Ignite Creation Date:
2024-10-26 @ 3:43 PM
Last Modification Date:
2024-10-26 @ 3:43 PM
Study NCT ID:
NCT06647953
Status:
NOT_YET_RECRUITING
Last Update Posted:
None
First Post:
2024-10-10
Brief 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
Sponsor:
None
Organization:
None
Study Overview
Official Title:
Prospective Treatment of Types I II and III Pleuropulmonary Blastoma PPB
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-10
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
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 cells deoxyribonucleic acid DNA and may kill tumor cells Doxorubicin is in a class of medications called anthracyclines Doxorubicin damages the cells 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
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 cells deoxyribonucleic acid DNA and may kill tumor cells Doxorubicin is in a class of medications called anthracyclines Doxorubicin damages the cells 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 geneticsepigenetics 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 IIr 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 VAC1200VA 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 IIIII 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
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 geneticsepigenetics 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 IIr 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 VAC1200VA 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 IIIII 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
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None