Trial Title:
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
NCT ID:
NCT06647953
Condition:
Pleuropulmonary Blastoma
Conditions: Official terms:
Pulmonary Blastoma
Dactinomycin
Cyclophosphamide
Ifosfamide
Isophosphamide mustard
Doxorubicin
Liposomal doxorubicin
Vincristine
Daunorubicin
Topotecan
Dexrazoxane
Razoxane
3,6-bis(5-chloro-2-piperidyl)-2,5-piperazinedione
Study type:
Interventional
Study phase:
Phase 3
Overall status:
Not yet recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Sequential Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Procedure
Intervention name:
Biospecimen Collection
Description:
Undergo collection of blood samples
Arm group label:
Group I, Arm 1 (VAC1200/VA regimen)
Arm group label:
Group II, Arm 3 (VTC400, IVADo, VTC250, VAC1200 regimens)
Arm group label:
Group II, Arm 4 (VTC400, IVADo, IVA regimens)
Other name:
Biological Sample Collection
Other name:
Biospecimen Collected
Other name:
Specimen Collection
Intervention type:
Procedure
Intervention name:
Bone Scan
Description:
Undergo bone scan
Arm group label:
Group II, Arm 3 (VTC400, IVADo, VTC250, VAC1200 regimens)
Arm group label:
Group II, Arm 4 (VTC400, IVADo, IVA regimens)
Other name:
Bone Scintigraphy
Intervention type:
Procedure
Intervention name:
Computed Tomography
Description:
Undergo CT
Arm group label:
Group I, Arm 1 (VAC1200/VA regimen)
Arm group label:
Group II, Arm 3 (VTC400, IVADo, VTC250, VAC1200 regimens)
Arm group label:
Group II, Arm 4 (VTC400, IVADo, IVA regimens)
Other name:
CAT
Other name:
CAT Scan
Other name:
Computed Axial Tomography
Other name:
Computerized Axial Tomography
Other name:
Computerized axial tomography (procedure)
Other name:
Computerized Tomography
Other name:
Computerized Tomography (CT) scan
Other name:
CT
Other name:
CT Scan
Other name:
tomography
Intervention type:
Drug
Intervention name:
Cyclophosphamide
Description:
Given IV
Arm group label:
Group I, Arm 1 (VAC1200/VA regimen)
Arm group label:
Group II, Arm 3 (VTC400, IVADo, VTC250, VAC1200 regimens)
Arm group label:
Group II, Arm 4 (VTC400, IVADo, IVA regimens)
Other name:
(-)-Cyclophosphamide
Other name:
2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate
Other name:
Asta B 518
Other name:
B 518
Other name:
B-518
Other name:
B518
Other name:
Carloxan
Other name:
Ciclofosfamida
Other name:
Ciclofosfamide
Other name:
Cicloxal
Other name:
Clafen
Other name:
Claphene
Other name:
CP monohydrate
Other name:
CTX
Other name:
CYCLO-cell
Other name:
Cycloblastin
Other name:
Cycloblastine
Other name:
Cyclophospham
Other name:
Cyclophosphamid monohydrate
Other name:
Cyclophosphamide Monohydrate
Other name:
Cyclophosphamidum
Other name:
Cyclophosphan
Other name:
Cyclophosphane
Other name:
Cyclophosphanum
Other name:
Cyclostin
Other name:
Cyclostine
Other name:
Cytophosphan
Other name:
Cytophosphane
Other name:
Cytoxan
Other name:
Fosfaseron
Other name:
Genoxal
Other name:
Genuxal
Other name:
Ledoxina
Other name:
Mitoxan
Other name:
Neosar
Other name:
Revimmune
Other name:
Syklofosfamid
Other name:
WR 138719
Other name:
WR- 138719
Other name:
WR-138719
Other name:
WR138719
Intervention type:
Biological
Intervention name:
Dactinomycin
Description:
Given IV
Arm group label:
Group I, Arm 1 (VAC1200/VA regimen)
Arm group label:
Group II, Arm 3 (VTC400, IVADo, VTC250, VAC1200 regimens)
Arm group label:
Group II, Arm 4 (VTC400, IVADo, IVA regimens)
Other name:
Actinomycin A IV
