Recruiting
Phase 3

Surgery & Chemotherapy

Sponsor:

Children's Oncology Group

Code:

NCT06647953

Conditions

Pleuropulmonary Blastoma

Eligibility Criteria

Sex: All

Age: 0 - 21

Healthy Volunteers: Not accepted

Interventions

Biospecimen Collection

Biospecimen Collection

Bone Scan

Computed Tomography

Cyclophosphamide

Study Details

Brief 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 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.

Conditions

Pleuropulmonary Blastoma

Study ID

NCT06647953

Start date

Mar 21, 2025

Status verified date

Mar, 2026

Completion date

Mar 31, 2029

Anticipated

Primary completion date

Mar 31, 2029

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 0 - 21

Healthy Volunteers: Not accepted

Inclusion Criteria:

  • 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)
  • 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

Exclusion Criteria:

  • 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

Study Design

Enrollment

110 participants

Anticipated

Allocation

Non randomized

Intervention Model

Sequential

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Group I, Arm 1 (VAC1200/VA regimen)

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.

active comparator: Group I, Arm 2 (observation)

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.

experimental: Group II, Arm 3 (VTC400, IVADo, VTC250, VAC1200 regimens)

See Detailed Description for Group II, Arm 3.

experimental: Group II, Arm 4 (VTC400, IVADo, IVA regimens)

See Detailed Description for Group II, Arm 4.

Interventions

Biospecimen Collection

Undergo collection of blood samples

Biospecimen Collection

Tumor tissue is collected and centrally reviewed by a study pathologist

Bone Scan

Undergo bone scan

Computed Tomography

Undergo CT

Cyclophosphamide

Given IV

Dactinomycin

Given IV

Dexrazoxane

Given IV

Doxorubicin

Given IV

Echocardiography Test

Undergo ECHO

Ifosfamide

Given IV

Magnetic Resonance Imaging

Undergo MRI

Multigated Acquisition Scan

Undergo MUGA

Patient Observation

Undergo observation

Positron Emission Tomography

Undergo PET

Topotecan

Given IV

Ultrasound Imaging

Undergo ultrasound

Vincristine

Given IV

Primary outcome measure

  • Objective response [ Time Frame: Up to 2 cycles (cycles = 21 days) of window therapy with vincristine, topotecan and cyclophosphamide ]

Central Contacts and Locations

Locations

Children's Hospital of Alabama

Recruiting

Birmingham, Alabama, United States, 35233

Contacts

Principal Investigator:

Elizabeth D. Alva

Phoenix Childrens Hospital

Recruiting

Phoenix, Arizona, United States, 85016

Contacts

Site Public Contact

602-546-0920

Principal Investigator:

Alok K. Kothari

Arkansas Children's Hospital

Recruiting

Little Rock, Arkansas, United States, 72202-3591

Contacts

Site Public Contact

501-364-7373

Principal Investigator:

Michael W. Bishop

Kaiser Permanente Downey Medical Center

Recruiting

Downey, California, United States, 90242

Contacts

Site Public Contact

626-564-3455

Principal Investigator:

Robert M. Cooper

Loma Linda University Medical Center

Recruiting

Loma Linda, California, United States, 92354

Contacts

Site Public Contact

909-558-4050

Principal Investigator:

Albert Kheradpour

Children's Hospital Los Angeles

Recruiting

Los Angeles, California, United States, 90027

Contacts

Site Public Contact

323-361-4110

Principal Investigator:

Rachana Shah

Valley Children's Hospital

Recruiting

Madera, California, United States, 93636

Contacts

Principal Investigator:

Ruetima Titapiwatanakun

UCSF Benioff Children's Hospital Oakland

Recruiting

Oakland, California, United States, 94609

Contacts

Principal Investigator:

Arun A. Rangaswami

Kaiser Permanente-Oakland

Recruiting

Oakland, California, United States, 94611

Contacts

Site Public Contact

877-642-4691Kpoct@kp.org

Principal Investigator:

Aarati V. Rao

UCSF Medical Center-Mission Bay

Recruiting

San Francisco, California, United States, 94158

Contacts

Principal Investigator:

Arun A. Rangaswami

Children's Hospital Colorado

Recruiting

Aurora, Colorado, United States, 80045

Contacts

Principal Investigator:

Navin R. Pinto

Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center

Recruiting

Denver, Colorado, United States, 80218

Contacts

Principal Investigator:

Florence Choo

Alfred I duPont Hospital for Children

Recruiting

Wilmington, Delaware, United States, 19803

Contacts

Principal Investigator:

Sridhi Patel

Children's National Medical Center

Recruiting

Washington D.C., District of Columbia, United States, 20010

Contacts

Principal Investigator:

Jeffrey S. Dome

Golisano Children's Hospital of Southwest Florida

Recruiting

Fort Myers, Florida, United States, 33908

Contacts

Principal Investigator:

Emad K. Salman

Nemours Children's Clinic-Jacksonville

Recruiting

Jacksonville, Florida, United States, 32207

Contacts

Principal Investigator:

Sridhi Patel

Nicklaus Children's Hospital

Recruiting

Miami, Florida, United States, 33155

Contacts

Site Public Contact

888-624-2778

Principal Investigator:

Maggie E. Fader

Arnold Palmer Hospital for Children

Recruiting

Orlando, Florida, United States, 32806

Contacts

Principal Investigator:

Jaime M. Libes-Bander

Nemours Children's Hospital

Recruiting

Orlando, Florida, United States, 32827

Contacts

Principal Investigator:

Sridhi Patel

Nemours Children's Clinic - Pensacola

Recruiting

Pensacola, Florida, United States, 32504

Contacts

Principal Investigator:

Jeffrey H. Schwartz

Johns Hopkins All Children's Hospital

Recruiting

St. Petersburg, Florida, United States, 33701

Contacts

Principal Investigator:

Blake Foxworthy

Saint Joseph's Hospital/Children's Hospital-Tampa

Recruiting

Tampa, Florida, United States, 33607

Contacts

Principal Investigator:

Don E. Eslin

Children's Healthcare of Atlanta - Arthur M Blank Hospital

Recruiting

Atlanta, Georgia, United States, 30329

Contacts

Principal Investigator:

Sarah G. Mitchell

Lurie Children's Hospital-Chicago

Recruiting

Chicago, Illinois, United States, 60611

Contacts

Site Public Contact

773-880-4562

Principal Investigator:

Elizabeth A. Sokol

University of Chicago Comprehensive Cancer Center

Recruiting

Chicago, Illinois, United States, 60637

Contacts

Principal Investigator:

Lorraine E. Canham

Riley Hospital for Children

Recruiting

Indianapolis, Indiana, United States, 46202

Contacts

Site Public Contact

800-248-1199

Principal Investigator:

Marissa Just

University of Iowa/Holden Comprehensive Cancer Center

Recruiting

Iowa City, Iowa, United States, 52242

Contacts

Site Public Contact

800-237-1225

Principal Investigator:

Andrew P. Groves

Norton Children's Hospital

Recruiting

Louisville, Kentucky, United States, 40202

Contacts

Principal Investigator:

Michael J. Ferguson

Children's Hospital New Orleans

Recruiting

New Orleans, Louisiana, United States, 70118

Contacts

Site Public Contact

504-894-5377

Principal Investigator:

Maria C. Velez-Yanguas

Johns Hopkins University/Sidney Kimmel Cancer Center

Recruiting

Baltimore, Maryland, United States, 21287

Contacts

Principal Investigator:

Lindy Zhang

Dana-Farber Cancer Institute

Recruiting

Boston, Massachusetts, United States, 02215

Contacts

Site Public Contact

877-442-3324

Principal Investigator:

Junne Kamihara

C S Mott Children's Hospital

Recruiting

Ann Arbor, Michigan, United States, 48109

Contacts

Site Public Contact

800-865-1125

Principal Investigator:

Rama Jasty

Children's Hospital of Michigan

Recruiting

Detroit, Michigan, United States, 48201

Contacts

Principal Investigator:

Alissa M. Martin

Corewell Health Grand Rapids Hospitals - Helen DeVos Children's Hospital

Recruiting

Grand Rapids, Michigan, United States, 49503

Contacts

Principal Investigator:

Kathleen Y. Butler

Bronson Methodist Hospital

Recruiting

Kalamazoo, Michigan, United States, 49007

Contacts

Principal Investigator:

Kathleen Y. Butler

Children's Hospitals and Clinics of Minnesota - Minneapolis

Recruiting

Minneapolis, Minnesota, United States, 55404

Contacts

Principal Investigator:

Michael K. Richards

Mayo Clinic in Rochester

Recruiting

Rochester, Minnesota, United States, 55905

Contacts

Site Public Contact

855-776-0015

Principal Investigator:

Peter Schoettler

University of Mississippi Medical Center

Recruiting

Jackson, Mississippi, United States, 39216

Contacts

Site Public Contact

601-815-6700

Principal Investigator:

Amanda Strobel

Children's Mercy Hospitals and Clinics

Recruiting

Kansas City, Missouri, United States, 64108

Contacts

Principal Investigator:

Keith J. August

Washington University School of Medicine

Recruiting

St Louis, Missouri, United States, 63110

Contacts

Principal Investigator:

Frederick S. Huang

Children's Hospital and Medical Center of Omaha

Recruiting

Omaha, Nebraska, United States, 68114

Contacts

Site Public Contact

402-955-3949

Principal Investigator:

Jill C. Beck

University of Nebraska Medical Center

Recruiting

Omaha, Nebraska, United States, 68198

Contacts

Principal Investigator:

Jill C. Beck

Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital

Recruiting

New Brunswick, New Jersey, United States, 08903

Contacts

Site Public Contact

732-235-8675

Principal Investigator:

Scott Moerdler

Saint Joseph's Regional Medical Center

Recruiting

Paterson, New Jersey, United States, 07503

Contacts

Site Public Contact

973-754-2207HallL@sjhmc.org

Principal Investigator:

Alissa Kahn

Albany Medical Center

Recruiting

Albany, New York, United States, 12208

Contacts

Site Public Contact

518-262-5513

Principal Investigator:

Lauren R. Weintraub

The Steven and Alexandra Cohen Children's Medical Center of New York

Recruiting

New Hyde Park, New York, United States, 11040

Contacts

Site Public Contact

718-470-3460

Principal Investigator:

Carolyn F. Levy

Montefiore Medical Center - Moses Campus

Recruiting

The Bronx, New York, United States, 10467

Contacts

Principal Investigator:

Alice Lee

New York Medical College

Recruiting

Valhalla, New York, United States, 10595

Contacts

Site Public Contact

914-594-3794

Principal Investigator:

Andrew J. Bellantoni

UNC Lineberger Comprehensive Cancer Center

Recruiting

Chapel Hill, North Carolina, United States, 27599

Contacts

Principal Investigator:

Thomas B. Alexander

Duke University Medical Center

Recruiting

Durham, North Carolina, United States, 27710

Contacts

Site Public Contact

888-275-3853

Principal Investigator:

Jessica M. Sun

Sanford Broadway Medical Center

Recruiting

Fargo, North Dakota, United States, 58122

Contacts

Principal Investigator:

Samuel J. Milanovich

Cincinnati Children's Hospital Medical Center

Recruiting

Cincinnati, Ohio, United States, 45229

Contacts

Principal Investigator:

Brian K. Turpin

Rainbow Babies and Childrens Hospital

Recruiting

Cleveland, Ohio, United States, 44106

Contacts

Site Public Contact

216-844-5437

Principal Investigator:

Duncan S. Stearns

Nationwide Children's Hospital

Recruiting

Columbus, Ohio, United States, 43205

Contacts

Principal Investigator:

Mark A. Ranalli

Dayton Children's Hospital

Recruiting

Dayton, Ohio, United States, 45404

Contacts

Site Public Contact

800-228-4055

Principal Investigator:

Jordan M. Wright

ProMedica Toledo Hospital/Russell J Ebeid Children's Hospital

Recruiting

Toledo, Ohio, United States, 43606

Contacts

Principal Investigator:

Jamie L. Dargart

University of Oklahoma Health Sciences Center

Recruiting

Oklahoma City, Oklahoma, United States, 73104

Contacts

Principal Investigator:

Rene Y. McNall-Knapp

Saint Francis Children's Hospital

Recruiting

Tulsa, Oklahoma, United States, 74136

Contacts

Site Public Contact

918-502-6720

Principal Investigator:

Jill A. Salo

Children's Hospital of Philadelphia

Recruiting

Philadelphia, Pennsylvania, United States, 19104

Contacts

Principal Investigator:

Frank M. Balis

Children's Hospital of Pittsburgh of UPMC

Recruiting

Pittsburgh, Pennsylvania, United States, 15224

Contacts

Principal Investigator:

Brittani K. Seynnaeve

BI-LO Charities Children's Cancer Center

Recruiting

Greenville, South Carolina, United States, 29605

Contacts

Principal Investigator:

