measured: From date of enrollment to the earliest occurrence of relapse, disease progression, or death due to any cause, assessed up to 3 years
OS in children with Types I PPB
3-year OS, along with the confidence intervals will be estimated using the Kaplan-Meier method.
Measured: From date of enrollment to date of death due to any reason, assessed up to 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Oct 2024
- Study start21 Mar 2025
- Primary completion31 Mar 2029 (estimated)
- Study completion31 Mar 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Pleuropulmonary BlastomaStudies of the same condition, open and under way.
- More trials run by Children's Oncology GroupThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 110 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Children's Oncology Group
- Sponsor type
- Research network
- Responsible party
- Sponsor
- Investigators
- Kris Ann P Schultz, Principal investigator, Children's Oncology Group
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06647953
- Sponsor's protocol ID
- ARAR2331
- Other IDs
- NCI-2024-08232, ARAR2331, ARAR2331, U10CA180886
- Status last verified
- Mar 2026
- First submitted
- 10 Oct 2024
- Last updated
- 25 Aug 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No