Other name:
Actinomycin C1
Other name:
Actinomycin D
Other name:
Actinomycin I1
Other name:
Actinomycin IV
Other name:
Actinomycin X 1
Other name:
Actinomycin-[thr-val-pro-sar-meval]
Other name:
Cosmegen
Other name:
DACT
Other name:
Dactinomycine
Other name:
Lyovac Cosmegen
Other name:
Meractinomycin
Intervention type:
Drug
Intervention name:
Dexrazoxane
Description:
Given IV
Arm group label:
Group II, Arm 3 (VTC400, IVADo, VTC250, VAC1200 regimens)
Arm group label:
Group II, Arm 4 (VTC400, IVADo, IVA regimens)
Other name:
2, 6-Piperazinedione, 4,4'-propylenedi-, (P)- (8CI)
Other name:
2,6-Piperazinedione, 4, 4'-(1-methyl-1,2-ethanediyl)bis-, (S)- (9CI)
Other name:
ADR 529
Other name:
ADR-529
Other name:
ADR529
Other name:
ICRF 187
Other name:
ICRF-187
Other name:
ICRF187
Other name:
Razoxane (+)-form
Other name:
Soluble ICRF (L-isomer)
Intervention type:
Drug
Intervention name:
Doxorubicin
Description:
Given IV
Arm group label:
Group II, Arm 3 (VTC400, IVADo, VTC250, VAC1200 regimens)
Arm group label:
Group II, Arm 4 (VTC400, IVADo, IVA regimens)
Other name:
Adriablastin
Other name:
Hydroxydaunomycin
Other name:
Hydroxyl Daunorubicin
Other name:
Hydroxyldaunorubicin
Intervention type:
Procedure
Intervention name:
Echocardiography
Description:
Undergo ECHO
Arm group label:
Group II, Arm 3 (VTC400, IVADo, VTC250, VAC1200 regimens)
Arm group label:
Group II, Arm 4 (VTC400, IVADo, IVA regimens)
Other name:
EC
Intervention type:
Drug
Intervention name:
Ifosfamide
Description:
Given IV
Arm group label:
Group II, Arm 3 (VTC400, IVADo, VTC250, VAC1200 regimens)
Arm group label:
Group II, Arm 4 (VTC400, IVADo, IVA regimens)
Other name:
Asta Z 4942
Other name:
Asta Z-4942
Other name:
Cyfos
Other name:
Holoxan
Other name:
Holoxane
Other name:
Ifex
Other name:
IFO
Other name:
IFO-Cell
Other name:
Ifolem
Other name:
Ifomida
Other name:
Ifomide
Other name:
Ifosfamidum
Other name:
Ifoxan
Other name:
IFX
Other name:
Iphosphamid
Other name:
Iphosphamide
Other name:
Iso-Endoxan
Other name:
Isoendoxan
Other name:
Isophosphamide
Other name:
Mitoxana
Other name:
MJF 9325
Other name:
MJF-9325
Other name:
Naxamide
Other name:
Seromida
Other name:
Tronoxal
Other name:
Z 4942
Other name:
Z-4942
Intervention type:
Procedure
Intervention name:
Magnetic Resonance Imaging
Description:
Undergo MRI
Arm group label:
Group II, Arm 3 (VTC400, IVADo, VTC250, VAC1200 regimens)
Arm group label:
Group II, Arm 4 (VTC400, IVADo, IVA regimens)
Other name:
Magnetic Resonance
Other name:
Magnetic Resonance Imaging (MRI)
Other name:
Magnetic resonance imaging (procedure)
Other name:
Magnetic Resonance Imaging Scan
Other name:
Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance
Other name:
MR
Other name:
MR Imaging
Other name:
MRI
Other name:
MRI Scan
Other name:
MRIs
Other name:
NMR Imaging
Other name:
NMRI
Other name:
Nuclear Magnetic Resonance Imaging
Other name:
sMRI
Other name:
Structural MRI
Intervention type:
Procedure
Intervention name:
Multigated Acquisition Scan
Description:
Undergo MUGA
Arm group label:
Group II, Arm 3 (VTC400, IVADo, VTC250, VAC1200 regimens)
Arm group label:
Group II, Arm 4 (VTC400, IVADo, IVA regimens)
Other name:
Blood Pool Scan
Other name:
Equilibrium Radionuclide Angiography
Other name:
Gated Blood Pool Imaging
Other name:
Gated Heart Pool Scan
Other name:
MUGA
Other name:
MUGA Scan
Other name:
Multi-Gated Acquisition Scan
Other name:
Radionuclide Ventriculogram Scan