Aniket Saha

Sanford USD Medical Center - Sioux Falls

Recruiting

Sioux Falls, South Dakota, United States, 57117-5134

Contacts

Principal Investigator:

Kayelyn J. Wagner

Saint Jude Children's Research Hospital

Recruiting

Memphis, Tennessee, United States, 38105

Contacts

Principal Investigator:

Alberto S. Pappo

The Children's Hospital at TriStar Centennial

Recruiting

Nashville, Tennessee, United States, 37203

Contacts

Site Public Contact

615-342-1919

Principal Investigator:

Clinton M. Carroll

Vanderbilt University/Ingram Cancer Center

Recruiting

Nashville, Tennessee, United States, 37232

Contacts

Site Public Contact

800-811-8480

Principal Investigator:

Daniel J. Benedetti

Dell Children's Medical Center of Central Texas

Recruiting

Austin, Texas, United States, 78723

Contacts

Principal Investigator:

Shannon M. Cohn

UT Southwestern/Simmons Cancer Center-Dallas

Recruiting

Dallas, Texas, United States, 75390

Contacts

Principal Investigator:

Avanthi T. Shah

Cook Children's Medical Center

Recruiting

Fort Worth, Texas, United States, 76104

Contacts

Principal Investigator:

Kelly L. Vallance

Covenant Children's Hospital

Recruiting

Lubbock, Texas, United States, 79410

Contacts

Principal Investigator:

Kishor M. Bhende

Children's Hospital of San Antonio

Recruiting

San Antonio, Texas, United States, 78207

Contacts

Principal Investigator:

Julie Voeller

Methodist Children's Hospital of South Texas

Recruiting

San Antonio, Texas, United States, 78229

Contacts

Principal Investigator:

Jose M. Esquilin

Primary Children's Hospital

Recruiting

Salt Lake City, Utah, United States, 84113

Contacts

Site Public Contact

801-585-5270

Principal Investigator:

Matthew Dietz

University of Virginia Cancer Center

Recruiting

Charlottesville, Virginia, United States, 22908

Contacts

Principal Investigator:

Brian C. Belyea

Children's Hospital of The King's Daughters

Recruiting

Norfolk, Virginia, United States, 23507

Contacts

Principal Investigator:

Melissa S. Mark

Providence Sacred Heart Medical Center and Children's Hospital

Recruiting

Spokane, Washington, United States, 99204

Contacts

Principal Investigator:

Judy L. Felgenhauer

Saint Vincent Hospital Cancer Center Green Bay

Recruiting

Green Bay, Wisconsin, United States, 54301

Contacts

Principal Investigator:

Catherine A. Long

University of Wisconsin Carbone Cancer Center - University Hospital

Recruiting

Madison, Wisconsin, United States, 53792

Contacts

Principal Investigator:

Margo L. Hoover-Regan

CancerCare Manitoba

Recruiting

Winnipeg, Manitoba, Canada, R3E 0V9

Contacts

Principal Investigator:

Stephanie M. Villeneuve

IWK Health Centre

Recruiting

Halifax, Nova Scotia, Canada, B3K 6R8

Contacts

Principal Investigator:

Chelsea Ash

Hospital for Sick Children

Recruiting

Toronto, Ontario, Canada, M5G 1X8

Contacts

Principal Investigator:

David Malkin

The Montreal Children's Hospital of the MUHC

Recruiting

Montreal, Quebec, Canada, H3H 1P3

Contacts

Principal Investigator:

Stephanie Mourad

Centre Hospitalier Universitaire Sainte-Justine

Recruiting

Montreal, Quebec, Canada, H3T 1C5

Contacts

Principal Investigator:

Monia Marzouki

Centre Hospitalier Universitaire de Sherbrooke-Fleurimont

Recruiting

Sherbrooke, Quebec, Canada, J1H 5N4

Contacts

Principal Investigator:

Josee Brossard

CHU de Quebec-Centre Hospitalier de l'Universite Laval (CHUL)

Recruiting

Québec, Canada, G1V 4G2

Contacts

Principal Investigator:

Bruno Michon

More Information

Sponsor

Children's Oncology Group

Last update posted

Aug 25, 2026

Last verified

Mar, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-10-08. This information was provided to ClinicalTrials.gov by Children's Oncology Group on 2026-08-25. Recruitment status is synced daily from ClinicalTrials.gov and may not reflect the sponsor's current status. Confirm during your call.