Other name:
Radionuclide Ventriculography
Other name:
RNV Scan
Other name:
RNVG
Other name:
SYMA Scanning
Other name:
Synchronized Multigated Acquisition Scanning
Intervention type:
Other
Intervention name:
Patient Observation
Description:
Undergo observation
Arm group label:
Group I, Arm 2 (observation)
Other name:
Active Surveillance
Other name:
deferred therapy
Other name:
expectant management
Other name:
Observation
Other name:
Watchful Waiting
Intervention type:
Procedure
Intervention name:
Positron Emission Tomography
Description:
Undergo PET
Arm group label:
Group II, Arm 3 (VTC400, IVADo, VTC250, VAC1200 regimens)
Arm group label:
Group II, Arm 4 (VTC400, IVADo, IVA regimens)
Other name:
Medical Imaging, Positron Emission Tomography
Other name:
PET
Other name:
PET Scan
Other name:
Positron emission tomography (procedure)
Other name:
Positron Emission Tomography Scan
Other name:
Positron-Emission Tomography
Other name:
proton magnetic resonance spectroscopic imaging
Other name:
PT
Intervention type:
Procedure
Intervention name:
Resection
Description:
Undergo surgery
Arm group label:
Group I, Arm 1 (VAC1200/VA regimen)
Arm group label:
Group I, Arm 2 (observation)
Arm group label:
Group II, Arm 3 (VTC400, IVADo, VTC250, VAC1200 regimens)
Arm group label:
Group II, Arm 4 (VTC400, IVADo, IVA regimens)
Other name:
Surgical Resection
Intervention type:
Drug
Intervention name:
Topotecan
Description:
Given IV
Arm group label:
Group II, Arm 3 (VTC400, IVADo, VTC250, VAC1200 regimens)
Arm group label:
Group II, Arm 4 (VTC400, IVADo, IVA regimens)
Other name:
Hycamptamine
Other name:
Topotecan Lactone
Intervention type:
Procedure
Intervention name:
Ultrasound Imaging
Description:
Undergo ultrasound
Arm group label:
Group I, Arm 1 (VAC1200/VA regimen)
Other name:
2-Dimensional Grayscale Ultrasound Imaging
Other name:
2-Dimensional Ultrasound Imaging
Other name:
2D-US
Other name:
Ultrasonography
Other name:
Ultrasound
Other name:
Ultrasound Test
Other name:
Ultrasound, Medical
Other name:
US
Intervention type:
Drug
Intervention name:
Vincristine
Description:
Given IV
Arm group label:
Group I, Arm 1 (VAC1200/VA regimen)
Arm group label:
Group II, Arm 3 (VTC400, IVADo, VTC250, VAC1200 regimens)
Arm group label:
Group II, Arm 4 (VTC400, IVADo, IVA regimens)
Other name:
LCR
Other name:
Leurocristine
Other name:
VCR
Other name:
Vincrystine
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.
Detailed description:
PRIMARY OBJECTIVE:
I. 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:
I. 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:
I. 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.
V. 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.
GROUP I (TYPE I/Ir PPB): Patients undergo surgery on study. Patients < 5 years old 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.
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.
Criteria for eligibility:
Criteria:
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/gender 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
- 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
Gender:
All
Minimum age:
N/A
Maximum age:
21 Years
Healthy volunteers:
No
Start date:
December 17, 2024
Completion date:
March 31, 2029
Lead sponsor:
Agency:
Children's Oncology Group
Agency class:
Other
Source:
Children's Oncology Group
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06647953
